<filename>vignettes/iEN.bib
@article{hercus_2009,
title = {The granulocyte-macrophage colony-stimulating factor receptor: linking its structure to cell signaling and its role in disease.},
author = {Hercus, <NAME> and <NAME> and Guthridge, <NAME> and Ekert, <NAME> and King-Scott, Jack and Parker, <NAME> and Lopez, <NAME>},
pages = {1289-1298},
url = {http://dx.doi.org/10.1182/blood-2008-12-164004},
year = {2009},
month = {aug},
day = {13},
urldate = {2018-10-23},
journal = {Blood},
volume = {114},
number = {7},
doi = {10.1182/blood-2008-12-164004},
pmid = {19436055},
pmcid = {PMC2727416},
abstract = {Already 20 years have passed since the cloning of the granulocyte-macrophage colony-stimulating factor ({GM}-{CSF}) receptor alpha-chain, the first member of the {GM}-{CSF}/interleukin ({IL})-3/{IL}-5 family of hemopoietic cytokine receptors to be molecularly characterized. The intervening 2 decades have uncovered a plethora of biologic functions transduced by the {GM}-{CSF} receptor (pleiotropy) and revealed distinct signaling networks that couple the receptor to biologic outcomes. Unlike other hemopoietin receptors, the {GM}-{CSF} receptor has a significant nonredundant role in myeloid hematologic malignancies, macrophage-mediated acute and chronic inflammation, pulmonary homeostasis, and allergic disease. The molecular mechanisms underlying {GM}-{CSF} receptor activation have recently been revealed by the crystal structure of the {GM}-{CSF} receptor complexed to {GM}-{CSF}, which shows an unexpected higher order assembly. Emerging evidence also suggests the existence of intracellular signosomes that are recruited in a concentration-dependent fashion to selectively control cell survival, proliferation, and differentiation by {GM}-{CSF}. These findings begin to unravel the mystery of cytokine receptor pleiotropy and are likely to also apply to the related {IL}-3 and {IL}-5 receptors as well as other heterodimeric cytokine receptors. The new insights in {GM}-{CSF} receptor activation have clinical significance as the structural and signaling nuances can be harnessed for the development of new treatments for malignant and inflammatory diseases.}
}
@article{gaudillire_2014,
title = {Clinical recovery from surgery correlates with single-cell immune signatures.},
author = {Gaudillière, <NAME> Fragiadakis, <NAME> and Bruggner, <NAME> and Nicolau, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME> Goodman, <NAME> and Davis, <NAME> and Bendall, <NAME> and Fantl, <NAME> and Angst, <NAME> and Nolan, <NAME>},
pages = {255ra131},
url = {http://dx.doi.org/10.1126/scitranslmed.3009701},
year = {2014},
month = {sep},
day = {24},
urldate = {2018-10-23},
journal = {Sci Transl Med},
volume = {6},
number = {255},
doi = {10.1126/scitranslmed.3009701},
pmid = {25253674},
pmcid = {PMC4334126},
abstract = {Delayed recovery from surgery causes personal suffering and substantial societal and economic costs. Whether immune mechanisms determine recovery after surgical trauma remains ill-defined. Single-cell mass cytometry was applied to serial whole-blood samples from 32 patients undergoing hip replacement to comprehensively characterize the phenotypic and functional immune response to surgical trauma. The simultaneous analysis of 14,000 phosphorylation events in precisely phenotyped immune cell subsets revealed uniform signaling responses among patients, demarcating a surgical immune signature. When regressed against clinical parameters of surgical recovery, including functional impairment and pain, strong correlations were found with {STAT3} (signal transducer and activator of transcription), {CREB} (adenosine 3',5'-monophosphate response element-binding protein), and {NF}-{\kappaB} (nuclear factor {\kappaB}) signaling responses in subsets of {CD14}(+) monocytes (R = 0.7 to 0.8, false discovery rate \textless 0.01). These sentinel results demonstrate the capacity of mass cytometry to survey the human immune system in a relevant clinical context. The mechanistically derived immune correlates point to diagnostic signatures, and potential therapeutic targets, that could postoperatively improve patient recovery. Copyright \copyright 2014, American Association for the Advancement of Science.}
}
@article{friedman_2010,
title = {Regularization Paths for Generalized Linear Models via Coordinate Descent.},
author = {<NAME> <NAME> <NAME>},
pages = {1-22},
url = {http://dx.doi.org/10.18637/jss.v033.i01},
year = {2010},
urldate = {2019-01-25},
journal = {J Stat Softw},
volume = {33},
number = {1},
doi = {10.18637/jss.v033.i01},
pmid = {20808728},
pmcid = {PMC2929880},
abstract = {We develop fast algorithms for estimation of generalized linear models with convex penalties. The models include linear regression, two-class logistic regression, and multinomial regression problems while the penalties include ℓ(1) (the lasso), ℓ(2) (ridge regression) and mixtures of the two (the elastic net). The algorithms use cyclical coordinate descent, computed along a regularization path. The methods can handle large problems and can also deal efficiently with sparse features. In comparative timings we find that the new algorithms are considerably faster than competing methods.}
}
@article{bendall_2011,
title = {Single-cell mass cytometry of differential immune and drug responses across a human hematopoietic continuum.},
author = {<NAME>, <NAME>, <NAME> <NAME> and Finck, <NAME> Bruggner, <NAME> and Melamed, <NAME>, <NAME>, <NAME>, <NAME>, <NAME> Sachs, <NAME>, <NAME>, <NAME> and Nolan, <NAME>},
pages = {687-696},
url = {http://dx.doi.org/10.1126/science.1198704},
year = {2011},
month = {may},
day = {6},
urldate = {2018-11-08},
journal = {Science},
volume = {332},
number = {6030},
issn = {1095-9203},
doi = {10.1126/science.1198704},
pmid = {21551058},
pmcid = {PMC3273988},
abstract = {Flow cytometry is an essential tool for dissecting the functional complexity of hematopoiesis. We used single-cell "mass cytometry" to examine healthy human bone marrow, measuring 34 parameters simultaneously in single cells (binding of 31 antibodies, viability, {DNA} content, and relative cell size). The signaling behavior of cell subsets spanning a defined hematopoietic hierarchy was monitored with 18 simultaneous markers of functional signaling states perturbed by a set of ex vivo stimuli and inhibitors. The data set allowed for an algorithmically driven assembly of related cell types defined by surface antigen expression, providing a superimposable map of cell signaling responses in combination with drug inhibition. Visualized in this manner, the analysis revealed previously unappreciated instances of both precise signaling responses that were bounded within conventionally defined cell subsets and more continuous phosphorylation responses that crossed cell population boundaries in unexpected manners yet tracked closely with cellular phenotype. Collectively, such single-cell analyses provide system-wide views of immune signaling in healthy human hematopoiesis, against which drug action and disease can be compared for mechanistic studies and pharmacologic intervention.}
}
@article{ivashkiv_2014,
title = {Regulation of type I interferon responses.},
author = {Ivashkiv, <NAME> and Donlin, <NAME>},
pages = {36-49},
url = {http://dx.doi.org/10.1038/nri3581},
year = {2014},
month = {jan},
urldate = {2018-10-22},
journal = {Nat Rev Immunol},
volume = {14},
number = {1},
doi = {10.1038/nri3581},
pmid = {24362405},
pmcid = {PMC4084561},
abstract = {Type I interferons ({IFNs}) activate intracellular antimicrobial programmes and influence the development of innate and adaptive immune responses. Canonical type I {IFN} signalling activates the Janus kinase ({JAK})-signal transducer and activator of transcription ({STAT}) pathway, leading to transcription of {IFN}-stimulated genes ({ISGs}). Host, pathogen and environmental factors regulate the responses of cells to this signalling pathway and thus calibrate host defences while limiting tissue damage and preventing autoimmunity. Here, we summarize the signalling and epigenetic mechanisms that regulate type I {IFN}-induced {STAT} activation and {ISG} transcription and translation. These regulatory mechanisms determine the biological outcomes of type I {IFN} responses and whether pathogens are cleared effectively or chronic infection or autoimmune disease ensues.}
}
@article{malek_2010,
title = {Interleukin-2 receptor signaling: at the interface between tolerance and immunity.},
author = {<NAME> and <NAME>},
pages = {153-165},
url = {http://dx.doi.org/10.1016/j.immuni.2010.08.004},
year = {2010},
month = {aug},
day = {27},
urldate = {2018-10-23},
journal = {Immunity},
volume = {33},
number = {2},
doi = {10.1016/j.immuni.2010.08.004},
pmid = {20732639},
pmcid = {PMC2946796},
abstract = {Interleukin-2 receptor ({IL}-{2R}) signaling regulates tolerance and immunity. Here, we review recent work concerning the structure, signaling, and function of the {IL}-{2R}, emphasizing the contribution of {IL}-2 for T cell-dependent activity in vivo. {IL}-{2R} signaling influences two discrete aspects of immune responses by {CD8}(+) T cells, terminal differentiation of effector cells in primary responses, and aspects of memory recall responses. {IL}-2 also delivers essential signals for thymic development of regulatory T (Treg) cells and later to promote their homeostasis and function. Each of these outcomes on T effector and Treg cells requires distinct amounts of {IL}-{2R} signaling, with low {IL}-{2R} signaling sufficient for many key aspects of Treg cells. Thus, tolerance is readily maintained and favored with limited {IL}-2. Copyright 2010 Elsevier Inc. All rights reserved.}
}
@book{efron_1994,
title = {An Introduction to the Bootstrap},
author = {<NAME> Tibshirani, <NAME>.},
series = {Chapman \& Hall/{CRC} Monographs on Statistics \& Applied Probability},
publisher = {Chapman and Hall/{CRC}},
url = {http://link.springer.com/10.1007/978-1-4899-4541-9},
year = {1994},
urldate = {2018-10-16},
isbn = {978-0-412-04231-7},
doi = {10.1007/978-1-4899-4541-9},
address = {Boca Raton},
abstract = {Statistics is a subject of many uses and surprisingly few effective practitioners. The traditional road to statistical knowledge is blocked, for most, by a formidable wall of mathematics. The approach in An Introduction to the Bootstrap avoids that wall. It arms scientists and engineers, as well as statisticians, with the computational techniques they need to analyze and understand complicated data sets.}
}
@article{bandura_2009,
title = {Mass cytometry: technique for real time single cell multitarget immunoassay based on inductively coupled plasma time-of-flight mass spectrometry.},
author = {Bandura, <NAME> and Baranov, <NAME> and Ornatsky, <NAME> and Antonov, Alexei and Kinach, <NAME>, Xudong and Pavlov, Serguei and Vorobiev, Sergey and Dick, <NAME> and Tanner, <NAME>},
pages = {6813-6822},
url = {http://dx.doi.org/10.1021/ac901049w},
year = {2009},
month = {aug},
day = {15},
urldate = {2018-11-07},
journal = {Anal Chem},
volume = {81},
number = {16},
doi = {10.1021/ac901049w},
pmid = {19601617},
