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tag:blogger.com,1999:blog-104430502014-10-14T03:38:23.111-04:00Epistasis BlogFrom the Computational Genetics Laboratory at Dartmouth Medical School (www.epistasis.org)Jason H. Moore, Ph.D.http://firstname.lastname@example.com:blogger.com,1999:blog-10443050.post-72646986774747570962014-08-12T07:56:00.000-04:002014-08-12T07:56:23.940-04:00Diverse convergent evidence in the genetic analysis of complex diseaseThe genetic analysis of common human diseases should not rely solely on one piece of evidence (e.g. a p-value derived from a univariate test). In this paper, we explore integrating multiple sources of evidence in the search for valid genetic associations.

Ciesielski TH, Pendergrass SA, White MJ, Kodaman N, Sobota RS, Huang M, Bartlett J, Li J, Pan Q, Gui J, Selleck SB, Amos CI, Ritchie MD, Moore JH, Williams SM. Diverse convergent evidence in the genetic analysis of complex disease: coordinating omic, informatic, and experimental evidence to better identify and validate risk factors. BioData Min. 2014 Jun 30;7:10. [PDF]

Abstract

In omic research, such as genome wide association studies, researchers seek to repeat their results in other datasets to reduce false positive findings and thus provide evidence for the existence of true associations. Unfortunately this standard validation approach cannot completely eliminate false positive conclusions, and it can also mask many true associations that might otherwise advance our understanding of pathology. These issues beg the question: How can we increase the amount of knowledge gained from high throughput genetic data? To address this challenge, we present an approach that complements standard statistical validation methods by drawing attention to both potential false negative and false positive conclusions, as well as providing broad information for directing future research. The Diverse Convergent Evidence approach (DiCE) we propose integrates information from multiple sources (omics, informatics, and laboratory experiments) to estimate the strength of the available corroborating evidence supporting a given association. This process is designed to yield an evidence metric that has utility when etiologic heterogeneity, variable risk factor frequencies, and a variety of observational data imperfections might lead to false conclusions. We provide proof of principle examples in which DiCE identified strong evidence for associations that have established biological importance, when standard validation methods alone did not provide support. If used as an adjunct to standard validation methods this approach can leverage multiple distinct data types to improve genetic risk factor discovery/validation, promote effective science communication, and guide future research directions.Jason H. Moore, Ph.D.http://firstname.lastname@example.com:blogger.com,1999:blog-10443050.post-71367018060674600532014-08-07T07:50:00.003-04:002014-08-07T07:50:50.699-04:00A classification and characterization of two-locus, pure, strict, epistatic models for simulation and detectionOur latest open-access paper on developing epistasis models that can be used to simulate data for evaluating machine learning methods.

Urbanowicz RJ, Granizo-Mackenzie AL, Kiralis J, Moore JH. A classification and characterization of two-locus, pure, strict, epistatic models for simulation and detection. BioData Min. 2014 Jun 9;7:8. [PDF]

Abstract

The statistical genetics phenomenon of epistasis is widely acknowledged to confound disease etiology. In order to evaluate strategies for detecting these complex multi-locus disease associations, simulation studies are required. The development of the GAMETES software for the generation of complex genetic models, has provided the means to randomly generate an architecturally diverse population of epistatic models that are both pure and strict, i.e. all n loci, but no fewer, are predictive of phenotype. Previous theoretical work characterizing complex genetic models has yet to examine pure, strict, epistasis which should be the most challenging to detect. This study addresses three goals: (1) Classify and characterize pure, strict, two-locus epistatic models, (2) Investigate the effect of model 'architecture' on detection difficulty, and (3) Explore how adjusting GAMETES constraints influences diversity in the generated models.

In this study we utilized a geometric approach to classify pure, strict, two-locus epistatic models by "shape". In total, 33 unique shape symmetry classes were identified. Using a detection difficulty metric, we found that model shape was consistently a significant predictor of model detection difficulty. Additionally, after categorizing shape classes by the number of edges in their shape projections, we found that this edge number was also significantly predictive of detection difficulty. Analysis of constraints within GAMETES indicated that increasing model population size can expand model class coverage but does little to change the range of observed difficulty metric scores. A variable population prevalence significantly increased the range of observed difficulty metric scores and, for certain constraints, also improved model class coverage.

These analyses further our theoretical understanding of epistatic relationships and uncover guidelines for the effective generation of complex models using GAMETES. Specifically, (1) we have characterized 33 shape classes by edge number, detection difficulty, and observed frequency (2) our results support the claim that model architecture directly influences detection difficulty, and (3) we found that GAMETES will generate a maximally diverse set of models with a variable population prevalence and a larger model population size. However, a model population size as small as 1,000 is likely to be sufficient.

Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-91019031746995433822014-08-04T19:02:00.001-04:002014-08-04T19:04:09.462-04:00Why epistasis is important for tackling complex human disease geneticsMy new epistasis review / comment with Trudy Mackay from NC State. Unfortunately, it is not open access. Email me for a pdf.

Mackay TF, Moore JH. Why epistasis is important for tackling complex human disease genetics. Genome Med. 2014 Jun 9;6(6):42. [PubMed]Jason H. Moore, Ph.D.http://firstname.lastname@example.com:blogger.com,1999:blog-10443050.post-79657402847937194332014-07-31T16:17:00.004-04:002014-07-31T16:19:38.867-04:00First complex, then simpleMy new BioData Mining editorial with Dr. James Malley from NIH on approaching machine learning and data science modeling from a complexity point of view.

Malley, JD, Moore JH. First complex, then simple. BioData Mining 2014;7:13 [PDF]Jason H. Moore, Ph.D.http://firstname.lastname@example.com:blogger.com,1999:blog-10443050.post-54147571965973967492014-07-29T10:09:00.003-04:002014-07-29T10:09:54.482-04:00Innovation is often unnerving: the door into summerMy latest BioData Mining editorial with Dr. James Malley from NIH. We discuss innovation and interestingness within the context of biological data mining.

Malley JD, Moore JH. Innovation is often unnerving: the door into summer. BioData Min. 2014 Jul 17;7:12. [PDF]Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-42583408879996457952014-06-09T08:57:00.000-04:002014-06-09T08:57:08.646-04:00Validated context-dependent associations of coronary heart disease risk with genotype variationAn absolutely fabulous paper from Charlie Sing and Andy Clark on the context-dependent effects of GWAS hits. A must read for anyone that believes, as I do, that the assumption of simplicity of genetic architecture is not realistic for most biological traits in humans. I have included below a paper for the PRIM method they used. Also worth a read.

