Tuesday, August 22, 2000

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Feed Beyond Alchemy
"THE COMPARISON IS IRRESISTIBLE: The search for the sequence of the human genome, the substance that transmutes a single fertilized cell into bodies of astonishing variety, remarkably resembles the mythical Philosopher's Stone, the object of alchemical fascination that would unlock the secrets of the physical world. Now that the human genome, the object of the biggest Big Science project in the history of biology, has finally been sequenced (more or less), we seem to be on the verge of the biological equivalent of turning lead into gold. By recording the essential instructions for human life, the sequenced genome clearly marks a new scientific era."

"In fact, what the bioinformaticists (scientists who use computers to explore biological information) in San Diego are talking about are the ways in which this neat view of the world -- dominant since Mendel's genetic experiments were rediscovered at the turn of the last century -- is a vast oversimplification.

"These questions will gradually move out of the genetics labs, and as we better understand the network of relations between genes, bodies, and environments, the boundaries between biology and medicine, medicine and psychiatry, psychiatry and sociology, sociology and environmental studies, environmental studies and biology will continue to blur. If the lesson of the Philosopher's Stone has any relevance for the monumental achievement of a sequenced genome, it is the way the search for the Stone marked not the completion of alchemy but its replacement -- by something altogether more rigorous and useful."

Yahoo! News Genomics Research to Be Boosted by New International Data Consortium Launched At Major Biocomputing Meeting
"A multinational group of biotechnology and pharmaceutical companies is being formed to establish common computing standards for data and information analyses related to gene-based drug development. The lack of a single information standard worldwide prevents intelligent linking and sharing of information developed by different companies, public databases and academic institutions, and is considered to be a major obstacle for more rapid development of gene-based pharmaceutical and other products. "

""The design of models for bioprocess representation and simulation are very open,'' said Dr. Neumann. "The Consortium will need to examine and discuss relationships between all pathway information, protein interaction data, and biological and disease processes so that we can generate informatics specifications for any combination of these types of data.''"

The BioPathways Consortium Why the Need for a BioPathways Consortium?
"With the completion of several genomics initiatives, including the Human Genome Project, researchers are poised to begin the next phase of elucidating how living systems function. This involves the identifcation of genes and their functions, followed by their organization according to their roles and interactions within the more global context of cellular mechanisms. Constructing representations of the latter will involve not only structural information, but more dynamic and causal forms relevant to biochemical processes.

To ensure the success of capturing, organizing, and utilizing this information, there is an urgent need to discuss and develop new informatics technologies that will support such new forms of biological information. Data regarding pathways and interactions is already being accumulated in dozens of different formats, but no standard way of representing or exchanging them exists to date. In order to prevent the confusion that has occurred in bioinformatics due to the lack of early standards, we plan to be preemptive in considering specifications while this field is in its early stages. On a more fundamental level, representations of biological processes should provide the foundation for and thus may have an important bearing on the definition(s) of biological function."

redux [07.25.00]
The Scientist The Language of Bioinformatics
[requires 'free' registration]
"Once the world had a single language and not too many words, but then clarity deteriorated into clamor. Today in the small but prolific world of bioinformatics, another Tower of Babel is rising up, with the miscommunication due as much to the rapid expansion of information as to basic changes in how it is processed. "Horrible problems" crop up as more information is computed on instead of read by a human researcher, according to Ewan Birney, a group leader in the Ensembl genome annotation project at the European Bioinformatics Institute (EBI) in Cambridge, England.

In the early days of bioinformatics, human-readable data exchange formats such as ASN.1, the format adopted for GenBank by the National Center for Biotechnology Information (NCBI) 10 years ago, were the norm. Easily editable with a text utility, ASN.1's syntactic looseness makes it congenial to the human user, but not to the machine, which likes its inputs defined with dictatorial rigidity."

redux [05.10.00]
The XML Cover Pages XML and Semantic Transparency
"We may rehearse this fundamental axiom of descriptive markup in terms of a classical SGML polemic: the doubly-delimited information objects in an SGML/XML document are described by markup in a meaningful, self-documenting way through the use of names which are carefully selected by domain experts for element type names, attribute names, and attribute values. This is true of XML in 1998, was true of SGML in 1986, and was true of Brian Reid's Scribe system in 1976. However, of itself, descriptive markup proves to be of limited relevance as a mechanism to enable information interchange at the level of the machine.

