The governments of China, India, and the United Kingdom are unanimous in their belief that bioinformatics should supply the link between basic life sciences research and its translation into health benefits for the population and the economy. Yet at the same time, as ambitious states vying for position in the future global bioeconomy they differ considerably in the strategies adopted in pursuit of this goal. At the heart of these differences lies the interaction between epistemic change within the scientific (...) community itself and the apparatus of the state. Drawing on desk-based research and thirty-two interviews with scientists and policy makers in the three countries, this article analyzes the politics that shape this interaction. From this analysis emerges an understanding of the variable capacities of different kinds of states and political systems to work with science in harnessing the potential of new epistemic territories in global life sciences innovation. (shrink)

"Databases containing the accumulated genomic data of the research community are growing exponentially. This book contains cutting-edge insights from scholars, bioethicists and legal practitioners who work at the ever-changing intersection of law and bioinformatics"--Page 4 of cover.

This article deals with the integration of ethical reflection into the research practices of the project at the Lille Nord-Pas-de-Calais genopole: “Multifactorial genetic pathologies and therapeutic innovations”. The general hypothesis of this text is that changes in research practices in biology (mainly through the use of bioinformatics) imply changes in medical practices, which require critical reflection. This hypothesis could be broken down into three sub-hypotheses: (1) Research in biology is undergoing a complete transformation; (2) Research in biology is a (...) cultural practice, which cannot be reduced to a simple cognitive action; (3) Research in biology is a techno-scientific practice. As for the method, the aim of our research at the Medical Ethics Centre is to elucidate the philosophical and ethical range of biomedical practices. This work entails a double task for reflection. On the one hand, from the revelation of ethical tensions present in these practices, we have to think about what is at stake in these practices, and more broadly in society. On the other hand, we have to analyse the conditions enabling the actors to assume the significance of ethical reflection in their practices. The method set up to undertake this double task could be qualified as “narrative hermeneutics”, as its aim is to attempt to interpret the stakes in practices from proximity with these practices and from what their actors have to say about them. The text then goes on to analyse more specifically the emergence and place of bioinformatics in present-day biomedical research. (shrink)

Reading, writing, publishing, and publicly presenting scientific works are vital for a young researcher's profile building and career development. Generally, the traditional educational curricula do not offer training possibilities to learn and practice how to prepare, write, and present scientific works. These are rather a part of lab meeting activities in research groups. The lack of such training is more critical in some developing countries because this adds to the rare opportunities to discuss and become involved in the exchanges on (...) state of the art scientific literature. Here the authors relate their experience in introducing a weekly 1‐day lab meeting in the framework of two previously organized 3‐month courses on “Bioinformatics and Genome Analyses”. The main activities which are developed during these lab meetings include scientific literature follow up as well as preparing and presenting oral and written scientific reviews. These activities prove to be useful for a student's self‐confidence building, for enhancing their active participation during the lectures and practical sessions, as well as for the positive impact on running the whole course program. Incorporation of such lab meeting activities in the course program significantly improves the capacity building of the participants, their analytical and critical reading of scientific literature, as well as communication skills. In this work it is shown how to proceed with the different steps involved in the implementation of lab meeting activities, and to recommend their regular institution in similar courses. (shrink)

In the life sciences, where large data sets are increasingly setting the stage for research, the role of bioinformatics is expanding. This has far-reaching consequences, not only for the way research is done, but also for the way this research affects our understanding of human identity. Using two case studies of practices involving bioinformatics, the software program Structure and the Genome of the Netherlands project, I will argue that bioinformatics and its tools can be understood as ‘infrastructure’ (...) as described by Bowker and Star. A number of value decisions are involved in the development of such tools. However, once the tools are ready for use, these values tend to blend into the background of the research. This may lead to the ‘naturalisation’ and ‘essentialisation’ of value-imbued aspects of population identities such as nationality, ethnicity and race. (shrink)

There is a need recognized by the National Institute of Dental & Craniofacial Research and the National Cancer Institute to advance basic, translational and clinical saliva research. The goal of the Salivaomics Knowledge Base (SKB) is to create a data management system and web resource constructed to support human salivaomics research. To maximize the utility of the SKB for retrieval, integration and analysis of data, we have developed the Saliva Ontology and SDxMart. This article reviews the informatics advances in saliva (...) diagnostics made possible by the Saliva Ontology and SDxMart. (shrink)

