Diagnostic Pathology Histology, imaging and new diagnostic work-flows in pathology

John Gilbertson firstname.lastname@example.com
The Pathology Service
Massachusetts General Hospital
BostonMAUSA

Yukako Yagi
The Pathology Service
Massachusetts General Hospital
BostonMAUSA

Diagnostic Pathology Histology, imaging and new diagnostic work-flows in pathology
10.1186/1746-1596-3-S1-S14BioMed Central Page 1 of 3 (page number not for citation purposes) Proceedings * Corresponding author
Introduction:Since their introduction in 1999, fully automated, high speed, high-resolution whole slide imaging devices have become increasing more reliable, fast and capable. While by no means perfect, these devices have evolved to a point where one can consider placing them in a prediagnostic role in a clinical histology lab.Methods:At the Massachusetts General Hospital, we are running a pilot study placing high end WSI devices in our main clinical histology lab (after the cover slipper and before slides are sent to the pathologist) to examine the requirement for both the machine and the laboratory.Results: Placing WSI systems in the clinical lab stresses the system in terms of reliability and throughput. Significantly however, success requires significant modification to the lab workflow. It is likely laboratories need to move from manual, large batch processes to increasingly automated, continuous flow (or mini-batch) processes orchestrated by the LIS using bar coding to track and direct slides, and incorporating the decision to image into the specimen type and the histology orders. Furthermore, image quality, capture speed and reliability are functions of the quality of the histology presented to the WSI devices.Conclusion: Imaging in pathology does not begin in a WSI robot but in the grossing room and in the histology lab. As more and more imaging devices are placed in histology lab, the interrelationships histology and pathology imaging will become increasing understood.

Introduction

Fully automated, high speed, high-resolution whole slide imaging (WSI) systems have been available for about 8 years [1]. The early development of these systems focused on the basic technical issues surrounding the creation of high quality images at reasonable speed and the management and display and the very large data sets they created. While these issues have by no means been completely solved, multiple companies around the world are now producing effective systems based on traditional microscope optics as well as more radical designs [2]; investigators have demonstrated that, in some situations, pathologists examining images rapidly captured by fully automated WSI robots can make diagnoses that are as correct and as complete as those made directly from the glass [3]. However, the WSI experience is not yet as good as that from 9th European Congress on Telepathology and 3rd International Congress on Virtual Microscopy Toledo, Spain. 15-17 May 2008 of the microscope (diagnostic capability is a poor proxy for image quality) and serious problems with WSI diagnosis have been reported in some specimen types [4]. That said, the progress in whole slide image capture has been remarkable given the technical issues involved, and we expect further improvement in the future, both through general, relentless growth of technology driven by Moore's Law and new microscope optics, stage and camera designs specifically for WSI.

While the technical issues surrounding WSI are challenging and fascinating, to be successful, WSI must be a useful tool to enhance pathologic examination of tissue. If we can successfully digitize our slides, we can apply computational power and network connectivity, the drivers of productivity in modern world, to the analysis of tissue morphology and the practice of anatomic pathology. With reliable -if not perfect -systems available, we can now turn to the question of how large scale WSI can be implemented in Pathology practices.

This paper is about our initial attempt of implementing WSI in the clinical histology laboratory -and the somewhat surprising things we discovered.

Methods

Today, the majority of WSI work (at MGH and elsewhere) is "post-diagnostic" in that they occur after the pathologist has used the glass slide to make the diagnosis. They include conference support, teaching, research (especially support of morphologic, immunohistochemistry molecular analysis and tissue banking). Other institutions have reported at least pilot studies in surgical pathology QA [5]. These applications make sense, as early development targets because they do not place the whole slide image in the role of primary diagnostic medium, tend to involve lower slide volumes and less time stringency. The slides are made in histology, sent to pathologist for diagnosis and are then sent to the "slide room' for management after sign out, and the WSI operation is placed in (or associated with) the slide room. In our experience, basic infrastructure that makes the applications work well include bar coding with readers in histology, slide room and on the imagers, a standard imaging request mechanism and skilled imaging technicians.

Our main interest however, has been in the pre-diagnostic area. Well-known applications in this space include "virtual" distribution of control slides and immunohistochemistry slides [6]. However, the most important prediagnostic situation would be placing WSI robots in the clinical histology lab and incorporating specific imaging protocols (and image analysis) in specific histology protocols for specific specimen types. This would greatly increase the volume (and value) of WSI and would drive further investment and investigation. This activity is at robust pilot phase at MGH.

Results

When one places a WSI robot at the end of the slide creation process in clinical lab (after the cover slipper and before slides are sent to the pathologist), one puts a number of stresses on the system. In particular, the system must be reliable (at least as reliable as the rest of the histology lab), and it must be fast (at least fast enough to keep up with the throughput of the lab). This merges the performance of the imager to the performance of the lab. For example, if the lab organized to generate a bolus of 500 slides at nine AM, no device, no matter how fast, will be fast enough. On the other hand, if a lab is organized to generate a continuous flow (or mini-batches) of 15 slides every 15 minutes. Modern, high end imagers can "keep up" with this flow with minimal delay of slide delivery to the pathologist if a subset of cases is presented to the imager based on specimen type and processing rules and if the slides are well made (see below).

Placing a WSI robot in a clinical histology lab quickly demonstrates a necessary symbiosis between histology and imaging. The histology lab plus the WSI robot need to be considered as single imaging device, or, to put this another way, the WSI robot needs to be considered as just another automated histology device (like a processor, stainer or cover-slipper). WSI robots need to be reliable and fast (a large number of slow devices might work, but most histology labs have limited space), but laboratories will likely need to change to automated, mini-batch processes orchestrated by the LIS use bar coding to track and direct slides and incorporating the decision to image into the specimen type and the histology orders.

There is another interaction between imaging and histology that possibly more imaging robots create better images, and create them faster and more reliably, if they are presented with high quality tissue slides. In other words, the quality of the image is a function of the quality of the slide. The histology parameters of tissue placement, the flatness and thinness of sections, their staining, and the quality of cover slipping and label placing all affect image quality, capture speed and reliability. There are good reasons for this, details will be presented by Dr Yukako Yagi at her scientific presentation and paper at this conference. Imaging and Histology are two faces of the same thing -they cannot be meaningfully separated.

Conclusion

Imaging in pathology does not begin with WSI robot but in the grossing room and histology lab. As more and more imaging devices are placed in histology labs, the relationships and histology parameters such as fixation, cutting and staining, and imaging parameters such as illumination and dynamic range will become increasingly studied and, over time, will allow us not only to take better pictures, but to actually see more detail and structure.
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AcknowledgementsThis article has been published as part of Diagnostic Pathology Volume 3 Supplement 1, 2008: New trends in digital pathology: Proceedings of the 9th European Congress on Telepathology and 3rd International Congress on Virtual Microscopy. The full contents of the supplement are available online at http://www.diagnosticpathology.org/supplements/3/S1Publish with Bio Med Central and every scientist can read your work free of charge http://www.diagnosticpathology.org/content/3/S1/S14
Clinical slide digitization -whole slide imaging in clinical practice [chapter. J R Gilbertson, A A Patel, Y Yagi, Virtual microscopy and virtual slides in teaching. J, Ogilvie RW. Taylor & Francis, Boca RatonGilbertson JR, Patel AA, Yagi Y: Clinical slide digitization -whole slide imaging in clinical practice [chapter]. In Virtual microscopy and virtual slides in teaching, diagnosis and research Edited by: Gu J, Ogilvie RW. Taylor & Francis, Boca Raton; 2005.