As enchanting as it is to contemplate the apparent 'semantic' clarity, flexibility, and extensibility of XML vis-à-vis HTML (e.g., how wonderfully perspicuous XML <bookTitle> seems when compared to HTML <i>), we must reckon with the cold fact that XML does not of itself enable blind interchange or information reuse. XML may help humans predict what information might lie "between the tags" in the case of <trunk> </trunk>, but XML can only help. For an XML processor, <trunk> and <i> and <booktitle> are all equally (and totally) meaningless. Yes, meaningless.

Just like its parent metalanguage (SGML), XML has no formal mechanism to support the declaration of semantic integrity constraints, and XML processors have no means of validating object semantics even if these are declared informally in an XML DTD. XML processors will have no inherent understanding of document object semantics because XML (meta-)markup languages have no predefined application-level processing semantics. XML thus formally governs syntax only - not semantics."

redux [05.01.00]
Stanford Medical Informatics Preprint Archive Ontology-Oriented Design and Programming
"In the construction of both conventional software and intelligent systems, developers continue to seek higher level abstractions that both can aid in conceptual modeling and can assist in implementation and maintenance. In recent years, the artificial intelligence community has placed considerable attention on the notion of explicit ontologies -- shared conceptualizations of application areas that define the salient concepts and relationships among concepts. Such ontologies, when joined with well defined problem-solving methods, provide convenient formalisms for modeling and for implementing solutions to application tasks. This chapter reviews the motivation for seeking such high-level abstractions, and summarizes recent successes in building systems from reusable domain ontologies and problem-solving methods. As the environment for software execution moves from individual workstations to the Internet at large, casting new software applications in terms of these high-level abstractions may make complex systems both easier to build and easier to maintain. "

Gene Ontology Consortium
"This is the home of the Gene Ontology Consortium. The goal of the Gene Ontology consortium is to produce a dynamic controlled vocabulary that can be applied to all eukaryotes even as knowledge of gene and protein roles in cells is accumulating and changing."

"The three organising principles of GO are molecular function, biological process and cellular component. A gene product has one or more molecular functions and is used in one or more biological processes; it may be, or may be associated with, one or more cellular components."

redux [03.30.00]
JAMIA Integration and Beyond: Linking Information from Disparate Sources and into Workflow
"The vision of integrating information—from a variety of sources, into the way people work, to improve decisions and process—is one of the cornerstones of biomedical informatics. Thoughts on how this vision might be realized have evolved as improvements in information and communication technologies, together with discoveries in biomedical informatics, and have changed the art of the possible. This review identified three distinct generations of "integration" projects. First-generation projects create a database and use it for multiple purposes. Second-generation projects integrate by bringing information from various sources together through enterprise information architecture. Third-generation projects inter-relate disparate but accessible information sources to provide the appearance of integration. The review suggests that the ideas developed in the earlier generations have not been supplanted by ideas from subsequent generations. Instead, the ideas represent a continuum of progress along the three dimensions of workflow, structure, and extraction. "

JAMIA Integration and Beyond: Panel Discussion
"I think one of the toughest things we all have to deal with is updating our dictionaries. In the simplest cases, the name of an organism is changed and we just have to do the maintenance. It is tougher, when, as with Citrobacter, they do genetic studies and say, "Oh, it's really six different organisms, not one." We have the human genome project coming very quickly. Even that is just the tip of the iceberg. We're not only going to see all the genes; we're then going to see clinical tests based on gene expression. Essentially, you'll be able to look at something on the order of 180,000 gene products and whether they're up or down regulated. How are we going to integrate such an incredible amount of data at a time when we're going to also be changing how we think about these processes? Classification and simple mapping are not going to work, because the lumpers and splitters are going to be arguing furiously on a daily basis."

redux [07.11.00]
Biospace.Com Big Picture Biology
"For most of us, formal biology education begins with complex systems--the traditional dissection of a frog in high school biology class is virtually a rite of passage in the U.S.

But the way many people learn about and invest in biotechnology is at the smallest end of the spectrum--the genome, now often described as the "periodic table" of biology. Genomics and all its related buzzwords have been responsible for much of the media attention, government grants, and investment capital heaped on the biotech industry over the past decade.

But just as there is a whole lot of chemistry that happens in between the periodic table and a birthday cake, there is a lot of biology in between the genome and a living organism. With the completion of biology's periodic table within sight, academics and industry players alike are pondering the best way to apply our hard won knowledge.

The only problem is, the path from genome to system seems to get harder the more we learn."