Lusk CM, Dyson G, Clark AG, Ballantyne CM, Frikke-Schmidt R, Tybjærg-Hansen A, Boerwinkle E, Sing CF. Validated context-dependent associations of coronary heart disease risk with genotype variation in the chromosome 9p21 region: the Atherosclerosis Risk in Communities study. Hum Genet. 2014 Jun 3. [PubMed]

Dyson G, Sing CF. Efficient identification of context dependent subgroups of risk from genome-wide association studies. Stat Appl Genet Mol Biol. 2014 Apr 1;13(2):217-26. [PubMed]

Dyson G, Frikke-Schmidt R, Nordestgaard BG, Tybjaerg-Hansen A, Sing CF. Modifications to the Patient Rule-Induction Method that utilize non-additive combinations of genetic and environmental effects to define partitions that predict ischemic heart disease. Genet Epidemiol. 2009 May;33(4):317-24. [PubMed]Jason H. Moore, Ph.D.http://firstname.lastname@example.com:blogger.com,1999:blog-10443050.post-84814260076286247382014-05-02T10:44:00.004-04:002014-05-02T10:44:37.161-04:00Models in BiologyThis is by far one of the best papers I have read in the past year. Very relevant to our efforts to build mathematical, statistical and computation models of the genotype-phenotype relationship in population-based studies of common diseases. Gunawardena BMC Biology 2014, 12:29 [PDF]

Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-28309543897007973862014-04-27T09:36:00.002-04:002014-04-27T09:39:39.914-04:00Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibilityWe have previously published a statistical epistasis network associated with bladder cancer in a population based study (Hu et al., BMC Bioinformatics). This network was highly non-random and contained many genes that were part of the aryl hydrocarbon receptor pathway. Below is a short paper reporting functional genomics annotation of the network.

Hu T, Pan Q, Andrew AS, Langer JM, Cole MD, Tomlinson CR, Karagas MR, Moore JH. Functional genomics annotation of a statistical epistasis network associated with bladder cancer susceptibility. BioData Min. 2014 Apr 11;7(1):5. [BioData Mining]

Abstract

BACKGROUND: Several different genetic and environmental factors have been identified as independent risk factors for bladder cancer in population-based studies. Recent studies have turned to understanding the role of gene-gene and gene-environment interactions in determining risk. We previously developed the bioinformatics framework of statistical epistasis networks (SEN) to characterize the global structure of interacting genetic factors associated with a particular disease or clinical outcome. By applying SEN to a population-based study of bladder cancer among Caucasians in New Hampshire, we were able to identify a set of connected genetic factors with strong and significant interaction effects on bladder cancer susceptibility.

FINDINGS: To support our statistical findings using networks, in the present study, we performed pathway enrichment analyses on the set of genes identified using SEN, and found that they are associated with the carcinogen benzo[a]pyrene, a component of tobacco smoke. We further carried out an mRNA expression microarray experiment to validate statistical genetic interactions, and to determine if the set of genes identified in the SEN were differentially expressed in a normal bladder cell line and a bladder cancer cell line in the presence or absence of benzo[a]pyrene. Significant nonrandom sets of genes from the SEN were found to be differentially expressed in response to benzo[a]pyrene in both the normal bladder cells and the bladder cancer cells. In addition, the patterns of gene expression were significantly different between these two cell types.

CONCLUSIONS: The enrichment analyses and the gene expression microarray results support the idea that SEN analysis of bladder in population-based studies is able to identify biologically meaningful statistical patterns. These results bring us a step closer to a systems genetic approach to understanding cancer susceptibility that integrates population and laboratory-based studies.

Jason H. Moore, Ph.D.http://firstname.lastname@example.com:blogger.com,1999:blog-10443050.post-5948722979773424132014-04-14T13:50:00.002-04:002014-04-14T13:50:31.589-04:00To replicate or not to replicate? The case of pharmacogenetic studiesStatistical replication has always been the gold standard in genome-wide association studies (GWAS). However, as we have previously pointed out, there are many good reasons why true genetic associations might not replicate (Greene et al. 2009). This 2013 paper explores the issue with respect to pharmacogenetic studies. The mantra of GWAS is now focused on the identification of new drug targets using genetic association results. If this is true, should biological validation matter more than statistical replication?

Aslibekyan S, Claas SA, Arnett DK. To replicate or not to replicate: the case of pharmacogenetic studies: Establishing validity of pharmacogenomic findings: from replication to triangulation. Circ Cardiovasc Genet. 2013 Aug;6(4):409-12 [PubMed]Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-10862090957832790832014-04-13T10:28:00.004-04:002014-04-27T09:40:11.458-04:00Why human disease-associated residues appear as the wild-type in other species: genome-scale structural evidence for the compensation hypothesisXu J, Zhang J. Why human disease-associated residues appear as the wild-type in other species: genome-scale structural evidence for the compensation hypothesis. Mol Biol Evol. 2014 [PubMed]

Abstract

Many human-disease associated amino acid residues (DARs) appear as the wild-type in other species. This phenomenon is commonly explained by the presence of compensatory residues in these other species that alleviate the deleterious effects of the DARs. The general validity of this hypothesis, however, is unclear, because few compensatory residues have been identified. Here we test the compensation hypothesis by assembling and analyzing 1077 DARs located in 177 proteins of known crystal structures. Because destabilizing protein structures is a primary reason why DARs are deleterious, we focus on protein stability in this analysis. We discover that, in species where a DAR represents the wild-type, the destabilizing effect of the DAR is generally lessened by the observed amino acid substitutions in the spatial proximity of the DAR. This and other findings provide genome-scale evidence for the compensation hypothesis and have important implications for understanding epistasis in protein evolution and for using animal models of human diseases.
Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-12379174164262242642014-04-12T11:11:00.001-04:002014-04-27T09:44:06.949-04:00Detection and replication of epistasis influencing transcription in humansThis study demonstrates that replicable epistasis is common at the level of transcription.

Hemani G, Shakhbazov K, Westra HJ, Esko T, Henders AK, McRae AF, Yang J, Gibson G, Martin NG, Metspalu A, Franke L, Montgomery GW, Visscher PM, Powell JE. Detection and replication of epistasis influencing transcription in humans. Nature. 2014 Apr 10;508(7495):249-53. [PubMed]