Motivation: One approach to inferring genetic regulatory structure from microarray measurements of mRNA transcript hybridization is to estimate the associations of gene expression levels measured in repeated samples. The associations may be estimated by correlation coefficients or by conditional frequencies or by some other statistic. Although these procedures have been successfully applied to other areas, their validity when applied to microarray measurements has yet to be tested. Results: This paper describes an elementary statistical difficulty for all such procedures, no matter (...) whether based on Bayesian updating, conditional independence testing, or other machine learning procedures such as simulated annealing or neural net pruning. The difficulty obtains if a number of cells from a common population are aggregated in a measurement of expression levels. Although there are special cases where the conditional associations are preserved under aggregation, in general inference of genetic regulatory structure based on conditional association is unwarranted. Contact: tchu@ andrew.cmu.edu. (shrink)

It is probable that, increasingly, genome investigations are going to be based on statistical formalization. This review summarizes the state of art and potentiality of using statistics in microbial genome analysis. First, I focus on recent advances in functional genomics, such as finding genes and operons, identifying gene conversion events, detecting DNA replication origins and analysing regulatory sites. Then I describe how to use phylogenetic methods in genome analysis and methods for genome‐wide scanning for positively selected amino acids. I conclude (...) with speculations on the future course of genome statistical modeling. BioEssays 25:266–273, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

What is life and what does it mean to be in the living political universe of entitiness without rhyme or reason? Flappy exudate, a bag in a bag, corpuscles of corporeality, worms (or flesh tubes) with appendages, even the cult of first involution – these are our body pods and the hunger and thirst of being-in. How can the situation of anatomical form be analysed without the illusion of instrumentalized reflection? Perhaps by amalgamating the categories and their issues. The issuance (...) of taxonomy is the actual fine muck of excrement, which every brick of ordered life leaks as exudence and decay. Deep thoughts leave a mucal snail trail of what was tabular-seeming about our bodily situation, our environs, our friends, our experiments and our nourishment. Especially in this current age of 露 露 and 娜娜 (Lulu and Nana), our first officially public transgenic kindred, the question becomes, ‘who are these free-living divergences and what does it mean to be the uber-ding beyond geoengineering’s capabilities?’. (shrink)

ABSTRACT In this paper I analyse the ethical implications of the two main competing methodologies in genomic research. I do not aim to provide another contribution from the mainstream legal and public policy perspective; rather I offer a novel approach in which I analyse and describe the patent‐and‐publish regime (the proprietary regime) led by biologist J. Craig Venter and the ‘open‐source’ methodologies led by biotechnology Nobel laureate John Sulston. The ‘open‐source methodologies’ arose in biotechnology as an alternative to the patent‐and‐publish (...) regime in the wake of the explosion in computer technology. Indeed, the tremendous increase in computer technology has generated a corresponding increase in the pace of genomics research. I conclude this paper by arguing that while the patent‐and‐publish method is a transactional method based on the exchange of extrinsic goods (patents in exchange for research funds), the free and open‐source methodology (FLOSS)1 is a transformational method based on a visionary ideal of science, which leads to prioritizing intrinsic goods in scientific research over extrinsic goods. (shrink)

The automatic integration of information resources in the life sciences is one of the most challenging goals facing biomedical informatics today. Controlled vocabularies have played an important role in realizing this goal, by making it possible to draw together information from heterogeneous sources secure in the knowledge that the same terms will also represent the same entities on all occasions of use. One of the most impressive achievements in this regard is the Gene Ontology (GO), which is rapidly acquiring the (...) status of a de facto standard in the field of gene and gene product annotations, and whose methodology has been much intimated in attempts to develop controlled vocabularies for shared use in different domains of biology. The GO Consortium has recognized, however, that its controlled vocabulary as currently constituted is marked by several problematic features - features which are characteristic of much recent work in bioinformatics and which are destined to raise increasingly serious obstacles to the automatic integration of biomedical information in the future. Here, we survey some of these problematic features, focusing especially on issues of compositionality and syntactic regimentation. (shrink)

Bioinformatics – the so-called shotgun marriage between biology and computer science – is an interdiscipline. Despite interdisciplinarity being seen as a virtue, for having the capacity to solve complex problems and foster innovation, it has the potential to place projects and people in anomalous categories. For example, valorised ‘outputs’ in academia are often defined and rewarded by discipline. Bioinformatics, as an interdisciplinary bricolage, incorporates experts from various disciplinary cultures with their own distinct ways of working. Perceived problems of (...) interdisciplinarity include difficulties of making explicit knowledge that is practical, theoretical, or cognitive. But successful interdisciplinary research also depends on an understanding of disciplinary cultures and value systems, often only tacitly understood by members of the communities in question. In bioinformatics, the ‘parent’ disciplines have different value systems; for example, what is considered worthwhile research by computer scientists can be thought of as trivial by biologists, and vice versa. This paper concentrates on the problems of reward and recognition described by scientists working in academic bioinformatics in the United Kingdom. We highlight problems that are a consequence of its cross-cultural make-up, recognising that the mismatches in knowledge in this borderland take place not just at the level of the practical, theoretical, or epistemological, but also at the cultural level too. The trend in big, interdisciplinary science is towards multiple authors on a single paper; in bioinformatics this has created hybrid or fractional scientists who find they are being positioned not just in-between established disciplines but also in-between as middle authors or, worse still, left off papers altogether. (shrink)

