Online research in philosophy

The theme of the third annual Spring workshop of the HUPO-PSI was proteomics and beyond and its underlying goal was to reach beyond the boundaries of the proteomics community to interact with groups working on the similar issues of developing interchange standards and minimal reporting requirements. Significant developments in many of the HUPO-PSI XML interchange formats, minimal reporting requirements and accompanying controlled vocabularies were reported, with many of these now feeding into the broader efforts of the Functional Genomics (...) Experiment (FuGE) data model and Functional Genomics Ontology (FuGO) ontologies. (shrink)

Systems biology is largely tributary to genomics and other “omic” disciplines that generate vast amounts of structural data. “Omics”, however, lack a theoretical framework that would allow using these data sets as such (rather than just tiny bits that are extracted by advanced data-mining techniques) to build explanatory models that help understand physiological processes. Systems biology provides such a framework by adding a dynamic dimension to merely structural “omics”. It makes use of bottom-up and top-down models. The former are based (...) on data about systems components, the latter on systems-level data. We trace back both modeling strategies (which are often used to delineate two branches of the field) to the modeling of metabolic and signaling pathways in the bottom-up case, and to biological cybernetics and systems theory in the top-down case. We then argue that three roots of systems biology must be discerned to account adequately for the structure of the field: pathway modeling, biological cybernetics, and “omics”. We regard systems biology as merging modeling strategies (supplemented by new mathematical procedures) from data-poor fields with data supply from a field that is quite deficient in explanatory modeling. After characterizing the structure of the field, we address some epistemological and ontological issues regarding concepts on which the top-down approach relies and that seem to us to require clarification. This includes the consequences of identifying modules in large networks without relying on functional considerations, the question of the “holism” of systems biology, and the epistemic value of the “systeome” project that aspires to become the cutting edge of the field. (shrink)

Everyone in biology keeps predicting that the next few years will bring answers to some of the major open questions in evolutionary biology, but there seems to be disagreement on what, exactly, those questions are. Enthusiasts of the various “-omics” (genomics, proteomics, transcriptomics, metabolomics, and even phenomics) believe, as Michael Lynch puts it in the final chapter of The Origins of Genome Architecture, that “we can be confident of two things: the basic theoretical machinery for understanding the evolutionary process (...) is well established, and we will soon be effectively unlimited by the availability of information at the DNA level.”. (shrink)

Individualized care and equality of care remain two imperatives for formulating any scientifically and morally informed public health policy. Yet both continue to be elusive goals, even in the age of genomics, proteomics, and evidence-based medicine. Nonetheless, with the rapid growth and improvement of human biotechnologies, the need to individualize therapies while allocating medical care equally may result partly from our biological constitution. Human beings are all unique, and their biological differences significantly influence variability in disease causation and therapeutic (...) response to treatments. However, because humans have equal moral worth, there is no ethically justifiable reason to establish an a .. (shrink)

Biomedical ontologies are emerging as critical tools in genomic and proteomic research where complex data in disparate resources need to be integrated. A number of ontologies exist that describe the properties that can be attributed to proteins; for example, protein functions are described by Gene Ontology, while human diseases are described by Disease Ontology. There is, however, a gap in the current set of ontologies—one that describes the protein entities themselves and their relationships. We have designed a PRotein Ontology (PRO) (...) to facilitate protein annotation and to guide new experiments. The components of PRO extend from the classification of proteins on the basis of evolutionary relationships to the representation of the multiple protein forms of a gene (products generated by genetic variation, alternative splicing, proteolytic cleavage, and other post-translational modification). PRO will allow the specification of relationships between PRO, GO and other OBO Foundry ontologies. Here we describe the initial development of PRO, illustrated using human proteins from the TGF-beta signaling pathway (http://pir.georgetown.edu/pro). (shrink)

New concepts may prove necessary to profit from the avalanche of sequence data on the genome, transcriptome, proteome and interactome and to relate this information to cell physiology. Here, we focus on the concept of large activity-based structures, or hyperstructures, in which a variety of types of molecules are brought together to perform a function. We review the evidence for the existence of hyperstructures responsible for the initiation of DNA replication, the sequestration of newly replicated origins of replication, cell division (...) and for metabolism. The processes responsible for hyperstructure formation include changes in enzyme affinities due to metabolite-induction, lipid-protein affinities, elevated local concentrations of proteins and their binding sites on DNA and RNA, and transertion. Experimental techniques exist that can be used to study hyperstructures and we review some of the ones less familiar to biologists. Finally, we speculate on how a variety of in silico approaches involving cellular automata and multi-agent systems could be combined to develop new concepts in the form of an Integrated cell (I-cell) which would undergo selection for growth and survival in a world of artificial microbiology. (shrink)

This paper follows the circuitous path of theories concerning the origins of viruses from the early years of the twentieth century until the present, considering RNA viruses in particular. I focus on three periods during which new understandings of the nature of viruses guided the construction and reconstruction of origin hypotheses. During the first part of the twentieth century, viruses were mostly viewed from within the framework of bacteriology and the discussion of origin centered on the “degenerative” or the “retrograde (...) evolution theory.” However, concomitantly, in the context of origin-of-life theorizing, the notion that viruses are vestiges of a prebiotic world was also being contemplated. In the 1960s the idea that viruses were genetic elements that “escaped” from cells became prevalent. These traditional hypotheses are being revisited nowadays by evolutionary virologists, who have placed them within a new conceptual framework that is supported by cutting-edge genomic and proteomic data. Two current, opposing scenarios of virus origin are presented. The philosophical dimensions of “revisiting” the original hypotheses are briefly discussed. (shrink)