Abstract

Epistasis is the phenomenon whereby one polymorphism's effect on a trait depends on other polymorphisms present in the genome. The extent to which epistasis influences complex traits and contributes to their variation is a fundamental question in evolution and human genetics. Although often demonstrated in artificial gene manipulation studies in model organisms, and some examples have been reported in other species, few examples exist for epistasis among natural polymorphisms in human traits. Its absence from empirical findings may simply be due to low incidence in the genetic control of complex traits, but an alternative view is that it has previously been too technically challenging to detect owing to statistical and computational issues. Here we show, using advanced computation and a gene expression study design, that many instances of epistasis are found between common single nucleotide polymorphisms (SNPs). In a cohort of 846 individuals with 7,339 gene expression levels measured in peripheral blood, we found 501 significant pairwise interactions between common SNPs influencing the expression of 238 genes (P = 2.91 × 10(-16)). Replication of these interactions in two independent data sets showed both concordance of direction of epistatic effects (P = 5.56 × 10(-31)) and enrichment of interaction P values, with 30 being significant at a conservative threshold of P < 9.98 × 10(-5). Forty-four of the genetic interactions are located within 5 megabases of regions of known physical chromosome interactions (P = 1.8 × 10(-10)). Epistatic networks of three SNPs or more influence the expression levels of 129 genes, whereby one cis-acting SNP is modulated by several trans-acting SNPs. For example, MBNL1 is influenced by an additive effect at rs13069559, which itself is masked by trans-SNPs on 14 different chromosomes, with nearly identical genotype-phenotype maps for each cis-trans interaction. This study presents the first evidence, to our knowledge, for many instances of segregating common polymorphisms interacting to influence human traits.Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-46216454218552552992014-02-14T17:59:00.000-05:002014-02-14T17:59:11.620-05:00Promotion and tenure review at universitiesThere is an interesting thread on promotion and tenure by @phylogenomics on twitter using the hashtag #publishperish14. He is tweeting comments from @lindakateh, the chancellor at UC Davis. All the tweets from the conference have been archived here. Some of the discussion was related to whether everyone should have tenure since very few actually don't get it. I also like the comments about the tenure process reducing creativity and risk-taking. She also discussed the idea of rewarding faculty for other forms of expression including blogs.Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-47682393929966624902014-02-12T19:12:00.003-05:002014-04-27T09:40:43.677-04:00P-values, the 'gold standard' of statistical validity, are not as reliable as many scientists assumeThis piece in Nature about the limitations of p-values is a must read. It is very relevant to genetics, epidemiology and, especially, genome-wide association studies (GWAS) that have put so much emphasis on p-values. We have also written about the limitations of p-values in a short editorial.Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-20958513133853737692014-01-30T11:09:00.005-05:002014-04-27T09:41:15.844-04:00Reconciling clinical importance and statistical significance in GWASGenome-wide association studies (GWAS) have identified many risk-associated SNPs with very small effects. The mantra for identifying more associations is to greatly increase the sample size to be able to detect smaller and smaller effects. This wonderful letter in the European Journal of Human Genetics points out that at some point the effect size goes below the measurement error calling into question the clinical significance of these GWAS hits. If I were funding a big GWAS study I would first want to know whether increasing the sample size is justified given the effects sizes to be detected and the error of the phenotype measures.

 Shriner D, Adeyemo A, Rotimi CN. Reconciling clinical importance and statistical significance. Eur J Hum Genet. 2014 Feb;22(2):158-9. [EJHG]
Jason H. Moore, Ph.D.http://firstname.lastname@example.com:blogger.com,1999:blog-10443050.post-4854229725193615562014-01-25T08:41:00.001-05:002014-01-25T08:41:31.405-05:00My take of the FDA's decision to regulate 23andMeIn 2013 the FDA ordered 23andMe to stop selling it's genetic testing services for health-related purposes. This was a very controversial ruling that generated lots of discussion in the media. A collection of links to media coverage and opinions put together by writer David Dobbs can be found here. My take on the issue can be found in this Dartmouth Medicine Magazine piece.Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-69411205955962971672014-01-11T09:24:00.003-05:002014-01-11T09:26:59.099-05:00Percentile Ranking and Citation Impact of a Large Cohort of NHLBI-Funded Cardiovascular R01 GrantsI just ran across this interesting new study that evaluated the relationship between the score that an NIH R01 grant receives during peer-review and the future impact of the grant as measured by number and quality of publications. The bottom line is that a grant that receives a top score in the 10th percentile does not produce publications with impact above and beyond a grant in the 30th percentile that would not be funded by 2014 criteria.

Danthi N, Wu CO, Shi P, Lauer MS. Percentile Ranking and Citation Impact of a Large Cohort of NHLBI-Funded Cardiovascular R01 Grants. Circ Res. 2014 Jan 9. [PubMed]

Abstract

Rationale: Funding decisions for cardiovascular R01 grant applications at NHLBI largely hinge on percentile rankings. It is not known whether this approach enables the highest impact science.

Objective: To conduct an observational analysis of percentile rankings and bibliometric outcomes for a contemporary set of funded NHLBI cardiovascular R01 grants.

Methods and Results: We identified 1492 investigator-initiated de novo R01 grant applications that were funded between 2001 and 2008, and followed their progress for linked publications and citations to those publications. Our co-primary endpoints were citations received per million dollars of funding, citations obtained within 2-years of publication, and 2-year citations for each grant's maximally cited paper. In 7654 grant-years of funding that generated $3004 million of total NIH awards, the portfolio yielded 16,793 publications that appeared between 2001 and 2012 (median per grant 8, 25th and 75th percentiles 4 and 14, range 0 - 123), which received 2,224,255 citations (median per grant 1048, 25th and 75th percentiles 492 and 1,932, range 0 - 16,295). We found no association between percentile ranking and citation metrics; the absence of association persisted even after accounting for calendar time, grant duration, number of grants acknowledged per paper, number of authors per paper, early investigator status, human versus non-human focus, and institutional funding. An exploratory machine-learning analysis suggested that grants with the very best percentile rankings did yield more maximally cited papers.

Conclusions: In a large cohort of NHLBI-funded cardiovascular grants, we were unable to find a monotonic association between better percentile ranking and higher scientific impact as assessed by citation metrics.Jason H. Moore, Ph.D.http://firstname.lastname@example.com:blogger.com,1999:blog-10443050.post-14167457251025239652013-12-30T11:07:00.001-05:002013-12-30T11:20:37.852-05:00Epistasis Blog Posts from 2013January, 2013

Gene-gene interactions in a pathway-based analysis of genetic susceptibility to bladder cancer

February, 2013

Complex effects of nucleotide variants in a mammalian cis-regulatory element

March, 2013

Four tips for success in graduate school and beyond

Gene-based testing of interactions in association studies of quantitative traits

Alternative definitions of epistasis

Role of genetic heterogeneity and epistasis in bladder cancer susceptibility and outcome: a learning classifier system approach

Multifactor dimensionality reduction reveals a three-locus epistatic interaction associated with susceptibility to pulmonary tuberculosis

ViSEN: Methodology and software for visualization of statistical epistasis networks

Statistical epistasis networks reduce the computational complexity of searching three-locus genetic models

An information-gain approach to detecting three-way epistatic interactions in genetic association studies

April, 2013

Things genes can't do. Shall we have pie or stew?

May, 2013

Probabilistic multifactor causation - what do we mean?

Journal impact factors - updated

A robustness study of parametric and non-parametric tests in model-based multifactor dimensionality reduction for epistasis detection

June, 2013

JAMIA special issue on Translational Bioinformatics

July, 2013

A simple extension of Multifactor Dimensionality Reduction (MDR) for detecting epistasis effects on quantitative traits

August, 2013

The effect of genetic background on genetic interaction networks

September, 2013

Genotype-environment interactions reveal causal pathways that mediate genetic effects on phenotype

October, 2013

Best paper award at Translational Bioinformatics Conference

December, 2013

Big data analysis on autopilot?

Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-90495194102078078282013-12-11T09:17:00.001-05:002013-12-11T09:17:09.293-05:00Big Data Analysis on Autopilot?My latest editorial with Scott Williams on whether big data analysis in genomics and other disciplines has shifted into autopilot with potentially dangerous consequences for the study of human health. This paper is open-access.