Critical comparison of 31 commercially available digital slide systems in pathology. M García-Rojo, G Bueno, J González, M Carbajo, Intern Journal of Surgical. PathologyGarcía-Rojo M, Bueno G, González J, Carbajo M: Critical compar- ison of 31 commercially available digital slide systems in pathology. Intern Journal of Surgical, Pathology 2006:14-26.

Primary histologic diagnosis using automated whole slide imaging: a validation study. J R Gilbertson, J Ho, L Anthony, D M Jukic, Y Yagi, A V Parwani, BMC Clin Pathol. 64Gilbertson JR, Ho J, Anthony L, Jukic DM, Yagi Y, Parwani AV: Pri- mary histologic diagnosis using automated whole slide imag- ing: a validation study. BMC Clin Pathol 6:4. 2006 Apr 27;

Feasibility and diagnostic agreement in teledermatopathology using a virtual slide system. C Massone, Peter Soyer, H Lozzi, G P , Di Stefani, A Leinweber, B Gabler, G Asgari, M Boldrini, R Bugatti, L Canzonieri, V Ferrara, G Kodama, K Mehregan, D Rongioletti, F Janjua, S A Mashayekhi, V Vassilaki, I Zelger, B Zgavec, B Cerroni, L Kerl, H , Hum Pathol. 384Massone C, Peter Soyer H, Lozzi GP, Di Stefani A, Leinweber B, Gabler G, Asgari M, Boldrini R, Bugatti L, Canzonieri V, Ferrara G, Kodama K, Mehregan D, Rongioletti F, Janjua SA, Mashayekhi V, Vas- silaki I, Zelger B, Zgavec B, Cerroni L, Kerl H: Feasibility and diag- nostic agreement in teledermatopathology using a virtual slide system. Hum Pathol 2007, 38(4):546-54.

Use of whole slide imaging in surgical pathology quality assurance: design and pilot validation studies. J Ho, A V Parwani, D M Jukic, Y Yagi, L Anthony, J R Gilbertson, Hum Pathol. 373Ho J, Parwani AV, Jukic DM, Yagi Y, Anthony L, Gilbertson JR: Use of whole slide imaging in surgical pathology quality assur- ance: design and pilot validation studies. Hum Pathol 2006, 37(3):322-31.

Evaluation of whole slide image immunohistochemistry interpretation in challenging prostate needle biopsies. J L Fine, D M Grzybicki, R Silowash, J Ho, J R Gilbertson, L Anthony, R Wilson, A V Parwani, S I Bastacky, J I Epstein, D M Jukic, Hum Pathol. in pressFine JL, Grzybicki DM, Silowash R, Ho J, Gilbertson JR, Anthony L, Wilson R, Parwani AV, Bastacky SI, Epstein JI, Jukic DM: Evaluation of whole slide image immunohistochemistry interpretation in challenging prostate needle biopsies. Hum Pathol 2008 in press.


Narratives of violence: the micropolitical dimension of emotions Narrativas da violência: a dimensão micropolítica das emoções

Maria Claudia Coelho
Narratives of violence: the micropolitical dimension of emotions Narrativas da violência: a dimensão micropolítica das emoções
Translated by Luiz Costa Translation from Mana, Rio de Janeiro, v. 16, n. 2, p. 265-285, out. 2010.EmotionMicropolitics of EmotionUrban ViolenceContemptSympathy
This paper analyzes the emotions described in narratives of victimization among Rio de Janeiro's middle classes. It explores the so-called 'contextualist' trend (Lutz &  Abu-Lughod 1990)  in the anthropology of emotions as a means to understanding violence, focusing on the micropolitical dimension of emotion discourses on victimization. The data analyzed is derived from eight in-depth interviews with married couples who have been through the experience of having their residences assaulted while both of them were at home. The analysis focuses on the recurrence of two emotions in the interviewees' depictions of their feelings towards their assailants: sympathy and contempt. The emergence of these two emotions, whose relations to hierarchy have already been well documented by social scientists, is interpreted as an attempt to re-establish the hierarchies perceived to have been overturned by the assaults.RESUMOEste trabalho tem por objetivo examinar as emoções presentes em relatos de experiências de vitimização em segmentos das camadas médias do Rio de Janeiro. A proposta é explorar a fecundidade da vertente "contextualista" (Lutz & Abu Lughod 1990) da antropologia das emoções para a compreensão da violência, com foco na dimensão micropolítica dos discursos sobre as emoções ligadas à vitimização. Os dados analisados são um conjunto de oito entrevistas em profundidade realizadas com casais que passaram, marido e mulher, pela experiência de terem suas residências assaltadas enquanto estavam em casa. A análise está focada na recorrência de duas emoções presentes nas descrições que os entrevistados fazem de seus sentimentos em relação aos assaltantes: compaixão e desprezo. A emergência destas duas emoções, cujas relações com a hierarquia já foram apontadas pelas ciências sociais, é então interpretada como uma tentativa de restabelecer hierarquias que teriam sido ameaçadas pelos assaltos.Palavras-chave: Emoção, Micropolítica das emoções, Violência urbana, Desprezo, Compaixão.

Introduction

This article discusses the relationship between morality, alterity and violence, taking as its object of analysis the feelings manifested in reports of the experiences of victimization in a specific modality of urban violence: home burglaries. It contributes to the anthropology of emotions, engaging with the theoretical strand of "contextualism" (Lutz and Abu-Lughod 1990) and its emphasis on the micropolitical dimension of emotions.

The middle classes of Rio de Janeiro are the social universe under analysis. The method is that of the detailed interview. The data are a set of eight interviews with three couples who lived through experiences of residential burglaries; and with two women who also had their residences burgled while they were at home, in the company of their husbands and/or their children, maids, etc. i The three men interviewed are 84, 55 and 43 years of age; their wives are, respectively, 85, 52 and 42 years of age. The other two women are 66 and 50 years old. All have children: the first couple has ten, the second has two and the third has one; each of the two women has two children. The first couple live in a middle class neighbourhood in the northern zone of the city, the second in the southern zone and the third in Barra da Tijuca. The two women live in neighbourhoods of the southern zone of Rio de Janeiro. Among the men, one is a retired civil servant, another is an engineer and the third is manager of a multinational company; among the women three are housewives, one is a marchand and the other a businesswoman.

The article explores the existence of a standard narrative of these experiences, focusing on the characterization of the burglars and on the feelings that they elicit in the interviewees. To this end, it is structured in three sections. The first makes explicit the theoretical presuppositions that guide the analysis, in particular: a) the main strands of the anthropology of emotions according to the scheme proposed by Lutz and Abu-Lughod (1990); b) the existence of a micropolitical dimension to emotions, by which it is meant the capacity of emotions to actualize, in the subjective experiences of individuals, aspects of the macro level of social organization.

The second section examines the narratives of the interviewees, focusing on their representations of the burglars, particularly their attitudes and attributes. It seeks to track the associations between "disorder", "filth", "poverty" and "ignorance". The third part analyses the feelings elicited by the experience of victimization, establishing the existence of a dynamics relationship between humiliation/fear/impotence, on the one hand, and rage/contempt/compassion, on the other.