abstract = {A novel instrument for real time analysis of individual biological cells or other microparticles is described. The instrument is based on inductively coupled plasma time-of-flight mass spectrometry and comprises a three-aperture plasma-vacuum interface, a dc quadrupole turning optics for decoupling ions from neutral components, an rf quadrupole ion guide discriminating against low-mass dominant plasma ions, a point-to-parallel focusing dc quadrupole doublet, an orthogonal acceleration reflectron analyzer, a discrete dynode fast ion detector, and an 8-bit 1 {GHz} digitizer. A high spectrum generation frequency of 76.8 {kHz} provides capability for collecting multiple spectra from each particle-induced transient ion cloud, typically of 200-300 micros duration. It is shown that the transients can be resolved and characterized individually at a peak frequency of 1100 particles per second. Design considerations and optimization data are presented. The figures of merit of the instrument are measured under standard inductively coupled plasma ({ICP}) operating conditions (\textless3\% cerium oxide ratio). At mass resolution (full width at half-maximum) M/{DeltaM} \textgreater 900 for m/z = 159, the sensitivity with a standard sample introduction system of \textgreater1.4 x 10(8) ion counts per second per mg L(-1) of Tb and an abundance sensitivity of (6 x 10(-4))-(1.4 x 10(-3)) (trailing and leading masses, respectively) are shown. The mass range (m/z = 125-215) and abundance sensitivity are sufficient for elemental immunoassay with up to 60 distinct available elemental tags. When \textless15 elemental tags are used, a higher sensitivity mode at lower resolution (M/{DeltaM} \textgreater 500) can be used, which provides \textgreater2.4 x 10(8) cps per mg L(-1) of Tb, at (1.5 x 10(-3))-(5.0 x 10(-3)) abundance sensitivity. The real-time simultaneous detection of multiple isotopes from individual 1.8 microm polystyrene beads labeled with lanthanides is shown. A real time single cell 20 antigen expression assay of model cell lines and leukemia patient samples immuno-labeled with lanthanide-tagged antibodies is presented.}
}
@article{finck_2013,
title = {Normalization of mass cytometry data with bead standards.},
author = {<NAME> Simonds, <NAME> Jager, <NAME> Krishnaswamy, <NAME>, <NAME> <NAME>, <NAME>, <NAME>, <NAME>},
pages = {483-494},
url = {http://dx.doi.org/10.1002/cyto.a.22271},
year = {2013},
month = {may},
urldate = {2017-07-24},
journal = {Cytometry A},
volume = {83},
number = {5},
doi = {10.1002/cyto.a.22271},
pmid = {23512433},
pmcid = {PMC3688049},
f1000-projects = {immuEN},
abstract = {Mass cytometry uses atomic mass spectrometry combined with isotopically pure reporter elements to currently measure as many as 40 parameters per single cell. As with any quantitative technology, there is a fundamental need for quality assurance and normalization protocols. In the case of mass cytometry, the signal variation over time due to changes in instrument performance combined with intervals between scheduled maintenance must be accounted for and then normalized. Here, samples were mixed with polystyrene beads embedded with metal lanthanides, allowing monitoring of mass cytometry instrument performance over multiple days of data acquisition. The protocol described here includes simultaneous measurements of beads and cells on the mass cytometer, subsequent extraction of the bead-based signature, and the application of an algorithm enabling correction of both short- and long-term signal fluctuations. The variation in the intensity of the beads that remains after normalization may also be used to determine data quality. Application of the algorithm to a one-month longitudinal analysis of a human peripheral blood sample reduced the range of median signal fluctuation from 4.9-fold to 1.3-fold. Copyright \copyright 2013 International Society for Advancement of Cytometry.}
}
@article{zunder_2015,
title = {Palladium-based mass tag cell barcoding with a doublet-filtering scheme and single-cell deconvolution algorithm.},
author = {Zunder, <NAME> Finck, <NAME>, <NAME>, <NAME> Krishnaswamy, <NAME>, <NAME>, <NAME> Bjornson, <NAME>, <NAME> and Bodenmiller, <NAME>, <NAME>, <NAME>, <NAME>},
pages = {316-333},
url = {http://dx.doi.org/10.1038/nprot.2015.020},
year = {2015},
month = {feb},
urldate = {2017-07-24},
journal = {Nat Protoc},
volume = {10},
number = {2},
doi = {10.1038/nprot.2015.020},
pmid = {25612231},
pmcid = {PMC4347881},
f1000-projects = {immuEN},
abstract = {Mass-tag cell barcoding ({MCB}) labels individual cell samples with unique combinatorial barcodes, after which they are pooled for processing and measurement as a single multiplexed sample. The {MCB} method eliminates variability between samples in antibody staining and instrument sensitivity, reduces antibody consumption and shortens instrument measurement time. Here we present an optimized {MCB} protocol. The use of palladium-based labeling reagents expands the number of measurement channels available for mass cytometry and reduces interference with lanthanide-based antibody measurement. An error-detecting combinatorial barcoding scheme allows cell doublets to be identified and removed from the analysis. A debarcoding algorithm that is single cell-based rather than population-based improves the accuracy and efficiency of sample deconvolution. This debarcoding algorithm has been packaged into software that allows rapid and unbiased sample deconvolution. The {MCB} procedure takes 3-4 h, not including sample acquisition time of ∼1 h per million cells.}
}
@article{krutzik_2003,
title = {Intracellular phospho-protein staining techniques for flow cytometry: monitoring single cell signaling events.},
author = {Krutzik, <NAME> and Nolan, <NAME>},
pages = {61-70},
url = {http://dx.doi.org/10.1002/cyto.a.10072},
year = {2003},
month = {oct},
urldate = {2018-08-15},
journal = {Cytometry A},
volume = {55},
number = {2},
doi = {10.1002/cyto.a.10072},
pmid = {14505311},
f1000-projects = {immuEN},
abstract = {{BACKGROUND}: Recent advances in intracellular staining techniques, cytometer technology, fluorescent reagents, and antibody production have expanded the number of intracellular antigens that can be analyzed by flow cytometry. Measurement of protein phosphorylation with phospho-specific antibodies has given insight into kinase signaling cascades. However, available techniques for phospho-epitope staining can differ greatly, making it necessary to understand the differences between the outcomes when such techniques are applied and to develop robust and reproducible methods of application. {METHODS}: Ten different cellular fixation and permeabilization techniques were tested for their ability to provide phospho-specific staining. Combinations of formaldehyde, methanol, ethanol, acetone, Triton X-100, and saponin were used as fixation and permeabilization reagents. Phospho-specific antibodies were labeled with Alexa Fluor dyes to provide multicolor analysis of different signaling events simultaneously within individual cells. {RESULTS}: Fixing cells with 1.5\% formaldehyde followed by permeabilization in methanol gave optimal results for {pERK}, pp38, {pJNK}, {pStat1}, {pStat5}, and {pStat6} staining. Alteration of formaldehyde fixation and methanol permeabilization times affected measurements of phosphorylation induction. Phospho-specific flow cytometric analyses correlated well with Western blotting, providing cross platform validation of the technique. {CONCLUSIONS}: Measuring phosphorylation events by flow cytometry provides a rapid and efficient way to measure kinase cascades in individual cells. Stability of phospho-epitopes in methanol allows long-term storage of samples prior to analysis. Multiple signaling cascades can be monitored simultaneously through the use of different fluorophore labels to determine specificity of ligands or inhibitors. Application of optimized techniques to heterogeneous cell types such as peripheral blood or murine splenocytes may allow signaling to be analyzed simultaneously in immune cell subsets. Copyright 2003 Wiley-Liss, Inc.}
}
@article{hanley_1982,
title = {The meaning and use of the area under a receiver operating characteristic ({ROC}) curve.},
author = {<NAME> and {McNeil}, <NAME>},
pages = {29-36},
url = {http://dx.doi.org/10.1148/radiology.143.1.7063747},
year = {1982},
month = {apr},
urldate = {2018-08-16},
journal = {Radiology},
volume = {143},
number = {1},
doi = {10.1148/radiology.143.1.7063747},
pmid = {7063747},
f1000-projects = {immuEN},
abstract = {A representation and interpretation of the area under a receiver operating characteristic ({ROC}) curve obtained by the "rating" method, or by mathematical predictions based on patient characteristics, is presented. It is shown that in such a setting the area represents the probability that a randomly chosen diseased subject is (correctly) rated or ranked with greater suspicion than a randomly chosen non-diseased subject. Moreover, this probability of a correct ranking is the same quantity that is estimated by the already well-studied nonparametric Wilcoxon statistic. These two relationships are exploited to (a) provide rapid closed-form expressions for the approximate magnitude of the sampling variability, i.e., standard error that one uses to accompany the area under a smoothed {ROC} curve, (b) guide in determining the size of the sample required to provide a sufficiently reliable estimate of this area, and (c) determine how large sample sizes should be to ensure that one can statistically detect differences in the accuracy of diagnostic techniques.}
}
@article{gaudillire_2015,
title = {Implementing Mass Cytometry at the Bedside to Study the Immunological Basis of Human Diseases: Distinctive Immune Features in Patients with a History of Term or Preterm Birth.},
author = {<NAME>, <NAME>, <NAME>, <NAME> Fragiadakis, <NAME>, <NAME> Aghaeepour, <NAME>, <NAME>, Cele and El-Sayed, <NAME>, <NAME> and Lewis, <NAME> and Stevenson, <NAME> and Nolan, <NAME> and Angst, <NAME>},
pages = {817-829},
url = {http://dx.doi.org/10.1002/cyto.a.22720},
year = {2015},
month = {sep},
urldate = {2018-08-16},
journal = {Cytometry A},
volume = {87},
number = {9},
doi = {10.1002/cyto.a.22720},
pmid = {26190063},
pmcid = {PMC4758855},
f1000-projects = {immuEN},
