{bio,medical} informatics
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GenomeWeb
Proteomics Effort Shouldn't Mimic Genome Project, Experts Say"Can sequencing do for the proteome what it did for the genome?
On Wednesday, a number of world-renowned researchers in the field of proteomics issued a resounding " no."
Instead of devoting their efforts to decoding the human proteome, proteomics researchers should focus on developing a larger picture of protein structure, function, and pathways within cells and organisms, panelists said at a New York Academy of Sciences briefing entitled "The Promise of Proteomics."
"When a company has phenomenal success with strategy A, you want to do strategy A on the next subject," said John Richards, a professor of organic and biochemistry at California Institute of Technology, referring to current corporate attempts to map the proteome.
"This doesn't work," he said."
redux [07.11.00]
"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."
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Nature: Science Update
Protein predictors need start to finish"Figuring out the shape of the proteins encoded by the thousands of genes in every cell may have just got a little easier. Researchers in Switzerland have made a discovery which they say "pushes the simulation of protein folding processes within reach"1. It is all about knowing where to start."
"An unfolded or 'denatured' protein is not compacted into a well-organized shape. It is more like a loosely tangled ball floating in water. Attempts to model protein folding by computer often assumed that it doesn't matter much what denatured state you start with, since they are all more or less equally messy.
Not so, says van Gunsteren's team..."
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The Independent
The secret of life? It's free on the Web"The internet is usually seen as an online library, a place to surf the hours away and do your virtual shopping, not as the medium to pass around the world ground-breaking research that could help save mankind.
It hasn't quite happened yet, but just outside Cambridge there is a group of scientists who are quietly using the web to disseminate material about genes that should lead to greater knowledge about how human beings work, and why some of us develop diseases.
In a biological version of the Microsoft versus Linux battle over charging or making operating- system source code freely available, the Human Genome Project is challenging gene patentees by posting its research on the internet."
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BioMedNet
Ethicists outwitted as insurers demand too much genetic data too fast[requires 'free' registration]
"The genetic test for Huntington's disease should never have been approved for use by insurance companies in the UK, one of Britain's leading experts on medical genetics told parliamentary investigators yesterday evening. The condemnation of government policy comes as BioMedNet News can reveal that insurers have outwitted ethics watchdogs by requiring more genetic information from clients than they are entitled to demand.
Genetic tests are being given a "predictive weight that the scientific evidence does not yet support," said Martin Bobrow, head of the Department of Medical Genetics at the Wellcome Trust for Molecular Mechanisms in Disease in Cambridge."
redux [10.31.00]
"Space has been called the last frontier. But now modern science has begun exploration of another new territory: the human genome. In mapping this instruction book of life, researchers are becoming able to pinpoint genes for a wide array of diseases and to guide creation of revolutionary new drug treatments.
But this new age of discovery also is resurrecting old issues of privacy and discrimination. Medicine can now accurately predict who will contract certain illnesses, such as Huntington's disease, but it still cannot save patients from its debilitating effects. On the other hand, a woman might test positive for a gene predisposing her to breast cancer but nevertheless live a long, cancer-free life.
How can medical records be protected so patients are free to be tested for genetic defects without losing health insurance or being unfairly eliminated on job applications? Those who work with medical records--whether electronic or paper-based--will undoubtedly come face-to- face with such privacy considerations very soon, if they haven't already."
redux [05.15.00]
[requires 'free' registration]
"Lawrence Berkeley National Laboratory in California has settled a class-action suit over genetic and medical testing for more than $2 million. The suit was brought by employees who charged that they were discriminated against and that their privacy was invaded when they were tested for pregnancy, syphilis, and genetic traits without their knowledge. Each of the plaintiffs will get $25,000, and other employees may get $2,000 each. The settlement also covers legal fees estimated at $440,000.Reference: Lehrman, S. 2000. Medical tests cost Lawrence Berkeley $2.2 million. Nature 405(6783):110."
redux [07.18.00]
"Privacy advocates, still reeling from last year's passage of legislation that allows banks and insurance companies to share personal information, are bracing against a new threat to the confidentiality of medical and financial information: The Human Genome Project.
"Latanya Sweeney, professor of computer science and public policy at Carnegie Mellon University, said currently more than 40 US states have laws requiring hospitals to make available to insurance companies and researchers certain information about each visit they receive, including the diagnosis, birth date, ethnicity, gender and Zip code of all patients discharged.
While state regulations say such categories are sufficiently anonymous to conceal the identity of patients, Sweeney said companies can and do match such information with personally identifiable data, using just a few publicly available resources."