Williams SM, Moore JH. Big Data analysis on autopilot? BioData Min. 2013;6(1):22. [PubMed] [PDF]Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-42126862295323476952013-10-13T10:20:00.000-04:002013-12-30T11:22:41.614-05:00Best paper award at Translational Bioinformatics ConferenceQinxin Pan from my lab won one of three best paper awards at the 3rd Annual Translational Bioinformatics Conference (TBC) held in Seoul, South Korea on Oct. 2-4, 2013. Her paper on epistasis analysis is one of six from the conference that were invited for publication in a special issue of the Journal of the American Medical Informatics Association (JAMIA).

Qinxin Pan, Ting Hu, Li Shen, Andrew J. Saykin, Jason H. Moore and the Alzheimer's Disease Neuroimaging Initiative. Topological Analysis of Statistical Epistasis Networks Reveals Pathways Associated with Alzheimer's Disease. JAMIA, in press (2014).

Abstract

Most pathway analysis approaches rely on main effects of genes and do not take gene-gene interactions into account. Gene-gene interactions, i.e., epistasis, are believed to account for a portion of the presumed missing heritability. Moreover, conventional methods treat each pathway independently whereas in reality they cooperate and work together as an intertwined system. In this study, we construct statistical epistasis networks (SEN) underlying Alzheimer's disease (AD) and infer risk-associated pathways from their topological structures. We test for pathways that possess central positions in the SENs and characterize the interactions among pathways. We find that pathway glycosphingolipid biosynthesis ganglio series, which has been hypothesized to be involved in AD pathobiology, holds central positions in the SENs and is actively interacting with a high number of other pathways. Other central pathways include alpha linolenic acid metabolism, sphingolipid metabolism, peroxisome, ether lipid metabolism, primary bile acid biosynthesis etc. In addition to pathways possessing central positions in SENs, we identify a few pathways that are frequently interacting with other pathways. The pathways and pathway interactions identified in our study should be further investigated, especially in the context of epistasis.
 Jason H. Moore, Ph.D.http://firstname.lastname@example.com:blogger.com,1999:blog-10443050.post-63898669645191326852013-09-19T20:28:00.000-04:002013-09-19T20:28:02.210-04:00Genotype-Environment Interactions Reveal Causal Pathways That Mediate Genetic Effects on PhenotypeGreat new paper showing GxE in yeast.

Gagneur J, Stegle O, Zhu C, Jakob P, Tekkedil MM, et al. (2013) Genotype-Environment Interactions Reveal Causal Pathways That Mediate Genetic Effects on Phenotype. PLoS Genet 9(9): e1003803. [PLoS]

Abstract

Unraveling the molecular processes that lead from genotype to phenotype is crucial for the understanding and effective treatment of genetic diseases. Knowledge of the causative genetic defect most often does not enable treatment; therefore, causal intermediates between genotype and phenotype constitute valuable candidates for molecular intervention points that can be therapeutically targeted. Mapping genetic determinants of gene expression levels (also known as expression quantitative trait loci or eQTL studies) is frequently used for this purpose, yet distinguishing causation from correlation remains a significant challenge. Here, we address this challenge using extensive, multi-environment gene expression and fitness profiling of hundreds of genetically diverse yeast strains, in order to identify truly causal intermediate genes that condition fitness in a given environment. Using functional genomics assays, we show that the predictive power of eQTL studies for inferring causal intermediate genes is poor unless performed across multiple environments. Surprisingly, although the effects of genotype on fitness depended strongly on environment, causal intermediates could be most reliably predicted from genetic effects on expression present in all environments. Our results indicate a mechanism explaining this apparent paradox, whereby immediate molecular consequences of genetic variation are shared across environments, and environment-dependent phenotypic effects result from downstream integration of environmental signals. We developed a statistical model to predict causal intermediates that leverages this insight, yielding over 400 transcripts, for the majority of which we experimentally validated their role in conditioning fitness. Our findings have implications for the design and analysis of clinical omics studies aimed at discovering personalized targets for molecular intervention, suggesting that inferring causation in a single cellular context can benefit from molecular profiling in multiple contexts.Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-12798015684749379442013-08-17T11:05:00.002-04:002013-12-30T11:04:26.047-05:00The effect of genetic background on genetic interaction networksAn interesting new paper just published in PLoS Genetics.

Chari S, Dworkin I. The conditional nature of genetic interactions: the consequences of wild-type backgrounds on mutational interactions in a genome-wide modifier screen. PLoS Genet. 2013 Aug;9(8):e1003661 [PubMed] [PLoS]

Abstract
The phenotypic outcome of a mutation cannot be simply mapped onto the underlying DNA variant. Instead, the phenotype is a function of the allele, the genetic background in which it occurs and the environment where the mutational effects are expressed. While the influence of genetic background on the expressivity of individual mutations is recognized, its consequences on the interactions between genes, or the genetic network they form, is largely unknown. The description of genetic networks is essential for much of biology; yet if, and how, the topologies of such networks are influenced by background is unknown. Furthermore, a comprehensive examination of the background dependent nature of genetic interactions may lead to identification of novel modifiers of biological processes. Previous work in Drosophila melanogaster demonstrated that wild-type genetic background influences the effects of an allele of scalloped (sd), with respect to both its principal consequence on wing development and its interactions with a mutation in optomotor blind. In this study we address whether the background dependence of mutational interactions is a general property of genetic systems by performing a genome wide dominant modifier screen of the sd(E3) allele in two wild-type genetic backgrounds using molecularly defined deletions. We demonstrate that ∼74% of all modifiers of the sd(E3) phenotype are background-dependent due in part to differential sensitivity to genetic perturbation. These background dependent interactions include some with qualitative differences in the phenotypic outcome, as well as instances of sign epistasis. This suggests that genetic interactions are often contingent on genetic background, with flexibility in genetic networks due to segregating variation in populations. Such background dependent effects can substantially alter conclusions about how genes influence biological processes, the potential for genetic screens in alternative wild-type backgrounds identifying new loci that contribute to trait expression, and the inferences of the topology of genetic networks. Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-47274495788965981762013-07-05T06:32:00.003-04:002013-07-05T06:32:59.815-04:00A simple extension of Multifactor Dimensionality Reduction (MDR) for detecting epistasis effects on quantitative traitsOur Multifactor Dimensionality Reduction (MDR) method and software was developed for detecting and characterizing epistasis or gene-gene interactions in population-based studies. We present here a simple and computationally-efficient extension of MDR that can be used to detect epistasis effects on quantitative traits. This approach is implemented in version 3.0 of our open-source MDR software package.

Gui J, Moore JH, Williams SM, Andrews P, Hillege HL, van der Harst P, Navis G, Van Gilst WH, Asselbergs FW, Gilbert-Diamond D. A Simple and Computationally Efficient Approach to Multifactor Dimensionality Reduction Analysis of Gene-Gene Interactions for Quantitative Traits. PLoS One. 2013 Jun 21;8(6):e66545. [PubMed] [PLoS One] [PDF]

Abstract

We present an extension of the two-class multifactor dimensionality reduction (MDR) algorithm that enables detection and characterization of epistatic SNP-SNP interactions in the context of a quantitative trait. The proposed Quantitative MDR (QMDR) method handles continuous data by modifying MDR's constructive induction algorithm to use a T-test. QMDR replaces the balanced accuracy metric with a T-test statistic as the score to determine the best interaction model. We used a simulation to identify the empirical distribution of QMDR's testing score. We then applied QMDR to genetic data from the ongoing prospective Prevention of Renal and Vascular End-Stage Disease (PREVEND) study.
Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-38348164137870294302013-06-15T09:08:00.001-04:002013-06-15T09:10:17.252-04:00JAMIA Special Issue on Translational BioinformaticsThe June, 2013 issue of the Journal of the American Medical Informatics Association (JAMIA) contains papers published from the 2012 Translational Bioinformatics Conference (TBC). The list of papers can be found here.