Emotion as an object of the social sciences: an outline of the field

In the United States, the anthropology of emotions underwent a marked development during the 1980's with the publication of a text which is now an obligatory reference in the field: Michelle Rosaldo's (1984) work on the anthropology of affects, influenced by the interpretativistic view of Clifford Geertz. ii Based on ethnographic comparisons of data obtained during fieldwork among the Ilongot, Rosaldo affirms that it is the task of anthropology to show how culture (understood in its public and symbolic dimensions) interferes in the psychological experience of individuals. Her central point is "the recognition of the fact that feeling is forever given shape through thought and that thought is laden with emotional meaning" (Rosaldo 1984: 143). In attempting to clarify the boundary between thought and feeling, Rosaldo suggests that the key distinction is the form of the involvement of the social actor's self. It is from this distinction that she extracts her well-known definition of feelings as "embodied thought": "Emotions are thoughts somehow 'felt' in flushes, pulses, 'movements' of our livers, minds, hearts, stomachs, skin. They are embodied thoughts, thoughts seeped with the apprehension that 'I am involved'. Thought/affect thus bespeaks the difference between a mere hearing of a child's cry and a hearing felt -as when one realizes that danger is involved or that the child is one's own." (Rosaldo 1984: 143) Rosaldo thus concludes by affirming that feelings are social practices, structured through ways of understanding and conceiving of the body, affects and the person. As these concepts are culturally determined, she is led to doubt the supposed universality of emotions (ibid: 143).

This perspective, the essence of which can be defined as a belief in the culturally constructed character of emotions, also guides Lutz's (1988) reflections on Euro American conceptions of emotions, which are abstracted from an effort at understanding Ifaluk emotions through an auto-reflexive movement that is typical of the anthropological endeavour. Lutz outlines a detailed framework for Euro American ways of conceiving the emotional dimension of human experience, for which the key opposition is that between emotion and thought.

This opposition is said to emerge in Euro American thought in different guises: in the academic world, as affect/cognition; in a romantic version, as an opposition between reason and passion; and in common sense, as feeling/thought. These oppositions share a common trait: they are the most authentic realities of the individual, more authentic than speech or other forms of interaction. They are the space where the true self emerges.

The fundamental axis around which Lutz elaborates this Euro American conception of emotions (what she terms "ethnopsychology") is a pair of terms in relation to which emotion is opposed: thought and estrangement from the world. In relation to thought, emotion is situated in the negative pole, with thought being the valued form; in relation to estrangement from the world, emotion is the positive pole, with distance being avoided.

The work of Rosaldo and Lutz, which seeks to theorize emotional phenomena through a comparison of distinct ethnographic material, are representative of the line of studies that Catherine Lutz, a few years later, would characterize as the "relativistic" strain of studies of emotion. This strain departs from a belief in the existence of any essential aspect to emotions, which are rendered cultural constructs of an evidently variable nature.

Along with two other approaches to the study of emotions, this relativistic strain is a part of the scheme of ways of thinking about emotion delineated by Lutz and Abu-Lughod (1990) in their introduction to a volume of studies of emotion. The authors note the existence of two other approaches: the essentialistcharacterized, as the name suggests, by the conviction that emotions are universal facts that stem from intimate individual experiences, and which are refractory to any sociocultural configuration -and the historicist, which shares with relativism the conviction that emotions are cultural constructs, but which understands these constructs in a diachronic dimension.

Against the background of this scheme, Lutz and Abu-Lughod propose a contextualist perspective, which is theoretically inspired by Foucault's notion of discourse, understood not as speech that establishes a referential relationship to something that is exterior to it, but rather as speech that gives form to that about which it speaks. This perspective allows the authors to engage with the micropolitical dimension of feelings, showing how emotions are dependent on relations of power between social groups, simultaneously expressing and reinforcing these relations.

Lutz's chapter in the volume is an example of this perspective. She returns to her study of the role of emotion in Western thought through the idea that "any discourse on emotion is also, at least implicitly, a discourse on gender " (1990: 69). In this chapter she focuses on the existence of a "rhetoric of control" of emotions associated with gender, which, in her view, makes any discourse on emotions also a discourse on the exercise of power.

Basing herself on a set of interviews conducted with middle and working class North American men and women, Lutz develops an analysis of how the theme of the control of emotions emerges in the discourse of men and women. Her starting point is a paradox that she identifies in Western emotion talk: they are at the same time "signs of weakness" and a "powerful force". This paradox is at the centre of the ambiguity surrounding the condition of women in Western thought: "emotionality is the source of women's value, their expertise in lieu of rationality, and yet it is the origin of their unsuitability for broader social tasks and even a potential threat to their children" (1990: 77).

Lutz furthermore suggests that there is a parallel between this way of understanding the female condition and Taussig's (1984) study of colonialism, which highlights the ambiguity of the colonizer's view of Indigenous peoples, in which fear and fright alternate with disgust and disdain. For Taussig, this is a process in which the "colonial mirror" "reflects back onto the colonists the barbarity of their own social relations" (Taussig 1984: 495 in Lutz 1990. Through this comparison, Lutz envisages the possibility that a "paradox of will" is a recurring aspect of relations of domination:

"A 'paradox of will' seems consistently to attend dominating relationships -whether those of gender, race, or class -as the subordinate other is ideologically painted as weak (so as to need protection or discipline) and yet periodically as threatening to break the ideological boundary in riot or hysteria. Emotion talk, as evident in these transcripts, shows the same contradictions of control, weakness, and strength. Given its definition as nature, at least in the West, emotion discourses may be one of the most likely and powerful devices by which domination proceeds." (Lutz 1990: 77-78).

The theme of the relation between emotion and power is at the centre of other studies, produced by social scientists of various intellectual traditions, that seek to understand the micropolitical dimension of specific feelings, showing how the grammar of the emergence and expression of feelings can shed light on the "macro" level of social organization. In the following sections, I will seek to understand the feelings narrated by the interviewees -particularly sympathy and contempt -with the help of studies that attempt to understand this micropolitical capacity of emotions.

Representations of the burglars

The descriptions of the burglars by the interviewees reveal a recurrent aspect: the disorganized and chaotic nature of their attitudes. In many statements, the actions of the burglars are collectively characterized as "agitated", "disorganized" and a "mess":

But they were two first-timers. I suspect that they were not from [coastal town]. I suspect that they, being in these trends […] these idiotic parties by the sea, that do those things, that filth, that constant murmur, everyone does what they want in the middle of the street, it's a right mess at this time (Rafael). iii We have sliding closet doors. So all we heard was this noise, ploft, ploft, because there are rooms there, and everything was like a tremendous noise, then we heard tearing of those sheets which are like nylon, also, which aren't pure cotton, and I kept saying "my God, what is this"? (Magnólia) Then I got mad, you see, about them being there, tossing cigarettes on the floor, you see, making a mess, tearing all those clothes, taking my coat which I loved, which my husband gave to me on our honeymoon… (Joana) This representation of the burglars can sometimes exceed the level of "disorder", being characterized as "filthy", as in Rafael's narrative above, or in this dialogue:

Then they took too long. Because they even ate, they opened the fridge, made a total mess, a lot of noise. Filthy, right? (Magnolia and Rafael).

At other times, when they are characterized individually, an opposition is also frequent: the "agitated" versus the "calm", with "agitation" being often associated with drug use. Here are a few examples:

But… yeah… in specific terms, there were four burglars, with the clear leadership of one of them, which was a level-headed chap, who came in armed but, once he saw that the situation was under control, he hid the gun.

What did he do?

Gave it to the other, I don't remember anymore, but he wasn't armed. And a madman, completely off his head, which went around with two guns, changing TV channels with the barrel of the gun, you see… (Luís).

What do you remember of them?

What age more or less? Ah… they were all very young. One… there was the boss, which was more well-kept, which was in fact very well dressed, which was a dark person, like, handsome, thin, he wasn't like… thin, tall, handsome, a good-looking chap… he was calmer. He was in charge.