abstract = {Single-cell technologies have immense potential to shed light on molecular and biological processes that drive human diseases. Mass cytometry (or Cytometry by Time Of Flight mass spectrometry, {CyTOF}) has already been employed in clinical studies to comprehensively survey patients' circulating immune system. As interest in the "bedside" application of mass cytometry is growing, the delineation of relevant methodological issues is called for. This report uses a newly generated dataset to discuss important methodological considerations when mass cytometry is implemented in a clinical study. Specifically, the use of whole blood samples versus peripheral blood mononuclear cells ({PBMCs}), design of mass-tagged antibody panels, technical and analytical implications of sample barcoding, and application of traditional and unsupervised approaches to analyze high-dimensional mass cytometry datasets are discussed. A mass cytometry assay was implemented in a cross-sectional study of 19 women with a history of term or preterm birth to determine whether immune traits in peripheral blood differentiate the two groups in the absence of pregnancy. Twenty-seven phenotypic and 11 intracellular markers were simultaneously analyzed in whole blood samples stimulated with lipopolysaccharide ({LPS} at 0, 0.1, 1, 10, and 100 ng {mL}(-1)) to examine dose-dependent signaling responses within the toll-like receptor 4 ({TLR4}) pathway. Complementary analyses, grounded in traditional or unsupervised gating strategies of immune cell subsets, indicated that the {prpS6} and {pMAPKAPK2} responses in classical monocytes are accentuated in women with a history of preterm birth ({FDR\textless} 1\%). The results suggest that women predisposed to preterm birth may be prone to mount an exacerbated {TLR4} response during the course of pregnancy. This important hypothesis-generating finding points to the power of single-cell mass cytometry to detect biologically important differences in a relatively small patient cohort. \copyright 2015 International Society for Advancement of Cytometry.}
}
@article{porter_2011,
title = {Chimeric antigen receptor-modified T cells in chronic lymphoid leukemia.},
author = {Porter, <NAME> and Levine, <NAME> and Kalos, <NAME> Bagg, <NAME>, <NAME>},
pages = {725-733},
url = {http://dx.doi.org/10.1056/{NEJMoa1103849}},
year = {2011},
month = {aug},
day = {25},
urldate = {2019-02-05},
journal = {N Engl J Med},
volume = {365},
number = {8},
issn = {1533-4406},
doi = {10.1056/{NEJMoa1103849}},
pmid = {21830940},
pmcid = {PMC3387277},
abstract = {We designed a lentiviral vector expressing a chimeric antigen receptor with specificity for the B-cell antigen {CD19}, coupled with {CD137} (a costimulatory receptor in T cells [4-{1BB}]) and {CD3}-zeta (a signal-transduction component of the T-cell antigen receptor) signaling domains. A low dose (approximately 1.5×10(5) cells per kilogram of body weight) of autologous chimeric antigen receptor-modified T cells reinfused into a patient with refractory chronic lymphocytic leukemia ({CLL}) expanded to a level that was more than 1000 times as high as the initial engraftment level in vivo, with delayed development of the tumor lysis syndrome and with complete remission. Apart from the tumor lysis syndrome, the only other grade 3/4 toxic effect related to chimeric antigen receptor T cells was lymphopenia. Engineered cells persisted at high levels for 6 months in the blood and bone marrow and continued to express the chimeric antigen receptor. A specific immune response was detected in the bone marrow, accompanied by loss of normal B cells and leukemia cells that express {CD19}. Remission was ongoing 10 months after treatment. Hypogammaglobulinemia was an expected chronic toxic effect.}
}
@book{vapnik_2000,
title = {The Nature of Statistical Learning Theory},
author = {Vapnik, <NAME>.},
publisher = {Springer New York},
url = {http://link.springer.com/10.1007/978-1-4757-3264-1},
year = {2000},
urldate = {2018-11-26},
isbn = {978-1-4419-3160-3},
doi = {10.1007/978-1-4757-3264-1},
address = {New York, {NY}},
abstract = {Setting of the learning problem consistency of learning processes bounds on the rate of convergence of learning processes controlling the generalization ability of learning processes constructing learning algorithms what is important in learning theory?.}
}
@article{arck_2013,
title = {Fetomaternal immune cross-talk and its consequences for maternal and offspring's health.},
author = {<NAME> and <NAME>},
pages = {548-556},
url = {http://dx.doi.org/10.1038/nm.3160},
year = {2013},
month = {may},
day = {7},
urldate = {2018-12-05},
journal = {Nat Med},
volume = {19},
number = {5},
doi = {10.1038/nm.3160},
pmid = {23652115},
abstract = {An improved mechanistic understanding of the adaptational processes mounted during mammalian reproduction is emerging. Intricate pathways occurring at the fetomaternal interface, such as the formation of a functional synapse between invading fetal trophoblast cells, and the involvement of various maternal immune cell subsets and epigenetically modified decidual stromal cells have now been identified. These complex pathways synergistically create a tolerogenic niche in which the semiallogeneic fetus can develop. New insights into fetomaternal immune cross-talk may help us to understand the pathogenesis of pregnancy complications as well as poor postnatal health. Moreover, the effects of maternal immune adaptation to pregnancy on autoimmune disease activity are becoming increasingly evident. Thus, insights into fetomaternal immune cross-talk not only advance our understanding of pregnancy-related complications but also may be informative on how immune tolerance can be modulated in clinical settings outside the context of reproduction.}
}
@article{romero_2014,
title = {Preterm labor: one syndrome, many causes.},
author = {<NAME> <NAME>},
pages = {760-765},
url = {http://dx.doi.org/10.1126/science.1251816},
year = {2014},
month = {aug},
day = {15},
urldate = {2018-12-05},
journal = {Science},
volume = {345},
number = {6198},
doi = {10.1126/science.1251816},
pmid = {25124429},
pmcid = {PMC4191866},
abstract = {Preterm birth is associated with 5 to 18\% of pregnancies and is a leading cause of infant morbidity and mortality. Spontaneous preterm labor, a syndrome caused by multiple pathologic processes, leads to 70\% of preterm births. The prevention and the treatment of preterm labor have been long-standing challenges. We summarize the current understanding of the mechanisms of disease implicated in this condition and review advances relevant to intra-amniotic infection, decidual senescence, and breakdown of maternal-fetal tolerance. The success of progestogen treatment to prevent preterm birth in a subset of patients at risk is a cause for optimism. Solving the mystery of preterm labor, which compromises the health of future generations, is a formidable scientific challenge worthy of investment. Copyright \copyright 2014, American Association for the Advancement of Science.}
}
@article{lu_2008,
title = {{LPS}/{TLR4} signal transduction pathway.},
author = {<NAME> and <NAME> and <NAME>},
pages = {145-151},
url = {http://dx.doi.org/10.1016/j.cyto.2008.01.006},
year = {2008},
month = {may},
urldate = {2018-10-22},
journal = {Cytokine},
volume = {42},
number = {2},
doi = {10.1016/j.cyto.2008.01.006},
pmid = {18304834},
abstract = {The stimulation of Toll-like receptor 4 ({TLR4}) by lipopolysaccharide ({LPS}) induces the release of critical proinflammatory cytokines that are necessary to activate potent immune responses. {LPS}/{TLR4} signaling has been intensively studied in the past few years. Here we review molecules involved in {TLR4}-mediated signaling, including players that are involved in the negative regulation of this important pathway.}
}
@article{beutler_2009,
title = {{TLRs} and innate immunity.},
author = {Beutler, <NAME>},
pages = {1399-1407},
url = {http://dx.doi.org/10.1182/blood-2008-07-019307},
year = {2009},
month = {feb},
day = {12},
urldate = {2019-03-15},
journal = {Blood},
volume = {113},
number = {7},
doi = {10.1182/blood-2008-07-019307},
pmid = {18757776},
pmcid = {PMC2644070},
abstract = {One of the most fundamental questions in immunology pertains to the recognition of non-self, which for the most part means microbes. How do we initially realize that we have been inoculated with microbes, and how is the immune response ignited? Genetic studies have made important inroads into this question during the past decade, and we now know that in mammals, a relatively small number of receptors operate to detect signature molecules that herald infection. One or more of these signature molecules are displayed by almost all microbes. These receptors and the signals they initiate have been studied in depth by random germline mutagenesis and positional cloning (forward genetics). Herein is a concise description of what has been learned about the Toll-like receptors, which play an essential part in the perception of microbes and shape the complex host responses that occur during infection.}
}
@article{sabio_2014,
title = {{TNF} and {MAP} kinase signalling pathways.},
author = {<NAME> and <NAME>},
pages = {237-245},
url = {http://dx.doi.org/10.1016/j.smim.2014.02.009},
year = {2014},
month = {jun},
urldate = {2018-10-22},
journal = {Semin Immunol},
volume = {26},
number = {3},
doi = {10.1016/j.smim.2014.02.009},
pmid = {24647229},
pmcid = {PMC4099309},
abstract = {The binding of tumour necrosis factor \alpha ({TNF\alpha}) to cell surface receptors engages multiple signal transduction pathways, including three groups of mitogen-activated protein ({MAP}) kinases: extracellular-signal-regulated kinases ({ERKs}); the {cJun} {NH2}-terminal kinases ({JNKs}); and the p38 {MAP} kinases. These {MAP} kinase signalling pathways induce a secondary response by increasing the expression of several inflammatory cytokines (including {TNF\alpha}) that contribute to the biological activity of {TNF\alpha}. {MAP} kinases therefore function both upstream and down-stream of signalling by {TNF\alpha} receptors. Here we review mechanisms that mediate these actions of {MAP} kinases during the response to {TNF\alpha}. Copyright \copyright 2014 Elsevier Ltd. All rights reserved.}
}
@article{heinrich_2003,
title = {Principles of interleukin ({IL})-6-type cytokine signalling and its regulation.},
author = {<NAME> and Behrmann, <NAME> Haan, <NAME>, <NAME>, <NAME>, Fred},
pages = {1-20},
url = {http://dx.doi.org/10.1042/{BJ20030407}},
year = {2003},
month = {aug},
day = {15},
urldate = {2018-10-23},
journal = {Biochem J},
volume = {374},
number = {Pt 1},
doi = {10.1042/{BJ20030407}},
pmid = {12773095},
pmcid = {PMC1223585},
abstract = {The {IL} (interleukin)-6-type cytokines {IL}-6, {IL}-11, {LIF} (leukaemia inhibitory factor), {OSM} (oncostatin M), ciliary neurotrophic factor, cardiotrophin-1 and cardiotrophin-like cytokine are an important family of mediators involved in the regulation of the acute-phase response to injury and infection. Besides their functions in inflammation and the immune response, these cytokines play also a crucial role in haematopoiesis, liver and neuronal regeneration, embryonal development and fertility. Dysregulation of {IL}-6-type cytokine signalling contributes to the onset and maintenance of several diseases, such as rheumatoid arthritis, inflammatory bowel disease, osteoporosis, multiple sclerosis and various types of cancer (e.g. multiple myeloma and prostate cancer). {IL}-6-type cytokines exert their action via the signal transducers gp (glycoprotein) 130, {LIF} receptor and {OSM} receptor leading to the activation of the {JAK}/{STAT} (Janus kinase/signal transducer and activator of transcription) and {MAPK} (mitogen-activated protein kinase) cascades. This review focuses on recent progress in the understanding of the molecular mechanisms of {IL}-6-type cytokine signal transduction. Emphasis is put on the termination and modulation of the {JAK}/{STAT} signalling pathway mediated by tyrosine phosphatases, the {SOCS} (suppressor of cytokine signalling) feedback inhibitors and {PIAS} (protein inhibitor of activated {STAT}) proteins. Also the cross-talk between the {JAK}/{STAT} pathway with other signalling cascades is discussed.}