We have the following two papers in the special issue. Both are open access.

Hu T, Chen Y, Kiralis JW, Collins RL, Wejse C, Sirugo G, Williams SM, Moore JH. An information-gain approach to detecting three-way epistatic interactions in genetic association studies. J Am Med Inform Assoc. 2013 Jul 1;20(4):630-6. [PubMed]

Urbanowicz RJ, Andrew AS, Karagas MR, Moore JH. Role of genetic heterogeneity and epistasis in bladder cancer susceptibility and outcome: a learning classifier system approach. J Am Med Inform Assoc. 2013 Jul 1;20(4):603-12. [PubMed]

This paper from Yves Lussier is also highly relevant to the complexity of the genotype-phenotype map.

Lee Y, Li H, Li J, Rebman E, Achour I, Regan KE, Gamazon ER, Chen JL, Yang XH, Cox NJ, Lussier YA. Network models of genome-wide association studies uncover the topological centrality of protein interactions in complex diseases. J Am Med Inform Assoc. 2013 Jul 1;20(4):619-29. [PubMed]

Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-11237002067381424592013-05-24T08:05:00.003-04:002013-05-29T20:05:16.021-04:00Probabilistic multifactor causation - what do we mean?This four-part blog post on genetic causation is well worth the long read. I highly recommend it. It is written by Dr. Anne Buchanan and Ken Weiss from Penn State. It is part of The Mermaid's Tale blog.

Who, me? I don't believe in single-gene causation! (or do I?). Part I. What does it mean?

Who, me? I don't believe in single-gene causation! (or do I?). Part II. Probabilistic causation--what do we mean?

 Who, me? I don't believe in single-gene causation! (or do I?). Part III. Probabilistic multifactor causation--what do we mean?

Who, me? I don't believe in single-gene causation! (or do I?). Part IV. Do we need the probabilistic hypothesis?

Be sure and read their awesome book titled "The Mermaid's Tale"

Jason H. Moore, Ph.D.http://email@example.com:blogger.com,1999:blog-10443050.post-61139115029992804702013-05-17T13:41:00.000-04:002013-12-30T11:01:38.067-05:00Journal Impact Factors - UpdatedI updated my August, 2012 blog post about journal impact factors and their value as a measure of success. This post has been updated with the recent DORA report and several editorials about it.Jason H. Moore, Ph.D.http://firstname.lastname@example.com


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UTHSC Houston interview advice?
- 0Nov 7, '08 by My_brain_hurtsHI everyone!
Just got an interview letter from UTHSC Houston and I'm excited, nervous, grateful, relieved, and terrified all rolled into one. This will be my first grad school interview --ever.
Does anybody have any words of wisdom from past interview experience at UTHSCH? I know breathing always helps, as does not vomiting on the admit committee.
- 0Jan 10, '09 by COtraumarnGet there early. They have a couple of students there you can ask questions. There is a panel of about 10 CRNA's that ask you questions. Actually only about 3 or 4 asked questions and the rest just wrote down stuff. They ask a lot of why you want to come to Houston etc etc. Not a whole lot of clinical questions. Show some enthusiasm. I didn't get accepted and when I asked what I could've done better- he said show more enthusiasm. So in between breathing, not sweating through your shirt or blouse ( IDK if you're male or female), and not vomiting on the faculty- put on a happy, cheerleader face.
Best of luck to you.
- 0Feb 19, '09 by turtle and the hareIf you are only planning for Houston then UT Houston all the way. Word of advice ask the students away from faculty how they like the program. Also speak to recent alumni. You will discover many many hidden secrets. Good Luck
- 0Feb 22, '09 by My_brain_hurtsI ended up not getting accepted to UT houston, but I DID get accepted at BAYLOR!!!! who would have thought? I assumed I'd have had a better change at UT. Oh well :spin:
Baylor was really my first choice, but I had kind of talked myself out of it because I figured I really didn't have a chance of getting in there. I mean, I would have been happy at UT and made the best of it because in the end your a CRNA and that's the whole point, not where you graduated from. I know all schools have good/bad/ugly sides, and different students have differing views of the programs they are in. I'm excited because Baylor isn't a nursing school, so no touchy feely stuff. I had enough of that in BSN. Touchy feely is important to a degree, but I want the hard science of anesthesia. I'm excited my time in school will focus on that.
Sooo, when I'm eyeballs deep in studying y'all remind me how happy I am to be in school again. HA! :typing:
- 0Feb 24, '09 by pspraramcongrats on getting into Baylor. I applied there also but didn't get in. Both UT and Baylor had lots of applicants. I'm glad I got in somewhere to be honest with you. I wonder if I met u waiting for my UT interview. I met a girl that works at methodist, a girl from austin or dallas and a guy from Utah I think. I interviewed on the 22nd of January. Anyways, congratulations. Baylor is a great program. Best of luck to you.
- 0Feb 24, '09 by My_brain_hurtsI might have met you. My interview was at 9:30. I came back to the room and had some fruit and I think there was a guy from Utah there talking with the students? I was the girl with the suit on HA! that reeeeally narrows it down. . .
What day did you interview at Baylor? I was there on Feb. 2. I've probably read where you're going but I don't remember. sorry. Sooo where did you get in? Yeah, honestly, I'm just happy to be in school at all. In the end nobody really cares where you went to school. It's all about learning as much as you can and gettint the most from your education and that is up to the individual students I think. The program gives you opportunity, but it's more important what you do with it as a person, in my opinion.
Good luck to you too! I'll be posting many many MANY questions when school starts I'm sure!
- 0Jun 22, '10 by NAM123Hey guys, I am new at this allnurses forum but it seems to be very helpful..
does any one have any advice for the HESI A2 test? what are the science questions like? when i took TEAS they had mainly Biology.
I heard HESI has clinical/application questions too... is that true?
also those who are already enrolled in UTHSC, how is the program? I heard they are very disorganized.

subset: commoncrawl


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Who wouldn't jump at the chance to move to Paris for work? Amy Thomas was a copywriter in New York City when one day her boss offered her a dream gig writing copy for Louis Vuitton — in the City of Lights. Sold! But unlike other ladies who've flown across the pond, Amy wasn't looking for l'amour or even la mode. This sugar-freak intended to use her time in Paris snarfing sweets all the best patisseries and boulangeries, which she lovingly recaps in her foodie memoir, Paris, My Sweet: A Year In The City Of Light (And Dark Chocolate). If an Air France flight is not in your budget, Paris, My Sweet should satiate any cravings you might have … at least temporarily. [$10.19, Amazon]
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Would you be willing to answer a few brief questions about PlayStation Forums?
It might be too late, but you can ask her "How do you get into the mindset of acting like a 14 year old girl, and are there any negatives/positives to that?"
loakum wrote:
I just want her to shout, "we're going wild", she sounds so adorable when she says that! lol
She sounds adorable when she says anything lol. I love her voice.
Now Troy though, Troy can do one killer Christopher Walken voice. I've told myself that if I ever meet Troy the first thing I'll do is ask him to do that for me.