[…] I saw four. Ah, there were four inside, but there was another outside that, I don't know… I'm wrong, there were five burglars, OK, at the time, but those that were inside with us, they were more agitated, except for the boss. They were agitated, they smoked, they kept saying "we have nothing to lose", and kept laughing, nervously (Joana).

And they were three. Two were, like, quite presentable, and there was the older one, who looked sort of doped up, he is very agitated, and then they wanted more things. I said: "No! We don't have jewels, we don't have anything", right? And then… We saw that they were going through the whole house, right? (Vânia)

The others were bad. They put the gun right "here", stuck the gun to your head. This one never did that. The one that did it to me put it here from far and then turned, but I felt that he wasn't doing that… He wasn't going to do it, that's what he was sending me. For some reason, I trusted him more. And he wasn't high. One was certainly high. The other two, no. One was very calm (Ana).

I think the most aggressive one stood out.

[…] The more organized one said that if we behaved everything was going to be alright; during the burglary they didn't act this way. You get it? So, he implied that everything was going to… it was going to be a straightforward burglary, but they didn't refrain from intimidation, nor from threats, not even I think from the violence of tying us up, of shoving a gun against our heads. I think… So, I think that the difference between them was in their function, I think. Personality, perhaps the youngest was more aggressive, right? (Guilherme)

In this section, I have reproduced a sequence of passages, taken from the statements of seven out of the eight interviewees, in order to highlight the theme of "disorder" in the interviewee's characterizations. "Disorder" is sometimes associated with "filth", in a symbolic tie that evokes Douglas' (1976) classic conception of "dirt" as something that is "out of place". This description of the attitudes of the burglars also brings us to Caldeira's (2000) discussion of violence as "disorder", clearly identified, in its universe, as a rhetorical strategy that always begins by describing how violence suddenly irrupts in daily affairs, disrupting it. iv A second trait clearly associated with the burglars is their poverty:

All were like middle class, there was only one who was… a little, perhaps, C-class, like, poorer, but they weren't any people that you could say: "No! They are people in need, they came, they were born... in a very difficult situation". I couldn't notice this, they all had, maybe they even had an education, they recognized a Monet engraving.

Do you think it would have made any difference for you? Yeah… this way it would have surprised me less. I think the difference was the surprise of noticing that they were people with at least basic education. The boss may even have had higher education, right? He hadn't finished, but he was there. Taking his courses… It would've been… I would've been less surprised, found it more rationally justifiable. Hell! The person needs it! But that wasn't the case. The difference would've been more being surprised by my expectation that people who rob are people… truly in need, who come from a very difficult situation, who have had no opportunities in life, and crime would be a rational consequence of this… this environment in which they lived, right? But at no time did this seem to be their situation, right? One of them, even, had lived practically over there in [street of high-end residences] and so on (Guilherme).

Guilherme's narrative makes explicit an expectation which, in the other statements, emerges in a veiled form: the association between criminality and poverty, with material needs being conceived as a fundamental motivation for the decision to commit burglaries. This association is more subtle in other reports, occasionally linking poverty, criminality and "favela" or "suburbs" in a relation which is otherwise recurrently established in the common sense of middle and upper class residents of Rio de Janeiro:

[…] it was an upper middle class gang. I mean, two of them were upper middle class. None was from a favela, the other two were… middle class… one of them lower middle class and the other poor, but none of them lived in favelas. […] this was the only black one of the situation, the other was even a mulatto, the other one who was downstairs; one of them was [mulatto] and the other was white. And… one was from [street of high-end residences] (Ana)

[…] my fear was that I saw myself this way, thrown in some random suburb, raped, being shot, or dead. I visualized it in my head: me tossed in some hole somewhere… (Joana).

This association between violence and differences in social class emerges from the narratives in a further, even more subtle, way: in speculations as to why their residences were chosen for acts of burglary. In many narratives, the interviewees offer clues that they suppose that people who had carried out some work in their homes -symptomatically work that requires little qualification and offers low wages, such as cleaning, gardening or construction -had, intentionally or inadvertently, passed on information to people of the same social environment (defined by income and/or place of residence) that they were acquainted with, thereby fostering "envy" and making them targets for burglaries. Here are some examples of this logic:

Because this chap who was a cleaner, he had taken his holidays and on that day a new fellow had begun to work for a month, and the superintendent simply hired the boy without even seeing him, […] no one knew him, no one had seen him. We imagine that there may have been something with him. It has to be, right? (Vânia).

While the other [another burglary in which she had been a victim], I knew that they had studied our home, they knew that there must be something there, I thought it had to do with the maid, because maids love to say that one employer has more than the other. She must have said something […] because there was a maid who worked in our home […] who was very impressionable… you see? So I thought that there, at mom's house, they knew that there was something (Joana).

There was something… we had carried out some major improvements in our home, and we hired a… how should I say it?... a foreman. And we stayed here while the housekeeper stayed there. So, the housekeeper said that the house was full of cleaners, that it was just general cleaning, painting inside, outside, that stuff, right? And the housekeeper said: "ah, these two boys, I think they worked here, because their body type was the same as the boys who worked here". But we have no knowledge or certainty of this now (Magnólia).

And we had yet another problem: we called a man to get coconuts, because we have some coconut palms in our house. And this man brings a boy, about 13, but a dwarf, but 13, to help carry the coconuts and all that stuff. And as it happens our dog was let loose in the yard in front of them, because the dog is very obedient, we just call and he answers and all that. At a certain moment… first, Rafael tends to put his money in his pocket without a wallet, without anything. And if he has to pay for something, a taxi, or offerings at the church, or any payment, he pulls out this wad of cash and sieves through it. The coconut man saw when he went to pay, the boy saw it. And at some point when someone, I don't know who, said something about the dog and the boy said, "ah, this dog is nothing". So we had this problem that [in the house in which they were] there was an elderly couple, a dog that is nothing and a man who has money in his pockets. This must have spread… I mean, this is what I think, right? And I spoke to some of our sons and they all think that there may have been a… not those who went to our house, but they may have spoken to others from [neighbourhood in coastal town], that it has something with the Baixada v … What is this neighbourhood, is it a middle class neighbourhood? No, no. Sort of, there are many… some favelas. More necessitated. Yes, there is commerce… Lots of commerce. But it is a middle class much, much lower and others… (Magnólia and Rafael).

This sort of explanation for this modality of violence, linked to a cleavage between social classes, acts in conjunction with an association between criminality, poverty and place of residence. This is particularly clear in the last statement, in which the couple imagine the existence of a network of contacts between people who live in a neighbourhood of a coastal city where there are "favelas" and the Baixada Fluminense, and where these people may have had access to information of a purported "wealth" attributed to the couple by a man who carried out gardening in their home. This logic seems to link these statements to the "despotic" discourse on violence, following Soares and Carneiro's (1996) typology, which, as one of its characteristics, postulates the existence of urban foci of violence, primarily identified with the favelas.

The third and final characteristic trait of the representation of the burglars is the ignorance that the interviewees attribute to them. This ignorance, however, is not as explicit as their poverty, the disorder and filth. It is not explicitly stated, but is rather suggested in derogatory, often ironic, comments offered in passing:

Now, that they've sold it, they must have sold it for anything… they must have sold it, because there are things that have value and things that don't, right? Specially me, since I work with these things, with antiques, even with jewellery, I don't know what… Sometimes you look at a wedding, all the women with wonderful jewellery; some are worth a lot, others are worth nothing, but they all have the same effect, it's a jewel that has carbon, the other doesn't… Do you thing they sold it for anything because they were unaware of its value, because they did not know how to sell I think because they do not know their values, and also because they must subject themselves to selling to dealers who are not good dealers, who are people who are also thieves, and who will buy and make money from them (Joana).