}
@article{finak_2016,
title = {Standardizing Flow Cytometry Immunophenotyping Analysis from the Human {ImmunoPhenotyping} Consortium.},
author = {Finak, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME> Devine, <NAME>, Gerlinde and Pekalski, <NAME> and Pontikos, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME> and Brandes, Aaron and Ramey, John and Aghaeepour, Nima and Mosmann, Tim and Scheuermann, <NAME> and Reed, Elaine and Palucka, Karolina and Pascual, Virginia and Blomberg, <NAME> and Nestle, <NAME>, <NAME> and Brinkman, <NAME> and Gottardo, Raphael and Maecker, Holden and {McCoy}, J Philip},
pages = {20686},
url = {http://dx.doi.org/10.1038/srep20686},
year = {2016},
month = {feb},
day = {10},
urldate = {2018-11-07},
journal = {Sci Rep},
volume = {6},
doi = {10.1038/srep20686},
pmid = {26861911},
pmcid = {PMC4748244},
abstract = {Standardization of immunophenotyping requires careful attention to reagents, sample handling, instrument setup, and data analysis, and is essential for successful cross-study and cross-center comparison of data. Experts developed five standardized, eight-color panels for identification of major immune cell subsets in peripheral blood. These were produced as pre-configured, lyophilized, reagents in 96-well plates. We present the results of a coordinated analysis of samples across nine laboratories using these panels with standardized operating procedures ({SOPs}). Manual gating was performed by each site and by a central site. Automated gating algorithms were developed and tested by the {FlowCAP} consortium. Centralized manual gating can reduce cross-center variability, and we sought to determine whether automated methods could streamline and standardize the analysis. Within-site variability was low in all experiments, but cross-site variability was lower when central analysis was performed in comparison with site-specific analysis. It was also lower for clearly defined cell subsets than those based on dim markers and for rare populations. Automated gating was able to match the performance of central manual analysis for all tested panels, exhibiting little to no bias and comparable variability. Standardized staining, data collection, and automated gating can increase power, reduce variability, and streamline analysis for immunophenotyping.}
}
@article{tai_2007,
title = {Incorporating prior knowledge of gene functional groups into regularized discriminant analysis of microarray data.},
author = {<NAME> and <NAME>},
pages = {3170-3177},
url = {http://dx.doi.org/10.1093/bioinformatics/btm488},
year = {2007},
month = {dec},
day = {1},
urldate = {2019-01-16},
journal = {Bioinformatics},
volume = {23},
number = {23},
doi = {10.1093/bioinformatics/btm488},
pmid = {17933851},
abstract = {{MOTIVATION}: Discriminant analysis for high-dimensional and low-sample-sized data has become a hot research topic in bioinformatics, mainly motivated by its importance and challenge in applications to tumor classifications for high-dimensional microarray data. Two of the popular methods are the nearest shrunken centroids, also called predictive analysis of microarray ({PAM}), and shrunken centroids regularized discriminant analysis ({SCRDA}). Both methods are modifications to the classic linear discriminant analysis ({LDA}) in two aspects tailored to high-dimensional and low-sample-sized data: one is the regularization of the covariance matrix, and the other is variable selection through shrinkage. In spite of their usefulness, there are potential limitations with each method. The main concern is that both {PAM} and {SCRDA} are possibly too extreme: the covariance matrix in the former is restricted to be diagonal while in the latter there is barely any restriction. Based on the biology of gene functions and given the feature of the data, it may be beneficial to estimate the covariance matrix as an intermediate between the two; furthermore, more effective shrinkage schemes may be possible. {RESULTS}: We propose modified {LDA} methods to integrate biological knowledge of gene functions (or variable groups) into classification of microarray data. Instead of simply treating all the genes independently or imposing no restriction on the correlations among the genes, we group the genes according to their biological functions extracted from existing biological knowledge or data, and propose regularized covariance estimators that encourages between-group gene independence and within-group gene correlations while maintaining the flexibility of any general covariance structure. Furthermore, we propose a shrinkage scheme on groups of genes that tends to retain or remove a whole group of the genes altogether, in contrast to the standard shrinkage on individual genes. We show that one of the proposed methods performed better than {PAM} and {SCRDA} in a simulation study and several real data examples.}
}
@article{pihlstrom_2005,
title = {Periodontal diseases.},
author = {Pihlstrom, <NAME> and Michalowicz, <NAME> and Johnson, <NAME>},
pages = {1809-1820},
url = {http://dx.doi.org/10.1016/S0140-6736(05)67728-8},
year = {2005},
month = {nov},
day = {19},
urldate = {2005-11-25},
journal = {Lancet},
volume = {366},
number = {9499},
doi = {10.1016/S0140-6736(05)67728-8},
pmid = {16298220},
abstract = {The periodontal diseases are highly prevalent and can affect up to 90\% of the worldwide population. Gingivitis, the mildest form of periodontal disease, is caused by the bacterial biofilm (dental plaque) that accumulates on teeth adjacent to the gingiva (gums). However, gingivitis does not affect the underlying supporting structures of the teeth and is reversible. Periodontitis results in loss of connective tissue and bone support and is a major cause of tooth loss in adults. In addition to pathogenic microorganisms in the biofilm, genetic and environmental factors, especially tobacco use, contribute to the cause of these diseases. Genetic, dermatological, haematological, granulomatous, immunosuppressive, and neoplastic disorders can also have periodontal manifestations. Common forms of periodontal disease have been associated with adverse pregnancy outcomes, cardiovascular disease, stroke, pulmonary disease, and diabetes, but the causal relations have not been established. Prevention and treatment are aimed at controlling the bacterial biofilm and other risk factors, arresting progressive disease, and restoring lost tooth support.}
}
@article{newell_2016,
title = {Mass cytometry: blessed with the curse of dimensionality.},
author = {Newell, <NAME> and <NAME>},
pages = {890-895},
url = {http://www.nature.com/doifinder/10.1038/ni.3485},
year = {2016},
month = {jul},
day = {19},
urldate = {2018-08-16},
journal = {Nat Immunol},
volume = {17},
number = {8},
issn = {1529-2908},
doi = {10.1038/ni.3485},
pmid = {27434000},
f1000-projects = {immuEN},
abstract = {Immunologists are being compelled to develop new high-dimensional perspectives of cellular heterogeneity and to determine which applications best exploit the power of mass cytometry and associated multiplex approaches.}
}
@article{crawford_2014,
title = {Concomitant evaluation of {PMA}+ionomycin-induced kinase phosphorylation and cytokine production in T cell subsets by flow cytometry.},
author = {Crawford, <NAME> and Jalbert, Emilie and Ndhlovu, <NAME> and Barbour, <NAME>},
pages = {268-276},
url = {http://dx.doi.org/10.1002/cyto.a.22444},
year = {2014},
month = {mar},
urldate = {2018-10-23},
journal = {Cytometry A},
volume = {85},
number = {3},
doi = {10.1002/cyto.a.22444},
pmid = {24464647},
abstract = {Methods to detect intracellular kinase signaling intermediates by flow cytometry have been recently developed. Termed "phospho-flow," these methods employ fluorescence-conjugated monoclonal antibodies that recognize phosphorylated epitopes of intracellular kinases, and may be combined with surface phenotypic markers to observe changes in kinase pathways by cellular subset. Effector functions, like cytokine production, are processes intrinsically linked to intracellular signaling and kinase activity within each cell. Methodologies that would simultaneously detect changes to signaling pathways as well as effector responses at the single-cell level would allow for mapping of the functional consequences induced by signaling pathway modifications. However, there are challenges to developing such a combined protocol, relating to the different kinetics of rapid signaling events and the more prolonged time required to induce and observe cytokine responses. In this report, we describe the development of an assay that accommodates differences in protocol conditions and response kinetics, merging phospho-flow cytometry, and intracellular cytokine staining methods into a single experimental protocol. We examined intracellular {ERK1}/2 phosphorylation and {IFN}-\gamma production by {CD4}+ and {CD8}+ T cells upon polyclonal stimulation with {PMA} and ionomycin, while monitoring expression of the cytolytic molecule perforin and the T cell activation marker {CD38}. We present a method that allows observation of kinase phosphorylation and cytokine production within the same cell after stimuli, while maintaining a stable cellular phenotype. Monitoring of signaling and effector functions in distinct immune subsets provides a platform to investigate and relate intracellular kinase signaling activity to immune cell effector function and phenotype in disease states.\copyright 2014 International Society for Advancement of Cytometry.}
}
@article{wolpert_1997,
title = {No free lunch theorems for optimization},
author = {<NAME> <NAME>.},
pages = {67-82},
url = {http://ieeexplore.ieee.org/lpdocs/epic03/wrapper.htm?arnumber=585893},
year = {1997},
month = {apr},
urldate = {2018-08-15},
journal = {{IEEE} Trans. Evol. Computat.},
volume = {1},
number = {1},
issn = {1089778X},
doi = {10.1109/4235.585893},
f1000-projects = {immuEN}
}
@article{eke_2015,
title = {Update on Prevalence of Periodontitis in Adults in the United States: {NHANES} 2009 to 2012.},
author = {<NAME> and Dye, <NAME> and <NAME> and Slade, <NAME> and Thornton-Evans, <NAME> and Borgnakke, <NAME> and Taylor, <NAME>, <NAME> and Genco, <NAME>},
pages = {611-622},
url = {http://dx.doi.org/10.1902/jop.2015.140520},
year = {2015},
month = {may},
urldate = {2018-09-14},
journal = {J Periodontol},
volume = {86},
number = {5},
doi = {10.1902/jop.2015.140520},
pmid = {25688694},
pmcid = {PMC4460825},
f1000-projects = {immuEN},