""It may surprise some to know that 87 percent of the US population is uniquely identifiable today by just their birthday, gender and zip code," Sweeney said."
"Sweeney said the stakes become much higher when genetic information comes into play. For instance, she said, gender can usually be identified using just the base of a person's DNA sequence. Using a larger chunk of DNA information, researchers can infer particular diseases by catalogued and known sequence patterns. Link those sequences to publicly available hospital data, and you have an undeniably complete picture of an individual's most private information, Sweeney said."
redux [06.08.00]
"Unless they begin preparing now, health plan executives and medical directors could be blindsided by the revolution in medicine that will come with the mapping of the human genome, members of a managed care conference keynote panel warned on Monday."
"You think the genetic revolution is still 3-to-5 years off for your health plans," said Dr. Billings, who also serves as deputy director and chief medical officer of the Heart of Texas Veterans Health Care System. "I have to tell you, you better wake up. The tsunami is on the horizon," he warned.
For example, Schering-Plough's Dr. Haverty predicted that gene-based information could lead to the identification of many different types of asthma. As a result, health plans will need to develop many new codes and to upgrade their information systems, he said."
redux [03.30.00]
"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."
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BioMedNet
Over 1500 life scientists pledge to use only journals that archive for free[requires 'free' registration]
"A grass-roots movement is gaining momentum among life scientists, who are pressing for the creation of a permanent, public Internet archive of life science research, provided free of charge. The "Public Library of Science" inititative, begun last November by Stanford University biochemist Patrick Brown, has picked up the support of some 1,600 scientists to date."
redux [11.13.00]
"A group of leading American scientists is promising to boycott scientific journals that refuse to make research articles available free of charge. The scientists have joined a campaign to promote the unfettered exchange of scientific information and establish a web-based public library for science."
"The supporters of the initiative believe that it will "vastly increase the accessibility and utility of the scientific literature, enhance scientific productivity, and catalyze integration of the disparate communities of knowledge and ideas in biomedical sciences." Campaigners aim to prevent the published record of scientific research, much of it paid for with public funds amounting to tens of billions of dollars a year, from being "permanently controlled and monopolized by publishers."redux [11.03.00]
"publiclibraryofscience.org was established to promote the unfettered exchange of scientific information and to organize community support for an international online public library of science. We are asking all scientists of all nations to sign the following letter, which we plan to publish as an open letter in May 2001. Your support will help us to persuade the publishers of scientific journals to commit to giving their archival material to the public domain for distribution through online public libraries. More information about this effort, and a list of journals that are currently compliant is available in our FAQ. Click here if you would like to sign the open letter. We welcome your questions and comments at feedback@publiclibraryofscience.org.
This website is intended to provide information about the open letter and the "public library" initiative to interested scientists, and to provide a convenient mechanism for scientists to sign the letter. Because the open letter is not intended to be "published" until May 2001, we ask that neither the letter nor the list of scientists who have signed the letter be reported elsewhere before May 2001."
[requires 'free' registration]
"Research librarians will meet with the US Justice Department next week to discuss their concerns over publishing monopolies and increasing costs. They've asked the US government to block the merger of two of the largest scientific publishing companies in the world."
"Elsevier owns about 300 biomedical journals and Harcourt owns about 200 biomedical titles. Combining the two publishing houses will give Elsevier 33 to 45% of the market share within biomedical publishing, he says. There's no hard and fast threshold to determine anti-trust monopolies, but this number is clearly above the line, McCabe says."
redux [10.19.00]
""Publishers are reluctant to give away content because they are concerned that advertisers may go away," said Jerome Kassirer, former editor-in-chief of the New England Journal of Medicine. "Advertisers pay more attention to the number of subscriptions to paper journals than to the number of eyeballs on any given website."
"There's a lot of anxiety that if (print journals) have an electronic offering, people will migrate online and they will lose their paper subscription revenues," agreed Tony Delamothe, editor of BMJ Online, a medical association journal that, unlike most journals, does not charge to access its electronic content.
Some insist that simply publishing electronically is not enough --and that open, free access is necessary to disseminate global research."
redux [09.20.00]
"How should biomedical research be communicated? How should research be assessed and validated?"
"Below are abstracts, transcripts, and biographies from the conference. Some presentations did not lend themselves to transcription. Where possible we have supplemented them with editorials from the speakers.
We have also commissioned editorial articles from several speakers and delagates at the meeting.
All thoughts, comments, and suggestions are welcome on our email discussion list"
"What if you could wave a wand, in this very Harry Potter decade, and make libraries - at least digital libraries - more open, more easy to manage, cheaper, and even more eclectic and democratic? What if content contributors could submit, catalog, index, manage, rate and rank materials in large collections themselves? I believe that, thanks to the innovations from the Open Source community and perhaps more importantly the Free Software community, that we can have a contributor-run library at this very moment.