text:
Jim Cramer's Stop Trading! Buy Reliance
Buy Reliance Steel (RS) off the big deal between U.S. Steel (X) and Lone Star (LSS) deal, Jim Cramer said Thursday on CNBC's "Stop Trading!" segment.
Cramer said Reliance, up 3% Thursday afternoon, is "the cheapest that's left" among the consolidation-crazed steel names. Of the U.S. Steel plan to acquire Lone Star, Cramer said, "What a deal."
Cramer likes GlobalSantaFe (GSF), saying a "monster seller" in the stock is giving investors an opportunity to "take advantage of the weakness" that has the stock down fractionally Thursday. Cramer believes Norway's SeaDrill could end up buying or merging with GlobalSantaFe.
Cramer likes Tata Motors (TTM), the Indian auto play, and is taking a look at Frozen Food Express (FFEX) and RadioShack (RSH) on Bob Olstein's advice.
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Doctors in Residency Fail Tests of Common Courtesy
He adds, "when I'm the attending physician, I walk in on rounds with the whole team, introduce myself and put out my hand to shake the patient's hand, and then make the intern who is going to present the case sit down with the patient in a chair next to the bed. I'm showing them how I think it should be done. And they go, 'You know, that's how Dr. Feldman does it, so I should be doing it that way.'
"We teach this in medical school, but then we don't do a good job following up with that in residency education."
Feldman emphasizes that interns should introduce themselves and engage in all four other behaviors during every patient encounter, even if they have seen the patient before. That's because for any patient hospitalized, the experience "has got to be daunting. They've met several emergency room physicians, the intern that's going to take care of them, the whole Hopkins team that rounds the next morning, possibly a pharmacist, a case manager, social worker, a head floor nurse, senior residents, attendings, and maybe a specialty consultant or surgeon.
"So it shouldn't be a lot for us to take 10 seconds to say who we are. If I introduce myself again and the patient says, 'Of course I know who you are Dr. Feldman,' then I know I've done my job."
Comments are moderated. Please be patient.
Pamela D. Simons, MD, MBA, FACOG (10/31/2013 at 11:03 PM)
Given the time limitations of service pressure, the frequent lack of a place to sit down, especially in patient rooms, and the emphasis on EHR, which slows down documentation and prevents eye contact, none of this is surprising. Most residents went into medicine to care for and "be with" patients, but the system increasingly prevents this. It was hard enough 20 years ago when I was in training. Now, it's near-impossible. The practice of medicine increasingly resembles working the front counter at McDonald's. Every layer of administrative demand forced on clinicians increases the cost of providing care and forces us to work faster and gives us less time to think or "be with" our patients in order to generate the same compensation.
JS (10/30/2013 at 2:51 PM)
Healthcare is a customer service business, like it or not. In the event of a poor outcome, the provider who showed genuine caring and concern throughout his/her relationship with the patient is less likely to face a law suit than the provider with poor bedside manner. Treat me well as a patient, yeah I probably won't advertise that to all of my friends, but treat me rudely or make me feel like my issue is unimportant, then I will tell all my friends.
Robert Modugno MD MBA FACOG (10/29/2013 at 4:03 PM)
We are a rude society. I am not surprised.
- 1 in 5 Eligible Hospitals Penalized for HACs
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Lego Batman 2: DC Super Heroes Answers for Nintendo WiiHome / Nintendo Wii /
Game Questions & Answers (Q&A) service lets you ask questions about video games for game consoles or PC games. So ask your Lego Batman 2: DC Super Heroes question for Nintendo Wii and get answers from real gamers or answer questions and share your insights and experience with the rest of the gaming community.
- Developer: TT Games
- Publisher: Warner Bros. Interactive Entertainment
- Genre: Action Adventure Modern
- Release Date: Jun 19, 2012
- ESRB: Everyone 10+
Question & Answers
How to get to level 4
We've completed level 3 but can't seem to find how to get to level 4. We've been told to look for "ghost" studs to show us the way but can't find them. We've been back to the bat cave and got a vehicle but this just takes us to Gotham City.
Answer from: Kool kid
You turn your compass until it faces the bat simbol then go in that direction until you reach the level
Answer from: HelpBMan2isNuty
I followed the above got in the planetarium/atrium/wtf ever it is... building through glitch by getting close to the door with the colored splooge marks and switching characters and bam your in...can do anything but destroy plants.
Unanswered Questions
From: Guest
Posted on: 12-16-2014
From: MissKnowsItAll
Posted on: 09-05-2014
Lego Batman 2: DC Super Heroes - Minifigures Trailer
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DIY Mother's Day Gifts
Go beyond the bouquet this Mother's Day with these thoughtful gifts for Mom.
Instead of the standard bouquet of flowers or box of scented soaps, give Mom a present that's truly personal. Read on for great gifts you can customize or make yourself.
A Personalized Serving Tray
Treat her to breakfast in bed served on a tray engraved with her family's names, a favorite quote or some other meaningful expression. (Other options: Let kids hand-paint a wooden tray, or have a tray customized with family photos or a special design.) Arrange the tray with fresh flowers, monogrammed linen napkins and yummy menu items like our raspberry chocolate tassies or mini chocolate cinnamon buns.
A Treasure Hunt
Kids will have fun creating a set of clue cards, then hiding them around the house and yard to lead Mom to her present. Each clue can include a trivia question about favorite family traditions, memories, and trips that she has to answer before receiving her next clue. (To keep her delighted, include Ghirardelli SQUARES to savor with each clue.) As for the reward at the end of the hunt, Ghirardelli's Sweet Escape Basket, featuring a mouth-watering assortment of chocolate, makes the perfect treasure.
Mom: The Movie
Make a tribute video about Mom. Include interviews with her children (and other relatives and friends) telling what they adore best about her and sharing favorite stories. Add in footage of memorable family events and create a soundtrack featuring songs she loves. Host a Mother's Day screening and serve popcorn and bowls Ghirardelli SQUARES like Milk and Caramel, Intense Dark 72%, or Creamy Almond Crunch.
For family and friends who can't make it to the big premiere, post the video on a private YouTube channel, Facebook, or another social media site.
A Hand-Painted Cookie Jar
Let kids paint their handprints and names (or any design they like) on a ceramic or glass cookie jar, then fill the jar with a fresh batch of chocolate chip cookies made with Ghirardelli premium milk chocolate baking chips.
A Lunch Box for Mom
It's the kids' turn to pack a lunch box for Mom. Fill it with picnic fixings for a fun afternoon outside or stock it with Ghirardelli SQUARES like Dark & Mint or Dark & Sea Salt Caramel to delight her for days to come.