Everything I remembered that I had I thanked God. Some they wanted, some they didn't, right? So… they were amazed by silly trinkets, for example, a backpack from [name of store], luggage. No one saw it because Guilherme never used these things. They found it beautiful and wonderful, they took it. And other things, which were perhaps even more valuable, they didn't take, like a [name of brand] watch, golden.

They didn't see it?

They saw it, I handed it to them, but they didn't want it, didn't get it, so… (Ana).

Ah, there is an interesting thing, when I had to go to my room to show my things I could tell them that there was a gun -I had a revolver that I kept under my bed, in my place, on my side. So I showed them the revolver, pointed them to it, and they went to get it; at this stage there was him and me in the room, one on each side of the bed. He then took my gun, put it in the middle of the bed and said: "let's see who's faster", his on his belt, stuck to his trousers. I said: "I'm not going to do this, it's not my métier". I later regretted this, because I had to explain to him what métier is, you see? (Luís) Then they started going through the things, got my ID card. I was a civil servant at the time and had a special card. I said "I'm screwed", but fortunately they were illiterate. The way he looked and looked at the card and said: "you must be one of those who speak to [the president of Brazil] anytime you want to". (Rafael).

These passages allow us to glimpse an attempt to establish superiority in relation to a cultural level that is perceived to be inferior: the burglars are illiterate, have a limited vocabulary and are incapable of recognizing the value of the things they want to burgle. This suggests that there is an element of contempt towards the burglars -a feeling that brings us to the next part of this article.

The Feelings of the Interviewees

The statements are permeated by expressions relating to the emotional experiences of the interviewees during the burglaries. Contempt, insinuated in the passages that allude to the purported "ignorance" of the burglars, is more explicit in other passages, in particular in those in which the interviewees make comments that accentuate their economic superiority.

[…] he said to me [assumes a harsh tone]: "gimme your cell phone!". Then I, so as to not lose my phone, he hadn't searched me, got my cell phone from my pocket, gave it to him. A beautiful cell phone. A gift from her to me. Now I have one which is rubbish. Great. When I hand this phone over to a thief he will say, " Poor chap. Doctor, keep it" [laughs]. "I don't want this". (Rafael)

The only thing they took from [the daughter] was the cell phone's chip, that's all! So that we couldn't communicate. They went: "her cell phone is much worse than mine!". Then, Guilherme, at this time we thought, I though: "mine is bought, yours is stolen, but that's alright!" (Ana).

[…] they said like this: "Yeah, these people here, this middle class building, they don't have anything!". I went: "Yeah, there is really nothing, son. My husband is a civil servant. What does a civil servant make? If you want to rob somewhere with money, you should look for a place that has people with money; here in the building everyone is this way, everyone is hard up. You're not going to find anything worth a million here". I said to him [laughs] (Vânia).

The ironic way that the interviewees report these moments of the burglaries, their internal dialogues, their playfulness, suggest the existence of a sort of delight in proclaiming that they own little. This is why Rafael laughs when he imagines the "pity" that a thief would feel upon seeing the poor quality of his cell phone; it is why Ana, in an internal dialogue, replies to the burglar's observation concerning the poor quality of her cell phone by stressing that she had the means to acquire it; and why Vânia takes pleasure in reproducing the conversation in which she informs the burglar that she owns nothing of value. But in what way is an admission of lowly possessions in relation to those of others also an affirmation of a hierarchically superior position? I stress "admission" because it is evident, from other parts of the statements (including those reproduced above concerning the "poverty" of the burglars), that the interviewees' understanding of the differences in buying power between themselves and the burglars attributes to them, the victims of burglary, a higher status. What, then, is the subjective work done by this self-admission?

In his classic study of the gift, in the midst of a profusion of ethnographic data Mauss (2003) analyses the potlatch ritual, found among the tribes of the American north-west. In the potlatch enormous quantities of material wealth are destroyed in an effort at constructing social prestige and obtaining power by means of material detachment: if I destroy it is because I can dispose, and if I destroy more, it is because I have more, and therefore I can do more and I am more. The interviewees, thus, by laughing at an inference concerning their own destitution, reaffirm their position of hierarchical superiority: "I have more than you and I am so secure of this fact that I do not need to ostentate, nor do I allow myself to be affected by your inference that I have little": this is what the interviewees seem to be realizing at the level of discourse, in a sort of discursive potlatch.

Ursula synthesizes this general "climate" by saying that, unlike the burglars, she needs to take care of her life because she has much to lose: "And I don't react to burglaries because I think I have a lot to lose. They have nothing to lose, right?".

These comments, along with those concerning the "ignorance" of the burglars, suggest the recurrence of a feeling of contempt on the part of the victims towards those who steal from them. In a study of feelings of disgust and contempt, Miller (1997) defines them as "emotions that demarcate status". Referring specifically to contempt, Miller identifies it as mechanism that is equally capable of creating or contesting hierarchies, wherein lies its political importance. The author thus expresses his view of the micropolitical capacity of contempt:

"Contempt is the emotional complex that articulates and maintains hierarchy, status, rank, and respectability. And differentiated status and rank are the eliciting conditions of contempt. So what we have is a kind of feedback loop in which contempt helps create and sustain the structures which generate the capacity for contempt. And there is good reason to believe that the particular style of contempt will be intimately connected with the precise social and political arrangements in which it takes place. " (Miller 1997: 217) Basing myself on Miller's analysis of contempt's potential to establish hierarchy, I can point to an initial trait of the emotional dynamics that marks the experiences of victimization under analysis in this article: an effort at recovering, through this feeling, a place of hierarchical superiority on the subjective level.

Contempt, however, is not the only feeling capable of doing this. Sympathy is a feeling that conveys the same micropolitical capacity (Clark 1997), and it is present in some parts of the narratives, as in this passage from Vânia's speech:

When it happens you're shocked, you feel pity here and there, but not enough to affect me.

You feel pity towards these chaps who burgled you? What do you feel towards them? Well, when it happens, you're outraged, right? My husband kept saying: "I want to remember their faces well, if one day they get out, and they show up at the hospital, I'll say: "Sort these blokes out!". I mean he, but me too; when it happens, I also think I say it. When it happens that's how I stay. I really have pity, because they are poor fools, they are… people who don't have… I think that they don't have love. They are lacking a total love. So it's people that have nothing. And they don't even have anything to lose, not even life, because they are really risking themselves and they don't fear anything (Vânia).

Ursula's statement explicitly introduces a further feeling that is veiled in the other narratives: impotence, to which the interviewee makes reference at various moments. Her statement establishes various relationships between impotence, fear, rage and pity:

Look, one was very tall, right? And he spoke -the one that I went to the closet with, who was threatening us the whole time, the one with the guns, whose bullets fell and he kept looking for them -and he was brown-skinned, you know? Tall. He told me he was on parole, that he was robbing to eat, you see? That he had a four month old daughter and that he had no money, that he had tried to get a job but when they knew he was a former convict they had sent him away, that he was stealing to eat. The other… […] No, this one I felt pity, we feel pity right?

The one who was with me in the hall, in the closet… And when he left, he started making many threats… He kept looking at me like this: "You'll see! And this and that…". You know? Those things. Then you get scared, because… you feel like this, it is pity mixed with fear, you see? It's like impotence, because you see him, he came in, what is he going to do there?