abstract = {{BACKGROUND}: This report describes prevalence, severity, and extent of periodontitis in the {US} adult population using combined data from the 2009 to 2010 and 2011 to 2012 cycles of the National Health and Nutrition Examination Survey ({NHANES}). {METHODS}: Estimates were derived for dentate adults, aged ≥30 years, from the {US} civilian non-institutionalized population. Periodontitis was defined by combinations of clinical attachment loss ({AL}) and periodontal probing depth ({PD}) from six sites per tooth on all teeth, except third molars, using standard surveillance case definitions. For the first time in {NHANES} history, sufficient numbers of non-Hispanic Asians were sampled in 2011 to 2012 to provide reliable estimates of their periodontitis prevalence. {RESULTS}: In 2009 to 2012, 46\% of {US} adults, representing 64.7 million people, had periodontitis, with 8.9\% having severe periodontitis. Overall, 3.8\% of all periodontal sites (10.6\% of all teeth) had {PD} ≥4 mm, and 19.3\% of sites (37.4\% teeth) had {AL} ≥3 mm. Periodontitis prevalence was positively associated with increasing age and was higher among males. Periodontitis prevalence was highest in Hispanics (63.5\%) and non-Hispanic blacks (59.1\%), followed by non-Hispanic Asian Americans (50.0\%), and lowest in non-Hispanic whites (40.8\%). Prevalence varied two-fold between the lowest and highest levels of socioeconomic status, whether defined by poverty or education. {CONCLUSIONS}: This study confirms a high prevalence of periodontitis in {US} adults aged ≥30 years, with almost fifty-percent affected. The prevalence was greater in non-Hispanic Asians than non-Hispanic whites, although lower than other minorities. The distribution provides valuable information for population-based action to prevent or manage periodontitis in {US} adults.}
}
@article{blencowe_2012,
title = {National, regional, and worldwide estimates of preterm birth rates in the year 2010 with time trends since 1990 for selected countries: a systematic analysis and implications.},
author = {<NAME> and Cousens, <NAME>, <NAME>, Doris and Moller, Ann-Beth and <NAME>, Alma and <NAME>, Claudia and <NAME> and <NAME> and Lawn, <NAME>},
pages = {2162-2172},
url = {http://dx.doi.org/10.1016/S0140-6736(12)60820-4},
year = {2012},
month = {jun},
day = {9},
urldate = {2018-10-17},
journal = {Lancet},
volume = {379},
number = {9832},
doi = {10.1016/S0140-6736(12)60820-4},
pmid = {22682464},
abstract = {{BACKGROUND}: Preterm birth is the second largest direct cause of child deaths in children younger than 5 years. Yet, data regarding preterm birth (\textless 37 completed weeks of gestation) are not routinely collected by {UN} agencies, and no systematic country estimates nor time trend analyses have been done. We report worldwide, regional, and national estimates of preterm birth rates for 184 countries in 2010 with time trends for selected countries, and provide a quantitative assessment of the uncertainty surrounding these estimates. {METHODS}: We assessed various data sources according to prespecified inclusion criteria. National Registries (563 datapoints, 51 countries), Reproductive Health Surveys (13 datapoints, eight countries), and studies identified through systematic searches and unpublished data (162 datapoints, 40 countries) were included. 55 countries submitted additional data during {WHO}'s country consultation process. For 13 countries with adequate quality and quantity of data, we estimated preterm birth rates using country-level loess regression for 2010. For 171 countries, two regional multilevel statistical models were developed to estimate preterm birth rates for 2010. We estimated time trends from 1990 to 2010 for 65 countries with reliable time trend data and more than 10,000 livebirths per year. We calculated uncertainty ranges for all countries. {FINDINGS}: In 2010, an estimated 14·9 million babies (uncertainty range 12·3-18·1 million) were born preterm, 11·1\% of all livebirths worldwide, ranging from about 5\% in several European countries to 18\% in some African countries. More than 60\% of preterm babies were born in south Asia and sub-Saharan Africa, where 52\% of the global livebirths occur. Preterm birth also affects rich countries, for example, {USA} has high rates and is one of the ten countries with the highest numbers of preterm births. Of the 65 countries with estimated time trends, only three (Croatia, Ecuador, and Estonia), had reduced preterm birth rates 1990-2010. {INTERPRETATION}: The burden of preterm birth is substantial and is increasing in those regions with reliable data. Improved recording of all pregnancy outcomes and standard application of preterm definitions is important. We recommend the addition of a data-quality indicator of the per cent of all live preterm births that are under 28 weeks' gestation. Distinguishing preterm births that are spontaneous from those that are provider-initiated is important to monitor trends associated with increased caesarean sections. Rapid scale up of basic interventions could accelerate progress towards Millennium Development Goal 4 for child survival and beyond. {FUNDING}: Bill \& Melinda Gates Foundation through grants to Child Health Epidemiology Reference Group ({CHERG}) and Save the Children's Saving Newborn Lives programme; March of Dimes; the Partnership for Maternal Newborn and Childe Health; and {WHO}, Department of Reproductive Health and Research. Copyright \copyright 2012 Elsevier Ltd. All rights reserved.}
}
@article{liu_2016,
title = {Global, regional, and national causes of under-5 mortality in 2000-15: an updated systematic analysis with implications for the Sustainable Development Goals.},
author = {<NAME> Oza, Shefali and <NAME> and Chu, Yue and Perin, Jamie and <NAME> and Lawn, <NAME> and Cousens, Simon and Mathers, Colin and <NAME>},
pages = {3027-3035},
url = {http://dx.doi.org/10.1016/S0140-6736(16)31593-8},
year = {2016},
month = {dec},
day = {17},
urldate = {2018-10-17},
journal = {Lancet},
volume = {388},
number = {10063},
doi = {10.1016/S0140-6736(16)31593-8},
pmid = {27839855},
pmcid = {PMC5161777},
abstract = {{BACKGROUND}: Despite remarkable progress in the improvement of child survival between 1990 and 2015, the Millennium Development Goal ({MDG}) 4 target of a two-thirds reduction of under-5 mortality rate ({U5MR}) was not achieved globally. In this paper, we updated our annual estimates of child mortality by cause to 2000-15 to reflect on progress toward the {MDG} 4 and consider implications for the Sustainable Development Goals ({SDG}) target for child survival. {METHODS}: We increased the estimation input data for causes of deaths by 43\% among neonates and 23\% among 1-59-month-olds, respectively. We used adequate vital registration ({VR}) data where available, and modelled cause-specific mortality fractions applying multinomial logistic regressions using adequate {VR} for low {U5MR} countries and verbal autopsy data for high {U5MR} countries. We updated the estimation to use Plasmodium falciparum parasite rate in place of malaria index in the modelling of malaria deaths; to use adjusted empirical estimates instead of modelled estimates for China; and to consider the effects of pneumococcal conjugate vaccine and rotavirus vaccine in the estimation. {FINDINGS}: In 2015, among the 5·9 million under-5 deaths, 2·7 million occurred in the neonatal period. The leading under-5 causes were preterm birth complications (1·055 million [95\% uncertainty range ({UR}) 0·935-1·179]), pneumonia (0·921 million [0·812 -1·117]), and intrapartum-related events (0·691 million [0·598 -0·778]). In the two {MDG} regions with the most under-5 deaths, the leading cause was pneumonia in sub-Saharan Africa and preterm birth complications in southern Asia. Reductions in mortality rates for pneumonia, diarrhoea, neonatal intrapartum-related events, malaria, and measles were responsible for 61\% of the total reduction of 35 per 1000 livebirths in {U5MR} in 2000-15. Stratified by {U5MR}, pneumonia was the leading cause in countries with very high {U5MR}. Preterm birth complications and pneumonia were both important in high, medium high, and medium child mortality countries; whereas congenital abnormalities was the most important cause in countries with low and very low {U5MR}. {INTERPRETATION}: In the {SDG} era, countries are advised to prioritise child survival policy and programmes based on their child cause-of-death composition. Continued and enhanced efforts to scale up proven life-saving interventions are needed to achieve the {SDG} child survival target. {FUNDING}: Bill \& Melinda Gates Foundation, {WHO}. Copyright \copyright 2016 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the {CC} {BY} license. Published by Elsevier Ltd.. All rights reserved.}
}
@article{zieglerheitbrock_1993,
title = {{CD14}: cell surface receptor and differentiation marker.},
author = {Ziegler-Heitbrock, <NAME> and Ulevitch, <NAME>},
pages = {121-125},
url = {http://dx.doi.org/10.1016/0167-5699(93)90212-4},
year = {1993},
month = {mar},
urldate = {2018-11-08},
journal = {Immunol Today},
volume = {14},
number = {3},
doi = {10.1016/0167-5699(93)90212-4},
pmid = {7682078},
abstract = {In the past, {CD14} has been viewed simply as a useful marker molecule for monocytes and macrophages. Now, new findings on its role in binding of {LPS}-{LBP} complexes and in signal transduction have engendered renewed interest in the properties of {CD14}. Here, {CD14} function, its expression in different cell types and the regulation of expression, including the generation of soluble {CD14}, are described, and the diagnostic value of {CD14} in various diseases is discussed.}
}
@article{rieckmann_2017,
title = {Social network architecture of human immune cells unveiled by quantitative proteomics.},
author = {Rieckmann, <NAME> and <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, <NAME>, Felix},
pages = {583-593},
url = {http://dx.doi.org/10.1038/ni.3693},
year = {2017},
month = {mar},
day = {6},
urldate = {2018-12-05},
journal = {Nat Immunol},
volume = {18},
number = {5},
doi = {10.1038/ni.3693},
pmid = {28263321},
abstract = {The immune system is unique in its dynamic interplay between numerous cell types. However, a system-wide view of how immune cells communicate to protect against disease has not yet been established. We applied high-resolution mass-spectrometry-based proteomics to characterize 28 primary human hematopoietic cell populations in steady and activated states at a depth of \textgreater10,000 proteins in total. Protein copy numbers revealed a specialization of immune cells for ligand and receptor expression, thereby connecting distinct immune functions. By integrating total and secreted proteomes, we discovered fundamental intercellular communication structures and previously unknown connections between cell types. Our publicly accessible (http://www.immprot.org/) proteomic resource provides a framework for the orchestration of cellular interplay and a reference for altered communication associated with pathology.}
}
@article{davis_2017,
title = {Systems immunology: just getting started.},
author = {<NAME> and Tato, <NAME> and <NAME>},
pages = {725-732},
url = {http://dx.doi.org/10.1038/ni.3768},
year = {2017},
month = {jun},
day = {20},
urldate = {2018-08-17},
journal = {Nat Immunol},
volume = {18},
number = {7},
doi = {10.1038/ni.3768},
pmid = {28632713},
pmcid = {PMC5790187},
f1000-projects = {immuEN},
abstract = {Systems-biology approaches in immunology take various forms, but here we review strategies for measuring a broad swath of immunological functions as a means of discovering previously unknown relationships and phenomena and as a powerful way of understanding the immune system as a whole. This approach has rejuvenated the field of vaccine development and has fostered hope that new ways will be found to combat infectious diseases that have proven refractory to classical approaches. Systems immunology also presents an important new strategy for understanding human immunity directly, taking advantage of the many ways the immune system of humans can be manipulated.}