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Stay Strong Britney
STAY STRONG BRITNEY! We believe in you! this group is only for...more»
We believe in you!
this group is only for people who want britney to get better. Who want her back on track again. Are you one of those poeple who want Britney to get better? then please, join this group. Lets show everyone that Britney deserves respect, love and support from us.
What happend to Britney? What was the reason that made this start? Is it because of Kevin? or what? who knows. but someone must help her. And in this group we gonna post news, photos and everything about her. and together with all the fans of Britney and together with poeple who cares about her we might can change Britney's mind. Its worth a try. Don't you think?
Britney is a rolemodel, a idol to many boys and girls around the world. She's a great mum and a great idol and rolemodel but poeple are pushing her, stressing her out and put alot of pressure on her. Why don't people give her some space? some privatcy? everyone needs some privatelife...
sorry for the bad english, but hope that you all understand what the group is about
- Would you hold it against me, if I'm Britney's #1 blog
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Britney Hits The Gym, Starbucks, Obviously
This is classic Britney. That ensemble, phone to ear, Starbucks in hand. Yep, that's Britney Spears, alright! Homegirl grabbed her caffiene fix in Westlake Village after hitting
Britney Flashes Her 10 Million Dollar Smile
She's a regular ol' Jackie Kennedy Britney's back home after performing two shows in Las Vegas this weekend, but not for long! The artsy fartsy singer
Mario Lopez Hooked Up With A Pop Star In Vegas
Britney Spears and Mario Lopez might've done the dirty. During his appearance on The Ellen DeGeneres Show, Mario revealed he had a one night stand with
Britney Does Something After Her Workout
Britney chats it up. After her workout, Britney changed into a white top and a pair of navy blue mom shorts for an outing with her
Britney Kicks Off October In Shape
Britney's back in the swing of things. After taking a few days off from her whirl-wind trip in Europe two weeks ago promoting The Intimate collection
Ed Sheeran Could Work (Bitch) With Britney Spears
Singer-song writer Ed Sheeran says he's a big fan of Britney's and is down to collaborate on her next artsy fartsy album. A fan asked Ed
Personal Britney Spears Interview Reportedly Confiscated
Britney's in hot water after a reporter's interview was confiscated and edited because it was too personal. A reporter for 2TV says she thought her interview
In a decade from now, Britney plans on getting married with two more kids, owning houses in Colorado, Miami and Vegas and filming three or
Britney's Home, Y'all
There's no place like home. After a crazy run in Europe promoting The Intimate collection, Britney is finally back home chillaxing before she gets ready for
Britney: I'll Do Music For Another 10 Years
Britney ain't going nowhere! In an interview with Germany's Bild, Britney opens about recording hits for another decade, the dark times in her past and and


text:
Metal wall panels are among the most widely used products in the metal construction and architecture industry. A 2008 survey by RSMeans, Kingston, Mass., shows the cost of metal siding panels is rising more slowly than the cost of most competitive siding materials. The cost of metal increased about 3 percent during the study's timeframe while the cost of exterior insulation and finish systems, stucco and tilt-up concrete increased 4.6, 5 and 10 percent, respectively. The installed cost of metal siding panels in 2008 averaged $7.66 per square foot, including all accessories and insulation. The average installed cost of competitive materials is at least 60 percent higher; single-wythe brick walls are nearly three times as expensive as metal panels.
There are three primary varieties of wall panels: insulated metal panels (IMPs), preformed panels and metal composite materials (MCM) panels. With IMPs, the foamed-in-place core fuses to the metal skins, expands to completely fill the interior cavity, then solidifies to create a solid, monolithic panel. At the end of this process, there are no gaps or voids and insulating values from R-14 to R-30 can be achieved depending upon the insulating core used and its thickness. Preformed metal wall panels are manufactured from a variety of metals, including steel, aluminum, copper and zinc, with steel being the most commonly used. A highly durable paint or coating is applied to steel panels to protect them from the elements. The smooth, sleek metal composite material can be bent, curved and joined together in an almost limitless range of geometric configurations. In addition, the panels exude a lustrous visual aesthetic when they are initially installed and continue to do so for years to come with minimal maintenance. There is no oil canning or wrinkling because the skins are bonded to the core under tension, which produces a balanced panel.
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In two weeks time I will host a workshop in Central London explaining how I create images like this. There are still a few seats left, so contact me or check my site for details: dracorubio.com/pages/workshop
So dark, great work man.Apr 20th, 2012 Reply
wonderful piece ♥Apr 18th, 2012 Reply
... WOW doesn't even begin to cover it ...Apr 18th, 2012 Reply
Beautiful textures! I love this!Apr 17th, 2012 Reply
Your art is very inspirational to all of us artists and at Shadowness we like to thank our amazing artists for all they do, to show our appreciation for you, your artwork has been featured in todays Daily Inspiration #408
Amazing workApr 17th, 2012 Reply
Wow! Stunning work !!!Apr 16th, 2012 Reply
thank you!Apr 17th, 2012 Reply
You'e welcome :)Apr 17th, 2012 Reply


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Developing Highly Engaged Students
Instructor: Shawn Gallagher
Grading: Letter
Spring, Summer & Fall (Ongoing)
Instruction Mode: Correspondence
Academic Level: K-12 Professional Development
NDSU Credit Fee: $350
Course Description:
Do you find your students are bored, inattentive, or disengaged during the day? This course will give you the tools to help your students lock in on learning. Based on current research, the text offers specific short and long term strategies to keep your students highly engaged. The ideas presented help students create a strong sense of self-efficacy. In short, this class gives you the blue print to make your classroom a place of learning, high energy, positive feelings, and even fun.
As a result of this participation in this course, students should:
- Analyze the current research in the area of student engagement;
- Generate activities that stimulate a students positive attitude toward learning;
- Assess strengths and weaknesses in the area of student engagement;
- Incorporate structured models that will extend student interest beyond the classroom;
- Synthesize activities and lessons to be taught in the classroom;
- Consider alternative ways to motivate students;
- Examine ideas for developing student self-efficacy;
- Incorporate specific strategies creating a positive educational environment for ASD students;
- Generate ideas for collaboration with other school staff.
The required reading is found in the text listed (enclosed with syllabus). The required text is: Marzano, R. J. (2011). The Highly Engaged Classroom. Bloomington, IN: Marzano Reasearch Laboratory
Jones, R. D. (2008). Strengthening Student Engagement. Rexford, NY: International Center for Leadership in Education, http://www.ipsi.utexas.edu/docs/alg_readiness_toolkit/Strengthen_Student_Engagement_white_paper.pdf
Kerr, A. & Grasby, R. (2009). Engagement through Choice: Using Independent Research Projects to Improve Student Interest. Journal of Classroom Research in Literacy, Vol 2, 3-19, http://jcrl.library.utoronto.ca/index.php/jcrl/article/view/5046/pdf_14
About The Instructor
Shawn Gallagher
Shawn Gallagher earned his M.A. in Education from St. Mary's State University in Winona, MN. Shawn has a B.S. in Elementary Education from St. Cloud State University. Shawn has over 17 years of experience teaching 3rd and 4th graders.
Special Instructions:
Texts/Readings are included in the total cost of the course.
**Registration Instructions:
A minimum $20 processing fee will be assessed per person for cancellations received after the start of the course. Refunds are not issued after the start of the course or after access to the course has been provided.