Now, when it happened, I wasn't angry, you see? Some people come up to me: "Ah! You weren't angry? Didn't feel like picking up a gun and killing everyone?". I don't do that. I didn't feel that way. I felt much more pity. Even the lieutenant said to me: "I cannot believe you said this, ma'am. Why are you trying to excuse this blackie!". I said: "But I cannot lie before the judge!". I also said: "Look at his mother over there! Tell me that you don't feel pity towards this creature?!" What drove her to this? Because this thing, deep down, if your son follows in bad footsteps, right? If he is an addict or something, or from a rich or a poor class, the fault is always the family's. Because the family didn't know right? Something was missing there, you see? Because it's not possible that a person is born bad.

In the first two fragments, pity stems from fear and from impotence before threats; in the third, pity emerges as an alternative to the rage that can be roused by threats. In these cases, the logic that guides this emotional dynamics is a conception of the causes of the aggressor's behaviour as extrinsic to his conscious decision (to his "nature"). Clark (1997) comments on the existence, in the contemporary United States, of a "sociologization" of the conceptions of the subject's responsibility for his own actions, exempting him from guilt in function of the "macro" level conditionings that constituted him vi . It is this logic that seems to guide Ursula's statement: "guilt" never lies with the subject, but always with the social environment that constitutes him and conforms his actions.

A final statement reinforces the existence of "pity" as a relevant emotional aspect of these experiences of victimization. After we had finished our interview, and the recorder had been turned off, Joana told me that prior to the burglary she had been "anesthetized", without "seeing people". After the burglary, she began to feel "pity" for them.

In her speech, she does not name these people who were invisible and who, upon being noticed, elicit pity. We can only understand who they are through the associations she makes when, as the conversation proceeded, she told me the case of a person whom she met by accident and whom she had not noticed had been a cleaner at her house: "for me, she was merely a detail in my life ". vii The association between violence and poverty, connected to the differences between social classes, with which I began my analysis, here re-emerges in an emotional shade: the "other" that harms is the same "other" that provides her services. Upon noticing this "other" she no longer feels indifference, but rather a pity for her condition, establishing through this pity a hierarchy in which she, the interviewee, occupies the higher status position.

Joana's "pity" thereby seems to carry out the micropolitical task that Clark (1997) attributes to sympathy: the establishment of boundaries between social groups. For Clark, sympathy is an asymmetric feeling that is both made possible through the occupation of socially distinct positions and highlights or reinforces the asymmetry between one who gives compassion and the other who receives it. It is this asymmetric character of sympathy that leads to a reflection on "emotional micropolitics": "Even when sympathizers do not consciously intend it, giving sympathy can have micropolitical consequences. Ironically, a sympathy transaction in the socioemotional economy may bring people closer and at the same time widen the social gap between them." (:228)

The perception of facing an "other" of a different nature is perfectly clear in the words that Ursula attributes to her husband, aimed at a burglar, in an effort to convince him that he had neither guns nor objects of great value: "We are good people, man! We don't have anything here! I've never harmed anyone! I'm a doctor! I treat people just like you!".

People who are, therefore, different from him.

Conclusion

The analysis of the statements has revealed the existence of a set of feelings that are articulated and that form an emotional dynamics capable of performing various "tasks". These experiences of victimization elicit in the interviewees feelings of humiliation, fear and/or impotence, which can flow, at least in theory, through one of three "channels": rage, contempt or sympathy. How are we to explain the recurrence, among the interviewees, of this particular emotional dynamics?

In an analysis of the emotional dynamics that engender so-called "heinous crimes" (a father beats his baby because it does not obey his orders to stop crying, or a man kills his neighbour for obstructing the passageway into his garage), Katz (1988), basing himself on an interactionist perspective, proposes that the attitudes of the victims were interpreted by the aggressors, in that situation, as a challenge to the "moral good" that is essential to how they see themselves, thus causing what is perceived by them as a "righteous slaughter". The baby that will not stop crying challenges parental authority; the neighbour who obstructs the passageway to a garage threatens property rights; or the husband who burns his wife's books and disturbs her studies disrespects women's rights.

In all of these scenes, Katz identifies an emotional dynamics that begins with a "holistic" feeling of humiliation, something which takes hold of the aggressor and which challenges his self-image, seeming to him, at that moment, to be eternal. Rage would follow from the fundamental necessity of upholding this self-image, functioning thus as a "counter-point" to humiliation and motivating an aggression which, on the one hand, does not necessarily seek the aggressor's death (it could be halted by a change of attitude, such as an apology, for instance), but on the other is not fulfilled by it (it can be followed by further aggressions to the victim's corpse). What is at issue here is an emotional complex of humiliation-rage, the logic of which is a defence of a certain morality perceived by the aggressor as essential to his identity.

The emotional dynamics identified in the narratives under analysis can be best understood by being contrasted with that identified by Katz in the universe of his analysis. The empirical expression of rage as a reaction or aggression towards the perpetrator is, in the interviewees' perception of the situation, undesirable insofar as it is capable of placing at risk their physical integrity and/or that of their spouses, relatives, friends and employees. The emotional dynamics described by Katz (1998), in which humiliation is turned into rage, seems to be unavailable to these interviewees.

Yet the aggressions analysed by Katz are not merely actions of an instrumental nature: they are mainly expressive actions through which the aggressors intend to reclaim their self-esteem and re-establish moral values understood to be a supreme good, constitutive of their identity and their view of the world. What is to be done, then, when the definition of the situation seems, in the eyes of the narrator, to bar this course of action?

My hypothesis is that contempt and sympathy appear as feelings capable of realizing, on the emotional level, the same task as physical aggression: in their micropolitical capacity, contempt and sympathy re-establish the hierarchy that is threatened by the invasion of homes, the expropriation of goods, by offenses and threats, and by occasional physical aggression. These feelings, however, do more: articulated to a representation of the burglars as "disorderly" or "ignorant", contempt and sympathy suggest that we are faced with a perception of urban violence that is associated with differences of social class, understood in terms of buying power and/or place of residence. And it is precisely the hierarchy between these two distinct "social classes" (to which the "burglar" and the "victim" would belong), inverted by violence, that these feelings strive to restore.

Humiliation, fear and impotence, alongside rage, contempt and sympathy, make up an emotional complex imbued with a dynamics particular to these situations of victimization, capable of providing us with a guide to understanding subjective experience that is associated with a certain perception of violence. viii This emotional complex accomplishes the subjective task of restoring a hierarchy that, in the view of the interviewees, their condition as victims had shaken, thus making evident a relation between emotional grammars, interpersonal relations and social organization.

This type of analysis of the experience of victimization thus hopes to add to the fundamental theoretical project of which this article is the result: the limits and possibilities of the construction of emotions as an object of analysis for social anthropology, here explored through their micropolitical capacity, in its potential as a means to access the study of noble and canonical themes of the social sciences, such as urban violence.