}
@article{aghaeepour_2017,
title = {An immune clock of human pregnancy.},
author = {<NAME>, <NAME> Mcilwain, <NAME>, <NAME>, <NAME> <NAME>, <NAME>, <NAME>, Quentin and {McNeil}, Leslie and Okada, <NAME>, <NAME> and Furman, <NAME>, <NAME>, <NAME>, <NAME> and El-Sayed, <NAME> and Quaintance, Cecele and Gibbs, Ronald and Darmstadt, <NAME> and Shaw, <NAME> and Stevenson, <NAME> and Tibshirani, Robert and Nolan, <NAME> and Lewis, <NAME> and Angst, <NAME> and Gaudilliere, Brice},
url = {http://dx.doi.org/10.1126/sciimmunol.aan2946},
year = {2017},
month = {sep},
day = {1},
urldate = {2018-08-10},
journal = {Sci Immunol},
volume = {2},
number = {15},
doi = {10.1126/sciimmunol.aan2946},
pmid = {28864494},
pmcid = {PMC5701281},
f1000-projects = {immuEN},
abstract = {The maintenance of pregnancy relies on finely tuned immune adaptations. We demonstrate that these adaptations are precisely timed, reflecting an immune clock of pregnancy in women delivering at term. Using mass cytometry, the abundance and functional responses of all major immune cell subsets were quantified in serial blood samples collected throughout pregnancy. Cell signaling-based Elastic Net, a regularized regression method adapted from the elastic net algorithm, was developed to infer and prospectively validate a predictive model of interrelated immune events that accurately captures the chronology of pregnancy. Model components highlighted existing knowledge and revealed previously unreported biology, including a critical role for the interleukin-2-dependent {STAT5ab} signaling pathway in modulating T cell function during pregnancy. These findings unravel the precise timing of immunological events occurring during a term pregnancy and provide the analytical framework to identify immunological deviations implicated in pregnancy-related pathologies. Copyright \copyright 2017 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 ({CC} {BY}).}
}
@article{jain_2000,
title = {Statistical pattern recognition: a review},
author = {<NAME>. and <NAME>. and <NAME>,},
pages = {4-37},
url = {http://ieeexplore.ieee.org/document/824819/},
year = {2000},
urldate = {2018-12-04},
journal = {{IEEE} Trans Pattern Anal Mach Intell},
volume = {22},
number = {1},
issn = {01628828},
doi = {10.1109/34.824819}
}
@article{bakker_2018,
title = {Integration of multi-omics data and deep phenotyping enables prediction of cytokine responses.},
author = {Bakker, <NAME> and Aguirre-Gamboa, Raul and Sanna, Serena and Oosting, Marije and Smeekens, <NAME> and Jaeger, Martin and Zorro, Maria and Võsa, Urmo and Withoff, Sebo and Netea-Maier, <NAME> and Koenen, <NAME> and Joosten, Irma and <NAME> and Franke, Lude and Joosten, <NAME> and Kumar, Vinod and Wijmenga, Cisca and Netea, <NAME> and <NAME>},
pages = {776-786},
url = {http://www.nature.com/articles/s41590-018-0121-3},
year = {2018},
month = {jul},
urldate = {2018-08-17},
journal = {Nat Immunol},
volume = {19},
number = {7},
issn = {1529-2908},
doi = {10.1038/s41590-018-0121-3},
pmid = {29784908},
pmcid = {PMC6022810},
f1000-projects = {immuEN},
abstract = {The immune response to pathogens varies substantially among people. Whereas both genetic and nongenetic factors contribute to interperson variation, their relative contributions and potential predictive power have remained largely unknown. By systematically correlating host factors in 534 healthy volunteers, including baseline immunological parameters and molecular profiles (genome, metabolome and gut microbiome), with cytokine production after stimulation with 20 pathogens, we identified distinct patterns of co-regulation. Among the 91 different cytokine-stimulus pairs, 11 categories of host factors together explained up to 67\% of interindividual variation in cytokine production induced by stimulation. A computational model based on genetic data predicted the genetic component of stimulus-induced cytokine production (correlation 0.28-0.89), and nongenetic factors influenced cytokine production as well.}
}
@article{ghaemi_2019,
title = {Multiomics modeling of the immunome, transcriptome, microbiome, proteome and metabolome adaptations during human pregnancy.},
author = {Ghaemi, <NAME> and {DiGiulio}, <NAME> and Contrepois, Kévin and Callahan, Benjamin and Ngo, <NAME> and Lee-{McMullen}, Brittany and Lehallier, Benoit and Robaczewska, Anna and Mcilwain, David and Rosenberg-Hasson, <NAME>, <NAME>, <NAME>, Anthony and Stanley, Natalie and Tanada, Athena and Tsai, Amy and Gaudilliere, Dyani and Ganio, <NAME> and <NAME> and {McNeil}, Leslie and Tingle, Martha and Wise, Paul and Maric, Ivana and Sirota, Marina and Wyss-Coray, Tony and Winn, <NAME> and Druzin, <NAME> and Gibbs, Ronald and Darmstadt, <NAME> and Lewis, <NAME> and <NAME>, Vahid and Agard, Bruno and Tibshirani, Robert and Nolan, Garry and Snyder, <NAME> and Relman, <NAME> and Quake, <NAME> and Shaw, <NAME> and Stevenson, <NAME> and Angst, <NAME> and Gaudilliere, Brice and Aghaeepour, Nima},
pages = {95-103},
url = {https://academic.oup.com/bioinformatics/advance-article/doi/10.1093/bioinformatics/bty537/5047759},
year = {2019},
month = {jan},
day = {1},
urldate = {2019-02-04},
journal = {Bioinformatics},
volume = {35},
number = {1},
issn = {1367-4803},
doi = {10.1093/bioinformatics/bty537},
pmid = {30561547},
pmcid = {PMC6298056},
abstract = {Motivation: Multiple biological clocks govern a healthy pregnancy. These biological mechanisms produce immunologic, metabolomic, proteomic, genomic and microbiomic adaptations during the course of pregnancy. Modeling the chronology of these adaptations during full-term pregnancy provides the frameworks for future studies examining deviations implicated in pregnancy-related pathologies including preterm birth and preeclampsia. Results: We performed a multiomics analysis of 51 samples from 17 pregnant women, delivering at term. The datasets included measurements from the immunome, transcriptome, microbiome, proteome and metabolome of samples obtained simultaneously from the same patients. Multivariate predictive modeling using the Elastic Net ({EN}) algorithm was used to measure the ability of each dataset to predict gestational age. Using stacked generalization, these datasets were combined into a single model. This model not only significantly increased predictive power by combining all datasets, but also revealed novel interactions between different biological modalities. Future work includes expansion of the cohort to preterm-enriched populations and in vivo analysis of immune-modulating interventions based on the mechanisms identified. Availability and implementation: Datasets and scripts for reproduction of results are available through: https://nalab.stanford.edu/multiomics-pregnancy/. Supplementary information: Supplementary data are available at Bioinformatics online.}
}
@article{kveler_2018,
title = {Immune-centric network of cytokines and cells in disease context identified by computational mining of {PubMed}.},
author = {<NAME> <NAME> Ziv-Kenet, <NAME>, <NAME>, Yuri and Shalev-Malul, Gali and Aizenbud-Reshef, Netta and Dubovik, Tania and Briller, Mayan and Campbell, John and Rieckmann, <NAME> and Asbeh, Nuaman and Rimar, Doron and Meissner, Felix and Wiser, Jeff and Shen-Orr, <NAME>},
pages = {651-659},
url = {http://www.nature.com/doifinder/10.1038/nbt.4152},
year = {2018},
month = {jun},
day = {18},
urldate = {2019-01-10},
journal = {Nat Biotechnol},
volume = {36},
number = {7},
issn = {1087-0156},
doi = {10.1038/nbt.4152},
pmid = {29912209},
pmcid = {PMC6035104},
abstract = {Cytokines are signaling molecules secreted and sensed by immune and other cell types, enabling dynamic intercellular communication. Although a vast amount of data on these interactions exists, this information is not compiled, integrated or easily searchable. Here we report {immuneXpresso}, a text-mining engine that structures and standardizes knowledge of immune intercellular communication. We applied {immuneXpresso} to {PubMed} to identify relationships between 340 cell types and 140 cytokines across thousands of diseases. The method is able to distinguish between incoming and outgoing interactions, and it includes the effect of the interaction and the cellular function involved. These factors are assigned a confidence score and linked to the disease. By leveraging the breadth of this network, we predicted and experimentally verified previously unappreciated cell-cytokine interactions. We also built a global immune-centric view of diseases and used it to predict cytokine-disease associations. This standardized knowledgebase (http://www.immunexpresso.org) opens up new directions for interpretation of immune data and model-driven systems immunology.}
}
@article{tibshirani_1996,
title = {Regression Shrinkage and Selection via the Lasso},
author = {<NAME>},
pages = {267-288},
publisher = {Wiley for the Royal Statistical Society},
url = {https://www.jstor.org/stable/2346178},
year = {1996},
urldate = {2018-08-10},
journal = {Journal of the Royal Statistical Society. Series B (Methodological)},
volume = {58},
number = {1},
f1000-projects = {immuEN}
}
@article{zou_2005,
title = {Regularization and variable selection via the elastic net},
author = {<NAME> and <NAME>},
publisher = {Wiley/Blackwell (10.1111)},
url = {https://rss.onlinelibrary.wiley.com/doi/abs/10.1111/j.1467-9868.2005.00503.x\%4010.1111/\%{28I\SSN\}%291467-9868.{TOP\_SERIES\_B\_RESEARCH}},
year = {2005},
month = {apr},
day = {1},
urldate = {2018-08-10},
journal = {Journal of the Royal Statistical Society: Series B (Statistical Methodology)},
f1000-projects = {immuEN}
}
@article{maaten_2008,
title = {Visualizing Data using t-{SNE}},
author = {Maaten, <NAME> and Hinton, Geoffrey},
url = {http://www.jmlr.org/papers/v9/vandermaaten08a.html},
year = {2008},
urldate = {2018-08-16},
journal = {Journal of Machine Learning Research}
}
@article{hoerl_1970,
title = {Ridge regression: biased estimation for nonorthogonal problems},
author = {Hoerl, <NAME>. and <NAME>.},
pages = {55},
url = {https://www.jstor.org/stable/1267351?origin=crossref},
year = {1970},
month = {feb},
urldate = {2018-09-27},
journal = {Technometrics},
volume = {12},
number = {1},
issn = {00401706},
doi = {10.2307/1267351}
}
@article{kellywelch_2005,
title = {Interleukin-4 ({IL}-4) pathway.},
author = {<NAME> <NAME> <NAME>},
pages = {cm9},
url = {http://dx.doi.org/10.1126/stke.2932005cm9},
year = {2005},
month = {jul},
day = {19},
urldate = {2018-10-23},
journal = {Sci {STKE}},
volume = {2005},
number = {293},
doi = {10.1126/stke.2932005cm9},
pmid = {16030287},
abstract = {Interleukin-4 ({IL}-4) is a cytokine produced by T(H)2 type helper T cells and by mast cells, basophils, and eosinophils. This cytokine can elicit many responses, some of which are associated with allergy and asthma. Studies with long-term cell lines and primary cells have revealed differences in the signaling between these two experimental systems. Understanding these differences is important because therapeutic strategies targeting {IL}-4 and its signaling pathways are currently being tested to treat allergy and asthma.}