Two senses of ‘ontology’ can be distinguished in the current literature. First is the sense favored by information scientists, who view ontologies as software implementations designed to capture in some formal way the consensus conceptualization shared by those working on information systems or databases in a given domain. [Gruber 1993] Second is the sense favored by philosophers, who regard ontologies as theories of different types of entities (objects, processes, relations, functions) [Smith 2003]. Where information systems ontologists seek to maximize reasoning (...) efficiency even at the price of simplifications on the side of representation, philosophical ontologists argue that representational adequacy can bring benefits for the stability and resistance to error of an ontological framework and also for its extendibility in the future. In bioinformatics, however, a third sense of ‘ontology’ has established itself, above all as a result of the successes of the Gene Ontology (hereafter: GO), which is a tool for the representation and processing of information about gene products and their biological functions [Gene Ontology Consortium 2000]. We show how Basic Formal Ontology (BFO) has established itself as an overarching ontology drawing on all three of the strands distinguished above, and describe applications of BFO especially in the treatment of biological granularity. (shrink)

Ruby and Perl are programming languages used in many fields. In this paper we would like to present their usefulness with regard to basic bioinformatic problems. We concentrate on a comparison of widely used Perl and relatively rarely used Ruby to show that Ruby can be a very efficient tool in bioinformatics. Both Perl and Ruby have a built-in regular expressions engine, which is essential in solving many problems in bioinformatics. We present some selected examples: printing the file (...) content, removing comments from a FASTA file, using hashes, printing nucleotides included in a sequence, searching for a specific nucleotide in sequence and translating nucleotide sequences into protein sequences obtained in GenBank format. It is our belief that Ruby’s popularity will rise because of its simple syntax and the richness of its methods. Programs in Ruby are very easy to read and therefore easier to maintain and debug, which are the most important characteristics for a programming language. (shrink)

Recent work on the quality assurance of the Gene Ontology (GO, Gene Ontology Consortium 2004) from the perspective of both linguistic and ontological organization has made it clear that GO lacks the kind of formalism needed to support logic-based reasoning. At the same time it is no less clear that GO has proven itself to be an excellent terminological resource that can serve to combine together a variety of biomedical database and information systems. Given the strengths of GO, it is (...) worth investigating whether, by overcoming some of its weaknesses from the point of view of formal-ontological principles, we might not be able to enhance a version of GO which can come even closer to serving the needs of the various communities of biomedical researchers and practitioners. It is accepted that clinical and bioinformatics need to find common ground if the results of data-intensive biomedical research are to be harvested to the full. It is also widely accepted that no single method will be sufficient to create the needed common framework. We believe that the principles-based approach to life-science data integration and knowledge representation must be one of the methods applied. Indeed in dealing with the ontological representation of carcinomas, and specifically of colon carcinomas, we have established that, had GO (and related biomedical ontologies) followed some of the basic formal-ontological principles we have identified (Smith et al. 2004, Ceusters et al. 2004), then the effort required to navigate successfully between clinical and bioinformatics systems would have been reduced. We point here to the sources of ontologically-related errors in GO, and also provide arguments as to why and how such errors need to be resolved. (shrink)

An ontology is a domain of knowledge structured through formal rules so that it can be interpreted and used by computers. Ontologies are becoming increasingly important in bioinformatics because they can be linked to the information in databases and their knowledge then used to query the databases. Typical examples in current use are the Gene Ontology, which incorporates much of our knowledge about gene products, and ontologies of developmental anatomy, which, for example, facilitate tissue‐based queries to gene expression databases (...) both textually and spatially. This article considers the production, formulation and types of bio‐ontologies together with the reasons why they are so useful. © BioEssays 25:501–506, 2003. © 2003 Wiley Periodicals, Inc. (shrink)

Serial analysis of gene expression (SAGE) is a powerful technique that can be used for global analysis of gene expression. Its chief advantage over other methods is that it does not require prior knowledge of the genes of interest and provides qualitative and quantitative data of potentially every transcribed sequence in a particular cell or tissue type. This is a technique of expression profiling, which permits simultaneous, comparative and quantitative analysis of gene‐specific, 9‐ to 13‐basepair sequences. These short sequences, called (...) SAGE tags, are linked together for efficient sequencing. The sequencing data are then analyzed to identify each gene expressed in the cell and the levels at which each gene is expressed. The main benefit of SAGE includes the digital output and the identification of novel genes. In this review, we present an outline of the method, various bioinformatics methods for data analysis and general applications of this important technology. BioEssays 26:916–922, 2004. © 2004 Wiley Periodicals, Inc. (shrink)