In fact, there are several very successful examples from which we can draw not only best practices, but also - that grail of the programmer - working code. But better still, these projects are also examples of vibrant, lively, noisy, democratic communities. "
"Librarians are increasingly called upon not only to collect information in electronic form but also to organize it into digital libraries. The materials may be created and held locally, or they may be created and accessed in a distributed fashion as a virtual library. Digital libraries can provide material on a variety of topics, from children's games to high-energy physics. Their scope may be local, national, or even international; the audience may be a small group with specialized interests or the broader public. Essential to the successful implementation and use of any digital library is the organization of that library, either directly or indirectly, by one or more knowledge organization systems (KOS).
The term knowledge organization systems is intended to encompass all types of schemes for organizing information and promoting knowledge management. Knowledge organization systems include classification and categorization schemes that organize materials at a general level, subject headings that provide more detailed access, and authority files that control variant versions of key information such as geographic names and personal names. Knowledge organization systems also include highly structured vocabularies, such as thesauri, and less traditional schemes, such as semantic networks and ontologies. Because knowledge organization systems are mechanisms for organizing information, they are at the heart of every library, museum, and archive. "
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Nature: Science Update
Burger bug genome revealed"Researchers tackling the killer bacterium Escherichia coli O157:H7 now have something meaty to chew on — the bug's full genome sequence."
"An unusual feature of the newly unravelled genome sequence is the presence of 'DNA islands'. These are sections of DNA unique to E. coli O157:H7 and are scattered throughout its genome. Other DNA islands are found only in the benign laboratory strain."
""The sheer magnitude of the differences was totally shocking to us," says lead author Nicole Perna, an assistant professor of animal health and biomedical sciences. "We couldn't just zoom in on areas of difference between the two species. The changes were scattered throughout."
The two strains of E. coli share about 3,500 common genes. But the O157:H7 strain had 1,300 additional genes that were not found in the harmless strain. The benign "cousin" bacteria also had 530 unique genes that were not shared with O157:H7.
"This is a very 'plastic' genome, it changes quite rapidly," Perna says. "What this tells us is over a relatively short time on an evolutionary time scale, on the order of five million years, you get tremendous variation in the DNA of two similar organisms.""
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The Scientist
Academia or Industry?[requires 'free' registration]
"Maria Betty, a bioinformatics specialist for a major pharmaceutical company based in New Jersey, received her Ph.D. in molecular biology, worked as a postdoc for two years and moved into bioinformatics about four years ago. She went straight into industry from her Ph.D. The low salaries, along with the constant pressure to write papers and obtain grants was a sufficient deterrent to academic life, with the greater industry salaries offering the primary reason for heading in that direction.
"I saw my colleagues slaving night and day, earning meager salaries for essentially the same type of job as better paid industry-based scientists," she recalls."
redux [09.19.00]
"If job searching were a poker game, Alan Williams would be sitting pretty with a full house.
Fresh out of graduate school, he happens to have a rare combination of skills that drives employers to offer hefty salaries, stock options and bonuses. And it's not even a dot-com job.
Williams has a combination of computer programming and molecular biology know- how. His job is to use computers to mine the vast store of data in the human genome model."
redux [09.01.00]
[requires paid registration]
"Since Next Wave last covered bioinformatics, in our July 1996 Profiles of Bioinformaticians and February 1997 Bioinformatics Skills features, the prominence of the bioinformatician's role in modern biology has only increased. This month, Next Wave provides a comprehensive picture of the current state of bioinformatics, from the funding situation in Europe and the U.S. to the new bioinformatics degree programs and the immediate hiring needs of industrial and academic labs around the world.”
redux [07.25.00]
"Are you a hacker? Do you yearn for something more important to work on than yet-another-gnome-applet? Are you annoyed that you can't find a problem that is fun to code and stretches your brain in new ways... bioinformatics might be the answer."
"The amount of data is growing faster than anyone expected and only a handful of people can both remain with academic ideals and coding potential. We need hackers to join any number of projects out there. And there are a host to join. If you just liking hacking perl or you prefer compiler technology, there is something to suit you. "
redux [06.27.00]
"A fast-growing field known as bioinformatics uses computing to analyze the vast amount of biological, genomic, and related research to make sense of things too complex for the human brain to fathom.
But bioinformatics is also a bottleneck for many drug and biotech companies that can't find enough talented software engineers who combine sophisticated analysis tools with an understanding of genomics.