}
@article{cui_2014,
title = {{TLR4} ligands lipopolysaccharide and monophosphoryl lipid a differentially regulate effector and memory {CD8}+ T Cell differentiation.},
author = {<NAME> and <NAME> and <NAME> and <NAME> and <NAME> and <NAME>},
pages = {4221-4232},
url = {http://dx.doi.org/10.4049/jimmunol.1302569},
year = {2014},
month = {may},
day = {1},
urldate = {2018-10-23},
journal = {J Immunol},
volume = {192},
number = {9},
doi = {10.4049/jimmunol.1302569},
pmid = {24659688},
pmcid = {PMC4071140},
abstract = {Vaccines formulated with nonreplicating pathogens require adjuvants to help bolster immunogenicity. The role of adjuvants in Ab production has been well studied, but how they influence memory {CD8}(+) T cell differentiation remains poorly defined. In this study we implemented dendritic cell-mediated immunization to study the effects of commonly used adjuvants, {TLR} ligands, on effector and memory {CD8}(+) T cell differentiation in mice. Intriguingly, we found that the {TLR4} ligand {LPS} was far more superior to other {TLR} ligands in generating memory {CD8}(+) T cells upon immunization. {LPS} boosted clonal expansion similar to the other adjuvants, but fewer of the activated {CD8}(+) T cells died during contraction, generating a larger pool of memory cells. Surprisingly, monophosphoryl lipid A ({MPLA}), another {TLR4} ligand, enhanced clonal expansion of effector {CD8}(+) T cells, but it also promoted their terminal differentiation and contraction; thus, fewer memory {CD8}(+) T cells formed, and {MPLA}-primed animals were less protected against secondary infection compared with those primed with {LPS}. Furthermore, gene expression profiling revealed that {LPS}-primed effector cells displayed a stronger pro-memory gene expression signature, whereas the gene expression profile of {MPLA}-primed effector cells aligned closer with terminal effector {CD8}(+) T cells. Lastly, we demonstrated that the {LPS}-{TLR4}-derived "pro-memory" signals were {MyD88}, but not Toll/{IL}-{1R} domain-containing adapter inducing {IFN}-\beta, dependent. This study reveals the influential power of adjuvants on the quantity and quality of {CD8}(+) T cell memory, and that attention to adjuvant selection is crucial because boosting effector cell expansion may not always equate with more memory T cells or greater protection.}
}
@article{ryu_2018,
title = {Fibrin-targeting immunotherapy protects against neuroinflammation and neurodegeneration.},
author = {<NAME> Rafalski, <NAME> and Meyer-Franke, <NAME>, <NAME> and Poda, <NAME> and <NAME>, <NAME> and Pedersen, <NAME> and <NAME> and Baeten, <NAME> and Sikorski, <NAME> and Bedard, Catherine and Hanspers, Kristina and Bardehle, Sophia and Mendiola, <NAME> and Davalos, Dimitrios and Machado, <NAME> and Chan, <NAME> and Plastira, Ioanna and Petersen, <NAME> and Pfaff, <NAME> and Ang, <NAME> and Hallenbeck, <NAME> and Syme, Catriona and Hakozaki, Hiroyuki and Ellisman, <NAME> and Swanson, <NAME> and Zamvil, <NAME> and Arkin, <NAME> and Zorn, <NAME> and Pico, <NAME> and Mucke, <NAME>, <NAME> and Stavenhagen, <NAME> and Nelson, <NAME> and Akassoglou, Katerina},
pages = {1212-1223},
url = {http://www.nature.com/articles/s41590-018-0232-x},
year = {2018},
month = {nov},
urldate = {2019-02-05},
journal = {Nat Immunol},
volume = {19},
number = {11},
issn = {1529-2908},
doi = {10.1038/s41590-018-0232-x},
pmid = {30323343},
pmcid = {PMC6317891},
abstract = {Activation of innate immunity and deposition of blood-derived fibrin in the central nervous system ({CNS}) occur in autoimmune and neurodegenerative diseases, including multiple sclerosis ({MS}) and Alzheimer's disease ({AD}). However, the mechanisms that link disruption of the blood-brain barrier ({BBB}) to neurodegeneration are poorly understood, and exploration of fibrin as a therapeutic target has been limited by its beneficial clotting functions. Here we report the generation of monoclonal antibody {5B8}, targeted against the cryptic fibrin epitope \gamma377-395, to selectively inhibit fibrin-induced inflammation and oxidative stress without interfering with clotting. {5B8} suppressed fibrin-induced nicotinamide adenine dinucleotide phosphate ({NADPH}) oxidase activation and the expression of proinflammatory genes. In animal models of {MS} and {AD}, {5B8} entered the {CNS} and bound to parenchymal fibrin, and its therapeutic administration reduced the activation of innate immunity and neurodegeneration. Thus, fibrin-targeting immunotherapy inhibited autoimmunity- and amyloid-driven neurotoxicity and might have clinical benefit without globally suppressing innate immunity or interfering with coagulation in diverse neurological diseases.}
}
@article{nettey_2018,
title = {{OMIP}-050: A 28-color/30-parameter Fluorescence Flow Cytometry Panel to Enumerate and Characterize Cells Expressing a Wide Array of Immune Checkpoint Molecules.},
author = {Nettey, <NAME> Giles, <NAME> and Chattopadhyay, <NAME>},
pages = {1094-1096},
url = {http://dx.doi.org/10.1002/cyto.a.23608},
year = {2018},
month = {nov},
urldate = {2018-11-07},
journal = {Cytometry A},
volume = {93},
number = {11},
doi = {10.1002/cyto.a.23608},
pmid = {30347136}
}
@article{saphire_2018,
title = {Antibody-mediated protection against Ebola virus.},
author = {Saphire, <NAME> Schendel, <NAME> and Gunn, <NAME> and Milligan, <NAME> and Alter, Galit},
pages = {1169-1178},
url = {http://dx.doi.org/10.1038/s41590-018-0233-9},
year = {2018},
month = {nov},
urldate = {2019-02-05},
journal = {Nat Immunol},
volume = {19},
number = {11},
doi = {10.1038/s41590-018-0233-9},
pmid = {30333617},
abstract = {Recent Ebola virus disease epidemics have highlighted the need for effective vaccines and therapeutics to prevent future outbreaks. Antibodies are clearly critical for control of this deadly disease; however, the specific mechanisms of action of protective antibodies have yet to be defined. In this Perspective we discuss the antibody features that correlate with in vivo protection during infection with Ebola virus, based on the results of a systematic and comprehensive study of antibodies directed against this virus. Although neutralization activity mediated by the Fab domains of the antibody is strongly correlated with protection, recruitment of immune effector functions by the Fc domain has also emerged as a complementary, and sometimes alternative, route to protection. For a subset of antibodies, Fc-mediated clearance and killing of infected cells seems to be the main driver of protection after exposure and mirrors observations in vaccination studies. Continued analysis of antibodies that achieve protection partially or wholly through Fc-mediated functions, the precise functions required, the intersection with specificity and the importance of these functions in different animal models is needed to identify and begin to capitalize on Fc-mediated protection in vaccines and therapeutics alike.}
}
@book{hastie_2016,
title = {The Elements of Statistical Learning: Data Mining, Inference, and Prediction, Second Edition (Springer Series in Statistics)},
author = {<NAME> and Tibshirani, Robert and <NAME>},
publisher = {Springer},
url = {https://www.amazon.com/Elements-Statistical-Learning-Prediction-Statistics/dp/0387848576},
year = {2016},
urldate = {2018-12-04},
edition = {2nd},
isbn = {9780387848570}
}
@article{zhou_2008,
title = {Angiotensin receptor agonistic autoantibodies induce pre-eclampsia in pregnant mice.},
author = {<NAME> and <NAME> <NAME>, <NAME>, <NAME> and Kellems, <NAME> and <NAME>},
pages = {855-862},
url = {http://dx.doi.org/10.1038/nm.1856},
year = {2008},
month = {aug},
urldate = {2018-12-05},
journal = {Nat Med},
volume = {14},
number = {8},
issn = {1546-{170X}},
doi = {10.1038/nm.1856},
pmid = {18660815},
pmcid = {PMC3267158},
abstract = {Pre-eclampsia affects approximately 5\% of pregnancies and remains a leading cause of maternal and neonatal mortality and morbidity in the United States and the world. The clinical hallmarks of this maternal disorder include hypertension, proteinuria, endothelial dysfunction and placental defects. Advanced-stage clinical symptoms include cerebral hemorrhage, renal failure and the {HELLP} (hemolysis, elevated liver enzymes and low platelets) syndrome. An effective treatment of pre-eclampsia is unavailable owing to the poor understanding of the pathogenesis of the disease. Numerous recent studies have shown that women with pre-eclampsia possess autoantibodies, termed {AT}(1)-{AAs}, that bind and activate the angiotensin {II} receptor type 1a ({AT}(1) receptor). We show here that key features of pre-eclampsia, including hypertension, proteinuria, glomerular endotheliosis (a classical renal lesion of pre-eclampsia), placental abnormalities and small fetus size appeared in pregnant mice after injection with either total {IgG} or affinity-purified {AT}(1)-{AAs} from women with pre-eclampsia. These features were prevented by co-injection with losartan, an {AT}(1) receptor antagonist, or by an antibody neutralizing seven-amino-acid epitope peptide. Thus, our studies indicate that pre-eclampsia may be a pregnancy-induced autoimmune disease in which key features of the disease result from autoantibody-induced angiotensin receptor activation. This hypothesis has obvious implications regarding pre-eclampsia screening, diagnosis and therapy.}
}
@article{jensen_2012,
title = {{CD19}+{CD5}+ cells as indicators of preeclampsia.},
author = {<NAME> <NAME>},
pages = {861-868},
url = {http://dx.doi.org/10.1161/{HYPERTENSIONAHA}.111.188276},
year = {2012},
month = {apr},
urldate = {2018-12-05},
journal = {Hypertension},
volume = {59},
number = {4},
doi = {10.1161/{HYPERTENSIONAHA}.111.188276},
pmid = {22353610},
abstract = {Preeclampsia is a devastating pregnancy-associated disorder affecting 5\% to 8\% of pregnant women worldwide. It emerges as an autoimmune-driven disease, and, among others, the autoantibodies against angiotensin type 1 receptor {II} have been proposed to account for preeclampsia symptoms. Despite much attention focused on describing autoantibodies associated with preeclampsia, there is no clue concerning the cell population producing them. {CD19}(+){CD5}(+) B-1a B cells constitute the main source of natural and polyreactive antibodies, which can be directed against own structures. Here, we aimed to identify the B-cell subpopulation responsible for autoantibody production during preeclampsia and to study their regulation, as well as their possible use as markers for the disease. The frequency of {CD19}(+){CD5}(+) cells in peripheral blood of preeclamptic patients is dramatically increased compared with normal pregnant women as analyzed by flow cytometry. This seems to be driven by the high human chorionic gonadotropin levels present in the serum and placenta supernatant of preeclamptic patients versus normal pregnant women. Not only ≈95\% of {CD19}(+){CD5}(+) cells express the human chorionic gonadotropin receptor, but these cells also expand on human chorionic gonadotropin stimulation in a lymphocyte culture. Most importantly, isolated {CD19}(+){CD5}(+) cells produce autoantibodies against angiotensin type 1 receptor {II}, and {CD19}(+){CD5}(+) cells were further detected in the placenta of preeclamptic but not of normal pregnancies where barely B cells are present. Our results identify a B-cell population able to produce pregnancy-pathological autoantibodies as possible markers for preeclampsia, which opens vast diagnostic and therapeutic applications.}