Notes

i The husbands of these interviewees did not agree to be interviewed. ii I have elsewhere offered a more detailed studies of the history of the anthropology of emotions in North American anthropology (Rezende and Coelho 2010;Coelho and Rezende in press). iii As is usual, all names are fictitious. iv This feature of the narrative structure of reports of victimization also emerge in my statements, as I have mentioned elsewhere (Coelho 2006). v Translator's note: the Baixada Fluminense is a low-lying region in Rio de Janeiro's hinterland, which is the source for much of the low-paid and unqualified labour in Rio de Janeiro. vi The relationship between the conception of the subject's responsibility for misfortune and the emergence of compassion is also present in other analyses of this feeling in other places and times, such as in French's (1994) discussion of the attitudes of refugees in Cambodian camps when faced by those who suffered amputations because of mines. vii Joana's statement powerfully and synthetically illustrates Soares' diagnosis of the "invisibility" that characterizes both sides of the "divided city" (Ventura 1994) that Rio de Janeiro has become: "those 'from below' are frequently invisible to those from above, except when they instill fear, discomfort or come to represent a real or imagined threat" (Soares 2000: 41). viii In other work I have explored different emotional dynamics associated with forms of perceiving violence, such as the humiliation-courage dynamics associated with a conception of violence as abandonment (Coelho 2009a), the rage-calmnessfear triad, articulated with gender (Coelho 2006(Coelho , 2009b and the role of calmness as a discursive strategy for pacifying the subject (Coelho and Santos 2007).

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Open Access An ontology for cell types
2005

Jonathan Bard
Department of Biomedical Sciences
Hugh Robson Building
University of Edinburgh
EH8 9XDEdinburghUK

Seung Y Rhee
Department of Plant Biology
Carnegie Institution of Washington
93405StanfordCAUSA

Michael Ashburner firstname.lastname@example.com
Department of Genetics
University of Cambridge
CB2 3EHCambridgeUK

EMBL-European Bioinformatics Institute
CB10 1SDHinxton, CambridgeUK. Correspondence

Michael Ashburner

Open Access An ontology for cell types
62212005Genome Biology 2005, 6:R21 comment reviews reports deposited research refereed research interactions information Method
An ontology for cell types
We describe an ontology for cell types that covers the prokaryotic, fungal, animal and plant worlds. It includes over 680 cell types. These cell types are classified under several generic categories and are organized as a directed acyclic graph. The ontology is available in the formats adopted by the Open Biological Ontologies umbrella and is designed to be used in the context of model organism genome and other biological databases. The ontology is freely available at http://obo.sourceforge.net/ and can be viewed using standard ontology visu-alization tools such as OBO-Edit and COBrA.
AbstractWe describe an ontology for cell types that covers the prokaryotic, fungal, animal and plant worlds. It includes over 680 cell types. These cell types are classified under several generic categories and are organized as a directed acyclic graph. The ontology is available in the formats adopted by the Open Biological Ontologies umbrella and is designed to be used in the context of model organism genome and other biological databases. The ontology is freely available at http:// obo.sourceforge.net/ and can be viewed using standard ontology visualization tools such as OBO-Edit and COBrA. The electronic version of this article is the complete one and can be found online at http://genomebiology.com/2005/6/2/R21 R21.2 Genome Biology 2005, Volume 6, Issue 2, Article R21 Bard et al. http://genomebiology.com/2005/6/2/R21 Genome Biology 2005, 6:R21 http://genomebiology.com/2005/6/2/R21 Genome Biology 2005, Volume 6, Issue 2, Article R21 Bard et al. R21.3 comment reviews reports refereed research deposited research interactions information Genome Biology 2005, 6:R21 Genome Biology 2005, Volume 6, Issue 2, Article R21 Bard et al. R21.5 comment reviews reports refereed research deposited research interactions information

Background

One of the most challenging problems now facing the model organism databases is the formal description of phenotypic data. While some databases, for example those for mouse (Mus musculus) [1], corn (Zea mays) [2] and fruit fly (Drosophila melanogaster) [3], include a rich heritage of data describing the phenotypes of mutants, and some progress is being made to bring these data into a well structured computable representation [3][4][5], the annotation of these phenotypes is hampered by a lack of structured information describing a variety of other biological objects, including cell types. A structured vocabulary of cell types is also required by databases for the description of other biological objects, such as gene-expression data. In addition, using the same concepts for the description of these data in all of these databases would facilitate interoperability among them.

To address these needs, we have developed an ontology that describes the cell types of the major model organisms, both animal and plant. Its use will allow a biologist to query a single database with such questions as: list all of the cell types in mouse that express the Notch gene and all of the cell types in Drosophila and Caenorhabditis elegans that express the closest homolog of this gene; list all of the genes in mouse, rat, human and zebrafish that are expressed in the cell type Schwann_cell; CL:0000218; list all of the genes in D. melanogaster and C. elegans that have a mutant phenotype in the cell types that develop from the cell type myoblast; CL:0000056. The use of the cell ontology will thereby promote the de facto integration of data from diverse databases.

Since the development of the Gene Ontology (GO) for the annotation of attributes of gene products [6], many ontologies have been developed in the model organism informatics community. Several of these are available, in a choice of common formats, from the Open Biological Ontologies (OBO) site [7]. They include comprehensive developmental and anatomical ontologies for many model organisms (for example, mouse, Drosophila, Arabidopsis thaliana and C. elegans), and ontologies for mouse pathology and human disease.

There are several other ontologies that include cell types such as Systematized Nomenclature of Medicine (SNOMED) [8], the Foundational Model of Anatomy (FMA) [9], the anatomy ontologies used in model organism databases at the OBO site [7], vocabularies used by the resources that hold cell lines such as the American Type Cell Collection (ATCC) or the European Collection of Cell Cultures (ECACC) [10,11], and others [12,13]. Our approach for handling cell types differs from that adopted by these resources. First, SNOMED, FMA and the species-specific anatomy ontologies explicitly assume that the cell types they include are associated with one particular organism. Their identifiers cannot therefore be used to annotate cell types from other organisms, even if these cell types are essentially identical to those in the organism-specific ontologies. Second, these resources, together with those that hold cell lines (for example, ECACC and ATCC), tend to define cell types as constituents of tissues rather than provide phenotypic information about their attributes -the knowledge that they encapsulate is severely limited. Third, some ontologies do not have publicly available identifiers for each term; hence they cannot be used for general annotation [10,11]. The Plant Ontology [14] provides a cell type node that shares some of the organizing principles of our cell ontology, but it is limited to those cell types found in plants. For all these reasons, we set out to produce an organism-independent ontology of cell types based on their properties (such as functional, histological and lineage classes) and report here the availability on the Open Biological Ontologies site [7] of this ontology, which incorporates the cell types possessed by a broad range of phyla and is defined by a rich set of criteria.

Results

The ontology

The first design decision was whether we should attempt to integrate cell types from all phyla within a single ontology or build independent ontologies for different taxonomic groups. The former has the great advantage of facilitating de facto integration of data from diverse databases, as described above. This approach does, however, pose conceptual problems: for example, are a mammalian 'muscle_cell' and a nematode 'muscle_cell' homologous? In this particular example we have little doubt that the answer is 'yes'; both of these cell types are evolutionary descendants of the first metazoan's 'muscle_cell'. In other cases, however, matters are not quite as straightforward, a plant 'hair_cell', a 'hair_cell' of the mammalian cochlea and an insect 'hair_cell' are probably not homologous, despite some similarities in their functions and genes expressed within them [15]. Despite these problems in building an 'integrated' cell-type ontology, the advantages, were we to succeed, outweigh them, and we have therefore taken this approach to develop a single ontology that integrates cell types from different phyla.

The ontology consists of concepts or terms (nodes) that are linked by two types of relationships (edges). This means that the ontology appears as a complex hierarchy (technically known as a directed acyclic graph, or DAG) where a given term (or concept) may not only have several children, but also several parents. The parent and child terms are connected to each other by is_a and develops_from relationships. The former is a subsumption relationship, in which the child term is a more restrictive concept than its parent (thus chondrocyte is_a mesenchyme_cell). The latter is used to code developmental lineage relationships between concepts, for example that a hepatocyte develops_from a mesenchymal_cell. The is_a relationship implies inheritance, so that any properties of the parent concept are inherited by its children; the develops_from concept carries no inheritance implications.