''We resolve the bioinformatics issue [by hiring] two people: one who understands computer science and the biologist or researcher,'' said Kenneth Fasman, vice president and global head of informatics of AstraZeneca LLC in Waltham."
"...according to Dr. Donald Johnson, a pathologist at the Nebraska University Medical Center. He estimated there are about 60,000 jobs available to scientists and managers versed in bioinformatics."
redux [05.10.00]
"As expected, salaries for the most part climb as the level of training rises, starting in the $40,000-$50,000 range for BAs and reaching over $100,000 for one post doc. But there are exceptions. For example, two of the three undergraduates who were placed received salaries between $50,0000 to $60,000. This is higher than that earned by seven of the masters students, although ten of the nineteen masters students for whom we have salary information earn more than $60,000. One masters student received a starting salary of over $100,000. Reported salaries for five hires at the doctorate level are over $70,000. One is between $80,000 to $90,000; another is over $100,000; yet another is between $60,000 to $70,000. Three post docs received placements with a salary between $80,000 to $90,000. One post doc was placed at a salary of over $100,000. One institution reported that one or more masters student(s) received a signing bonus.""The results of our current survey make it clear that the majority of these jobs are not being filled by graduates of formal programs—who by our count represent about 15 percent of the positions advertised in 1997. And, we believe the 15 percent figure to be an overestimate given that ads have been growing over time and our most recent ad count is for 1997, a year earlier than our hiring data. This leads us to infer that most of the advertised positions are being filled by individuals trained in informal programs and by individuals who change jobs. The distinct possibility exists that a number of these jobs remain vacant for a period of time, an issue not studied here. Furthermore, our pipeline estimates (see Table 2) lead us to conclude that the number of individuals currently enrolled in formal programs falls far short of the number of positions that have recently been advertised."
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Laboratory Network
New platform for integrating heterogeneous bioinformatic tools"The National Center for Genome Resources (NCGR; Santa Fe, NM) has released a version of ISYS, a new platform to integrate heterogeneous bioinformatics software tools and databases. The software can be easily downloaded and installed from the NCGR website and offers most of the functionality planned for the full users' release later this spring."
"The ISYS platform achieves integration not by integrating the data per se, but by integrating the applications that retrieve, display, and analyze the data. This, the develops say, is based on their observation that it is the experts themselves—those in gene expression research, gene ontology classifications, sequence alignment algorithms, etc.—who know best how to put their data in context. Putting data into context is an important step in transforming mere information into knowledge."
"Integrating heterogeneous bioinformatics resources is difficult because the field is decentralized and moving rapidly. Many developers do not perceive an incentive to adhere to nascent standards sufficient to outweigh the cost of constrained development. Agreeing on standards is time-consuming and difficult (some even suggest futile). In the absence of global standards, most groups are trying to achieve integration by building their own "enterprise-wide" integrated systems from scratch, with web-based solutions that rely on networks of hypertext links, or with cross-database query systems that rely on complicated schema-mapping techniques . Each of these approaches has significant disadvantages. Large-scale, de novo development is slow and expensive, and can result in systems that are extinct before they are completed. Web-based solutions are severely limited by the user-interface capabilities of web browsers, and are ineffective for integrating local data with remote data. Cross-database query solutions make an unnecessary separation between data integration and software integration, and sometimes over-emphasize the importance of complex declarative queries..."
"We believe that ISYS represents a fundamentally different approach to the problem."
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The New York Times
Human Genome Project Director Peers Into the Future[requires 'free' registration]
"The director of the federal government's Human Genome Project is predicting that "a number of big surprises'' will come out of genetics research in the coming weeks.
Speaking at a National Institutes of Health conference on ethical and social issues in genetics, Dr. Francis Collins said that a "spate of papers in public journals'' due out within a month will signify the incredibly rapid pace of scientific discovery seen since the announcement of the nearly complete sequencing of the human genome last summer.
The first, Collins said, will be a paper that puts the total count of human genes at between 30,000 and 35,000. ''That's less than half the number most people have been predicting.'' The second is a study ascribing previously unknown biological missions to genes scientists thought were inactive, or so-called "junk genes.''
"There is now clear evidence that (the junk genes) have been performing a number of functions for tens or hundreds of thousands of years,'' he said."
redux [11.13.00]
[requires 'free' registration]
"If James Watson, co-discoverer of DNA's structure, says we don't know how many genes there are, you're inclined to believe him. So it was a great surprise to hear the legend denounced, albeit with due deference. At the last count, insisted Kay Davies, professor of anatomy at the University of Oxford, humans are reckoned to have 40,944 tiny protein factories.