}
@article{matthiesen_2005,
title = {Immunology of preeclampsia.},
author = {<NAME>, <NAME> Ernerudh, <NAME>, <NAME> Jonsson, <NAME>},
pages = {49-61},
url = {http://dx.doi.org/10.1159/000087912},
year = {2005},
urldate = {2018-12-05},
journal = {Chem Immunol Allergy},
volume = {89},
doi = {10.1159/000087912},
pmid = {16129952},
abstract = {Preeclampsia is a placenta-dependent disorder with both local and systemic anomalies with neonatal and maternal morbidity. It is manifested late in pregnancy, but the onset is during early stages of gestation. The current hypothesis regarding the aetiology of preeclampsia is focused on maladaptation of immune responses and defective trophoblast invasion. Thus, an excessive maternal inflammatory response, perhaps directed against foreign fetal antigens, results in a chain of events including shallow trophoblast invasion, defective spiral artery remodelling, placental infarction and release of pro-inflammatory cytokines and placental fragments in the systemic circulation. During normal pregnancy, trophoblasts interact in the decidua with the unique uterine {NK} cells, modifying their cytokine repertoire, regulating adhesion molecules and matrix metalloproteinases. The inability of trophoblasts to accomplish these changes might be a critical factor for the onset of preeclampsia. Several cytokines, produced at the maternal-fetal interface, have an impact on trophoblast invasion. It is suggested that deficiency of interleukin-10 may contribute to enhanced inflammatory responses towards the trophoblasts elicited by e.g. tumour necrosis factor-alpha and interferon-gamma. Consequently, trophoblasts subjected to a high rate of apoptosis are hampered in their invasive capacity resulting in defective transformation of spiral arteries, hypoxia, thrombosis and infarction of the placenta. The ensuing infarction of placenta leads to leakage of increasing amounts of placental fragments and cytokines in the maternal circulation and an exaggerated systemic endothelial activation as identified in preeclampsia. So far, treatment of preeclampsia is focused on signs like hypertension, whereas attempts of modifying immune responses may be a possibility in the future.}
}
@article{deshmukh_2018,
title = {Immunological basis for recurrent fetal loss and pregnancy complications.},
author = {<NAME> <NAME>},
url = {http://dx.doi.org/10.1146/annurev-pathmechdis-012418-012743},
year = {2018},
month = {sep},
day = {5},
urldate = {2018-12-10},
journal = {Annu Rev Pathol},
volume = {14},
number = {1},
doi = {10.1146/annurev-pathmechdis-012418-012743},
pmid = {30183507},
abstract = {Pregnancy stimulates an elaborate assortment of dynamic changes, allowing intimate approximation of genetically discordant maternal and fetal tissues. Although the cellular and molecular details about how this works remain largely undefined, important clues arise from evaluating how a prior pregnancy influences the outcome of a future pregnancy. The risk of complications is consistently increased when complications occurred in a prior pregnancy. Reciprocally, a prior successful pregnancy protects against complications in a future pregnancy. Here, we summarize immunological perturbations associated with fetal loss, with particular focus on how both harmful and protective adaptations may persist in mothers. Immunological aberrancy as a root cause of pregnancy complications is also considered, given their shared overlapping risk factors and the sustained requirement for averting maternal-fetal conflict throughout pregnancy. Understanding pregnancy-induced immunological changes may expose not only new therapeutic strategies for improving pregnancy outcomes but also new facets of how immune tolerance works, and these may be applicable to other physiological and pathological contexts. Expected final online publication date for the Annual Review of Pathology: Mechanisms of Disease Volume 14 is January 24, 2019. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.}
}
@article{lux_2018,
title = {{flowLearn}: fast and precise identification and quality checking of cell populations in flow cytometry.},
author = {Lux, <NAME>, <NAME> and Chauve, <NAME>, <NAME>, <NAME>, <NAME>, Barbara},
pages = {2245-2253},
url = {http://dx.doi.org/10.1093/bioinformatics/bty082},
year = {2018},
month = {jul},
day = {1},
urldate = {2019-01-11},
journal = {Bioinformatics},
volume = {34},
number = {13},
doi = {10.1093/bioinformatics/bty082},
pmid = {29462241},
pmcid = {PMC6022609},
abstract = {Motivation: Identification of cell populations in flow cytometry is a critical part of the analysis and lays the groundwork for many applications and research discovery. The current paradigm of manual analysis is time consuming and subjective. A common goal of users is to replace manual analysis with automated methods that replicate their results. Supervised tools provide the best performance in such a use case, however they require fine parameterization to obtain the best results. Hence, there is a strong need for methods that are fast to setup, accurate and interpretable. Results: {flowLearn} is a semi-supervised approach for the quality-checked identification of cell populations. Using a very small number of manually gated samples, through density alignments it is able to predict gates on other samples with high accuracy and speed. On two state-of-the-art datasets, our tool achieves median(F1)-measures exceeding 0.99 for 31\%, and 0.90 for 80\% of all analyzed populations. Furthermore, users can directly interpret and adjust automated gates on new sample files to iteratively improve the initial training. Availability and implementation: {FlowLearn} is available as an R package on https://github.com/mlux86/{flowLearn}. Evaluation data is publicly available online. Details can be found in the Supplementary Material. Supplementary information: Supplementary data are available at Bioinformatics online.}
}
@article{bergersen_2011,
title = {Weighted lasso with data integration.},
author = {Bergersen, <NAME> <NAME> <NAME>},
url = {http://dx.doi.org/10.2202/1544-6115.1703},
year = {2011},
month = {aug},
day = {29},
urldate = {2019-01-16},
journal = {Stat Appl Genet Mol Biol},
volume = {10},
number = {1},
doi = {10.2202/1544-6115.1703},
pmid = {23089821},
abstract = {The lasso is one of the most commonly used methods for high-dimensional regression, but can be unstable and lacks satisfactory asymptotic properties for variable selection. We propose to use weighted lasso with integrated relevant external information on the covariates to guide the selection towards more stable results. Weighting the penalties with external information gives each regression coefficient a covariate specific amount of penalization and can improve upon standard methods that do not use such information by borrowing knowledge from the external material. The method is applied to two cancer data sets, with gene expressions as covariates. We find interesting gene signatures, which we are able to validate. We discuss various ideas on how the weights should be defined and illustrate how different types of investigations can utilize our method exploiting different sources of external data. Through simulations, we show that our method outperforms the lasso and the adaptive lasso when the external information is from relevant to partly relevant, in terms of both variable selection and prediction.}
}
@article{mollaysa_2017,
title = {Regularising Non-linear Models Using Feature Side-information},
author = {<NAME> <NAME> Kalousis, Alexandros},
url = {https://arxiv.org/abs/1703.02570},
year = {2017},
month = {mar},
day = {7},
urldate = {2019-01-16},
journal = {arXiv},
abstract = {Very often features come with their own vectorial descriptions which provide detailed information about their properties. We refer to these vectorial descriptions as feature side-information. In the standard learning scenario, input is represented as a vector of features and the feature side-information is most often ignored or used only for feature selection prior to model fitting. We believe that feature side-information which carries information about features intrinsic property will help improve model prediction if used in a proper way during learning process. In this paper, we propose a framework that allows for the incorporation of the feature side-information during the learning of very general model families to improve the prediction performance. We control the structures of the learned models so that they reflect features similarities as these are defined on the basis of the side-information. We perform experiments on a number of benchmark datasets which show significant predictive performance gains, over a number of baselines, as a result of the exploitation of the side-information.}
}
@article{hans_2011,
title = {Elastic net regression modeling with the orthant normal prior},
author = {<NAME>},
pages = {1383-1393},
url = {http://www.tandfonline.com/doi/abs/10.1198/jasa.2011.tm09241},
year = {2011},
month = {dec},
urldate = {2019-01-17},
journal = {J Am Stat Assoc},
volume = {106},
number = {496},
issn = {0162-1459},
doi = {10.1198/jasa.2011.tm09241},
abstract = {The elastic net procedure is a form of regularized optimization for linear regression that provides a bridge between ridge regression and the lasso. The estimate that it produces can be viewed as a Bayesian posterior mode under a prior distribution implied by the form of the elastic net penalty. This article broadens the scope of the Bayesian connection by providing a complete characterization of a class of prior distributions that generate the elastic net estimate as the posterior mode. The resulting model-based framework allows for methodology that moves beyond exclusive use of the posterior mode by considering inference based on the full posterior distribution. Two characterizations of the class of prior distributions are introduced: a properly normalized, direct characterization, which is shown to be conjugate for linear regression models, and an alternate representation as a scale mixture of normal distributions. Prior distributions are proposed for the regularization parameters, resulting in an infinite mixture of elastic net regression models that allows for adaptive, data-based shrinkage of the regression coefficients. Posterior inference is easily achieved using Markov chain Monte Carlo ({MCMC}) methods. Uncertainty about model specification is addressed from a Bayesian perspective by assigning prior probabilities to all possible models. Corresponding computational approaches are described. Software for implementing the {MCMC} methods described in this article, written in C++ with an R package interface, is available at http://www.stat.osu.edu/\~hans/software/.}
}