The rules for building the ontology are the same as those defined by the GO Consortium. That is, each concept in the Cell Ontology has an identifier with the syntax CL:nnnnnnn, where nnnnnnn is a unique integer, and CL identifies the Cell Ontology, (concepts should always be cited with their full identifier when being used in the context of a database). In addition, if there are precisely equivalent terms in other databases, for example in the Fungal Anatomy [16], Arabidopsis [17], Plant Ontology [14] or FlyBase databases [3], then the unique identifiers from these databases are included in the Cell Ontology. Most concepts in the Cell Ontology are provided with free-text definitions and may have one or more synonyms. Within the context of this ontology, synonyms are precise; a concept and its synonym can be exchanged without changing the concept's meaning. We use the same stratagem as does the GO when we have concepts that are lexically identical but have different meanings in different communities [18]. Thus, it is far from obvious that vertebrate and invertebrate pigment cells are homologous and these concepts are therefore described as pigment_cell_(sensu_Vertebrata) and pigment_cell_(sensu_Nematoda_and_Protostoma, respectively.

The two top-level nodes of the Cell Ontology are cell_in_vivo and experimentally_modified_cell. The former includes cell types that occur in nature, the latter those that are experimentally derived, including cell lines and such constructs as protoplasts. Experimentally derived cells are under-represented in the current version of the ontology. Naturally occurring cells are classified both by organism-independent categories and by organism (animal cells, plant cells, prokaryotic cells). The organism-independent classification of cells follows several different criteria that include: 'function' (for example, electrically_excitable_cell, secretory_cell, photosynthetic_cell), histology (for example, epthelial_cell, mesenchyme_cell), lineage (for example, ectodermal_cell, endodermal_cell) and ploidy (for example, haploid_cell, polyploid_cell). The present version of the Cell Ontology has an average 'depth' of about 10 nodes.

The richness of the ontology can be illustrated by example (Figure 1). Kupffer cells are specialized vertebrate macrophages of the reticuloendothelial system. They function to filter small foreign particles (including bacteria) and old reticulocytes from the blood. In the Cell Ontology they are to be found by their function (they are a type of defensive_cell), by their lineage (they are derived from a mesodermal_cell derived from a hematopoietic_stem_cell, itself a type of stem_cell), by their morphology (they are a type of circulating_cell) and by their organism (they are a type of animal_cell).

Discussion

Ontologies in bioinformatics are intended to capture and formalize a domain of knowledge, and the ontology reported here attempts to do this within the domain of cell types. It is designed to be useful in the sense that a researcher should be able to find, in a rapid and intuitive way, any cell type in any of the major model organisms and, having found it, learn a considerable amount about that cell type and its relationships to other biological objects.

A core feature of the ontology, and one that differentiates it from other resources that contain cell types such as SNOMED and the FMA [8,9], and the Drosophila and Arabidopsis ontologies [3,17], is that the cell ontology explicitly sets out to include cell types from all the major model organisms within a common framework. In addition, it also seeks to incorporate a great deal of phenotypic information about these cell types and is thus far more comprehensive in its cellular detail than these other resources. The intention is that the new cell-A screenshot of the cell ontology, as seen within the OBO-Edit program, displaying all the information associated with the term hepatocyte Figure 1 A screenshot of the cell ontology, as seen within the OBO-Edit program, displaying all the information associated with the term hepatocyte. The left-hand panel shows all the top-level terms, together with the location of hepatocyte within the cell_by_histology classification. The right-hand panel shows all the hierarchies within which hepatocyte can be found. The top part of the central panel illustrates how the term is found, while the lower part gives the definition, the unique Cell Ontology ID and the MESH ID.

type ontology should provide organism-independent knowledge as well as cell-type unique identifiers (ID) that can be incorporated into any database holding cell-type-associated knowledge. The formalized structure of the ontology, together with its set of unique IDs, will allow curators to incorporate cell-type data into their databases, integrate the data with the knowledge encapsulated in the ontology, and use the IDs to interoperate with other databases. While we expect such bioinformatics applications to be its immediate use, we hope that, in the longer term, all biologists will find the ontology useful.

The expected short-term use of the ontology will thus be in cataloguing phenotypes and gene expression patterns. Indeed, it is quite surprising that those who work with model organisms still lack the bioinformatics resources needed to catalogue, archive and access the details of the phenotypes emerging from mutant screens and natural variations. A robust representation of normal and mutant phenotypes in all of the model organisms will require ontologies for a wide range of macroscopic properties (pathology, anatomy, abnormal quantifiers, and so on) and we view the cell ontology as a component of this programme that should be useful in cataloguing phenotypes (and other attributes) associated with cell types.

In the long term we expect that molecular biology and biological databases will move beyond being gene-centric and that biological mechanisms will be studied at a more integrated level. Cells are the biological units with which tissues and organs and organ systems are built. A rich and explicit description of cell types across phyla that are adapted by biological databases will help facilitate this transition.

Finally, it should be pointed out that, like many such resources, this ontology is not complete: although it contains all the common cell types, there will certainly be some that have been omitted. Most importantly, although many of the cell types are fully described by function, morphology, organism, and so on, others are inadequately described and more relationships need to be made. A particular weakness is the fact that the category identified as experimentally_modified_cell has yet to be populated, and doing this will involve consideration of the various cell lines held in the major collections. As with other community resources, community input is essential for the development and maintenance of the Cell Ontology; biologists with comments and additions are therefore welcome to contribute to the ontology and should contact the curator ashburner @ebi.ac.uk.

Materials and methods

The ontology includes the major cell types from the major model organisms (for example, human, mouse, Drosophila, Caenorhabditis, zebrafish, Dictyostelium discoideum, Arabi-dopsis, fungi and prokaryotes). These cell types have been collated from our own knowledge, from major textbooks (for example [20][21][22]), from the embryo and anatomy ontologies available on the OBO site [7], and from colleagues (who are thanked in the acknowledgements). The ontology currently holds some 680 cell types, together with their synonyms and, in most cases, text definitions.

The ontology was constructed using the open source Java tool OBO-Edit (previously known as DAG-Edit) [23], which is convenient for building ontologies that are consistent with the GO formalism. The resulting ontology is available in both the GO 'flat-file' format [24] and the newly defined 'OBO format' [25], and can easily be viewed using the OBO-Edit or the COBrA open source Java tool [26].

Availability

The Cell Ontology is available from the OBO site [19]. Following the cell.obo link will take the user to a page in which the current version of the Ontology, and archived older versions, can be viewed (view) or downloaded (download). Differences between the current and previous version can be seen by following the Diff to link.
 Acknowledgements J.B. is supported by the BBSRC, M.A. is supported by an MRC Programme Grant to M.A. and S. Russell and by NIH grants for FlyBase and the Gene Ontology Consortium, S.R. is supported in part by NSF grants DBI-9978564 and PGRP-0321666 and NIH grants to the Gene Ontology Consortium and MetaCyc. We are grateful to many colleagues for their help in developing this resource, in particular to David States for information on vertebrate blood cells, David Hall for information about C. elegans, Rex Chisholm for information about Dictyostelium, Monte Westerfield for information about zebrafish and Katica Illic and Leonore Reiser for information about Arabidopsis and flowering plants. We also thank Suzanna Lewis and John Day-Richter for their help.
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