There are a number of existing classifications and staging schemes for carcinomas, one of the most frequently used being the TNM classification. Such classifications represent classes of entities which exist at various anatomical levels of granularity. We argue that in order to apply such representations to the Electronic Health Records one needs sound ontologies which take into consideration the diversity of the domains which are involved in clinical bioinformatics. Here we outline a formal theory for addressing these issues in (...) a way that the ontologies can be used to support inferences relating to entities which exist at different anatomical levels of granularity. Our case study is the colon carcinoma, one of the most common carcinomas prevalent within the European population. (shrink)

A quiet revolution in genetics is increasingly rendering our milieu strange and artificial. Epigenomics, informatic cousin of epigenetics, is a xenoforming process, giving birth to an alien milieu, replacing the natural with the technical. If epigenetics is understood as the heritable changes in gene expression that do not alter DNA sequence, epigenomics takes as object the set of epigenetic modifications. Environmental, social, even political aspects of life’s variability are re-understood digitally in epigenomic profiles, the previous categories computationally accounted for as (...) potential triggers of epigenesis. Following Gilbert Simondon, the xenoforming procedures of epigenomics can be understood as the concretization and adaptation processes of a technical object, the invention of which gives birth to a technogeographic milieu. In this article, the author examines Simondon’s work, especially, ‘On the Mode of Existence of Technical Objects’, alongside contemporary scholarship on epigenetics. (shrink)

The intersection of ethics, computing, and genetics plots a space not yet adequately mapped, despite its importance, indeed, its rapidly growing importance. Its subdomains are well-enough known: or the study of ethical issues in genetics and genomics, is part of core curricula everywhere. Ethics and computing is an established subfield. Computing and geneticshas in little more than a decade progressed from subsubspecialty to the sine qua non of contemporary biomedical research, and it bids fair to transform clinical practice. We must (...) prepare for the complete digitization of the genomes of individual patients and the storage of millions of these genomes in very large databases. (shrink)

This paper is the result of the research I undertook at Lancaster University with a Marie Curie Fellowship during the academic years 2000‐2002. The objective of this research was to study the limits and the challenges of the analogy between molecular geneticists’ work and hackers’ activities. By focusing on this analogy I aim to explore the different ethical and philosophical issues surrounding new genetics and its IPR regulations. The paper firstly will show the philosophical background lying behind the proposed analogy (...) and analyses the sense in which we can talk of geneticists as “hackers.” It will provide grounds for the analogy by exploring some of the techniques used by geneticists; in particular it will focus on the so‐called Shotgun method for genomic sequencing. After having provided reasons for the proposed analogy I will claim that the open source philosophy used in the computer field would be a good way to regulate research in the genetics and in pharmaceutical field too. The open source philosophy would provide fair distribution of research opportunities around the globe with the shift from patenting to copyright in sensitive fields such as genetics. (shrink)

Ontological principles are needed in order to bridge the gap between medical and biological information in a robust and computable fashion. This is essential in order to draw inferences across the levels of granularity which span medicine and biology, an example of which include the understanding of the roles of tumor markers in the development and progress of carcinoma. Such information integration is also important for the integration of genomics information with the information contained in the electronic patient records in (...) such a way that real time conclusions can be drawn. In this paper we describe a large multi-granular datasource built by using ontological principles and focusing on the case of colon carcinoma. (shrink)

This report describes the rationale, approaches, organization, and resource development leading to a large-scale deletion bin map of the hexaploid wheat genome. Accompanying reports in this issue detail results from chromosome bin-mapping of expressed sequence tags representing genes onto the seven homoeologous chromosome groups and a global analysis of the entire mapped wheat EST data set. Among the resources developed were the first extensive public wheat EST collection. Described are protocols for sequencing, sequence processing, EST nomenclature, and the assembly of (...) ESTs into contigs. These contigs plus singletons were used for selection of distinct sequence motif unigenes. Selected ESTs were rearrayed, validated by 5′ and 3′ sequencing, and amplified for probing a series of wheat aneuploid and deletion stocks. Images and data for all Southern hybridizations were deposited in databases and were used by the coordinators for each of the seven homoeologous chromosome groups to validate the mapping results. Results from this project have established the foundation for future developments in wheat genomics. (shrink)