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About MyMind
MyMind was founded in June 2006 as a community based provider of accessible mental health services. We provide psychological and psychotherapy services to people who are seeking mental health support. Employing a combination of contracted and voluntary therapists and practitioners, we are able to offer accessible and affordable mental health care. Clients are able to self-refer to MyMind's service by booking appointments either online or calling the office on 076 680 1060, and due to the volume of mental health professionals we employ, appointments are usually made within 72 hours of their first contact with MyMind.
We are a non-profit organisation registered in Ireland (434008) with charitable status (CHY17600).
MyMind vision
Everyone in Ireland has easy and quick access to community based mental health services.
MyMind purpose
To pioneer a new and sustainable model of community based and online mental health services that are accessible and affordable to everyone.
MyMind's solution to current mental health situation in Ireland:
- MyMind is a self-referral model of mental health care
- MyMind is an alternative to the medical model – we do not prescribe drugs as a solution, only if necessary
- MyMind is easy to access, clients are able to see a professional within a few days after initial contact
- MyMind services are affordable, we also provide reduced or free sessions for those who cannot afford full fees
- MyMind provides one-to-one sessions, couple and family therapy, child and adolescent therapy, group therapy and workshops
MyMind is a Social Enterprise model
- Profits made from our fee-paying clients are used to support fees for clients who cannot afford it.
- MyMind connects clients with a team of qualified mental health professionals, ensures quality and adherence to regulations and standards.
Files to download:
Strategy plan 2014-16
- Maximise the potential of our existing early intervention MH services, by maintaining our average of 4.4 sessions per client
- Grow network of services: open a centre in Galway by Q3 2015
- Grow client base through marketing and partnerships with existing mental health organisations
- Reach financial break even by 2016
- Refine and consolidate evaluation and performance framework through improving performance reviews and client feedback forms
- Grow effective and efficient organisation: MyMind staff will provide the key skills and capacity that will enable the successful delivery of our strategic objectives
Operational Values
- We are relentless in our focus on creating easy access to mental health services across Ireland
- We define and follow procedures which support achievement of our goals
- We focus on solutions, not problems
- We ensure relevant stakeholders are involved in decision making processes
- We are committed to treating our clients with respect, professionalism and confidentiality
- We actively seek to partner with other organisations working in mental health
- We deliver a positive learning and development experience for our staff and volunteers
- We implement and follow policies and procedures to ensure vulnerable clients are protected from abuse
- We regularly review and assess the risks faced by MyMind in every aspect of our work and plan to manage those risks
MyMind Board of Directors
Eleanor Farrell (Chairperson - elected in 2011)
Head of Customer Base Management at Vodafone Ireland
Dr Paul Scully (joined in 2012)
Consultant Psychiatrist at St. James's Hospital
Eoghan Stack (joined in 2012)
Eoghan Stack is Director of Investment Impact for the One Foundation, building the effectiveness of One Foundation's portfolio organisations through strategy development, business planning, and performance management of portfolio organisations. Eoghan is responsible for leading One's investments in youth mental health and the integration of minorities. Prior to the One Foundation, Eoghan spent eight years with 3Com's R&D team designing integrated circuits and is an Electrical and Microelectronic Engineering graduate of University College Cork.
Michael Binchy (joined in July 2013)
Michael was called to the Bar of Ireland in October 2005 and since then he has represented many different clients in many different cases before Courts and tribunals. In addition to a varied general practice at the Irish Bar, he also lecture Solicitors for continuing professional development purposes on topics of current legal interest as part of the Solicitors CPD Group.
Ciara O'Toole (joined in December 2013)
Ciara O' Toole is an entrepreneur, marketing professional, author and pilot with an honours Bachelor of Commerce degree from University College Dublin and a first honours MSc in marketing from the UCD Smurfit graduate business school. Currently working with Social Entrepreneurs Ireland facilitating high potential social entrepreneurs to achieve maximum social impact. Founded The Cat's Pyjamas Strategic Marketing in 2004 and works on and off in a mix of contracts and consultancy work. Ex marketing manager of L'Oréal Paris Ireland comprising the L'Oreal Paris, Garnier and Maybelline brands, interim marketing manager of Red Bull, interim marketing communications manager of the Irish National Lottery, consumer planning director for Initiative Media working on the Diageo and Unilever accounts, marketing manager of Miller Genuine Draft, account director with Slattery Communications and brand manager for Johnson & Johnson. Holder of a private pilot licence for both land and seaplanes, earned at the Aero club of Como in Italy and Weston Airport Dublin. Fluent in Italian. Professional tennis coach. Author of travel narrative 'Going Solo on Lake Como'. Has travelled to more than 40 countries and lived in Australia, Italy and the US. Characterised as results-oriented and clear thinking with excellent written, creative, organisational and interpersonal skills. Proven track record of delivery against commercial and strategic objectives.


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Gear Question
There's no size chart. What kid shoe sizes...
Member since
There's no size chart. What kid shoe sizes do the small, medium, and large Keen socks fit?
Member since
i know. I noticed that. But with Backcountry's great return policy, i took the chance and ordered it anyway. it fit my two kids who wear a size 2/3 in shoes. Hope that helps.
View More Details on KEEN Yowie Crew Midweight Sock - Kids'


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BioShock is a critical darling that continues to be played and adored by roughly all of mankind, whereas Minecraft is a java-based creation game played by a niche cabal of super geniuses with either very boring desk jobs or tons of free time to kill. What happens when these two worlds collide? A fan made video that can only be described as scumtrulescent. Take a look:
Minecraft is fast becoming the fanboy creation tool of choice. Considering the sheer amount of time and sweat poured into this particular video, this is an absolute testament to BioShock's imprint on gaming.
Oct 21, 2010
Minecraft player builds amazing, horribly confusing, working computer in blocktastic game
And his creation is so impressive, he got a job offer out of it
Fan Art versus Official Art
A showdown between fan-made creations and their official counterparts
Fable demake goes 8-bit 2D, fixes Molyneux's mistakes
Yeah. We're talking acorns.
Spartan523 - November 30, 2010 3:46 a.m.
michaelizzo - October 22, 2010 6:19 p.m.
BishopofHippo93 - October 22, 2010 12:06 a.m.
hardcore_gamer1990 - October 21, 2010 11:57 p.m.
ThatGuyFromTV - October 21, 2010 11:35 p.m.
BriefCandle - October 21, 2010 11:22 p.m.
RFswitchBlade - October 21, 2010 9:41 p.m.
GamesRadarMichaelGrimm - October 21, 2010 9:39 p.m.
PlainLikeVanilla - October 21, 2010 7:49 p.m.
Evil_AppleJuice - October 21, 2010 7:37 p.m.
ChipTheExecutioner - October 21, 2010 7:15 p.m.
BrunettePride - October 21, 2010 7:13 p.m.
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