She was drawing on statistics that define the proteome, the protein equivalent of the genome, as the set of all expressed proteins in humans, for which 40,944 genes are individually responsible. Not a huge figure, she noted, barely the equivalent of three flies or a couple of worms. "Apologies Jim, let's talk over tea," she added."
redux [05.13.00]
"Well, they weren't all men, but mostly. The betting in the pub continued, the lowest bet being 29,800 genes placed by Pat Tome and the highest number coming from John Quackenbush at 118,259.The pool was organized by Erwin Birney, a team leader at the European Bioinformatics Institute. He tried to convince the bartender to oversee the betting, but was told in no uncertain terms that no gambling was allowed in the Cold Spring bar.
Guesses on the number of genes in the human genome have lowered considerably since the mapping of chromosome 21, which researchers found to contain only 225 genes, far fewer than previously predicted. The researchers on the chromosome 21 study predicted their results could mean that there are as few as 40,000 genes in the entire human genome.
"Someone from Incyte will probably show up and bet 150,000," one gambler said."
redux [11.22.00]
[requires 'free' registration]
"Nearly 97% of the DNA in the human genome is believed to be junk DNA. It may seem wasteful, but most of the DNA in all higher organisms appears to be junk. Whatever information is contained in junk DNA is never translated into proteins. Intron DNA is transcribed into RNA but does not appear after maturation, and it is never translated into protein. To determine if much of the junk DNA is intron DNA, researchers used a new approach to analyze all of the complete or nearly complete genomes on record. They conclude that most junk DNA in animals is intron DNA. Their conclusion, however, does not apply to plant DNA.
Reference: Wong, G.K.-S., Passey, D.A., Huang, Y.-z. et al. 2000. Is "junk" DNA mostly intron DNA? Genome Res. 10(11):1672-1678."
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MSNBC
Genome hunters, Compaq to hook up"Genome hunters at the U.S. Department of Energy and Celera Corp. announced a marriage of computer technology and biology on Friday, saying they will mine the human gene map for information they hope will transform medicine."
"“We in the nuclear weapons industry thought for years that nothing could be more complex than nuclear physics,” Sandia’s Robinson said. He said it was clear that modeling the 250,000 interacting proteins in the human body is far more complex.
Sandia and Celera will write new computer software and the algorithms, the mathematical formulas, that are used to analyze the dense maze of genetic code."
"Sandia's scientists will gain experience applying their expertise in computer science, mathematics and statistics to problems in biology, which promise to be among the most daunting big science undertakings of the new century. "This is the most challenging and the most exciting problem that I've ever been exposed to," said Bill Camp, director of strategic computing at Sandia.
Celera and Sandia will continue to own any patented or copyrighted work they bring to the collaboration, and they will jointly own any newly developed software. The new software may find its way into Celera's commercial products and might also be made available for use by federal laboratories or federally funded scientists in academic labs.
The computer programs written by Sandia and Celera will serve, for Compaq, as models of the kinds of problems supercomputers will need to tackle in the next few years. Out of the effort, Compaq expects to produce an ultra-fast computer that would eventually be sold commercially. Because biological problems closely resemble some other types of computing problems, including those confronted by cryptologists trying to intercept and read enemy communications, the new machine might be of interest to military planners and spy agencies."
"However, the system will be a long time in coming. Bill Blake, vice president of high-performance technical computing at Compaq, said the three partners hope to have a prototype machine ready by 2004. That system is expected to deliver performance ranging between 100 and 150 trillion floating point operations per second, Blake said.
The prototype supercomputer will likely use 10,000 to 20,000 of Compaq's Alpha processors and is being budgeted at $150 million in current costs, according to Blake. He added that the first system could eventually lead to the development of a so-called "petacruncher" -- a machine capable of 1,000 teraflops -- by the end of the decade."
redux [12.18.00]
"The 7.5-teraflop computing cluster that IBM is building for Atlanta-based NuTec Sciences will give IBM a “distinct advantage” in the genomics marketplace, an IBM spokesperson said Monday"
"Some market watchers speculated that IBM, whose computers are historically among the more expensive, might have cut NuTec a deal in order to secure a stronger foothold in the genomics sector.
IBM software for web application serving, information portals, and data integration will also be included in the system. NuTec Sciences will use the system to manage, mine and integrate genetic data from a wide variety of sources, and share this information via the Internet with the global life sciences community."
NuTec plans to run several massively parallel applications on the cluster. Morrissey said that a combinatorics algorithm that NuTec is developing in collaboration with the NIH to analyze disease-causing gene combinations is particularly compute-intensive. This algorithm is running as a test set on the company’s IBM computer in Houston, but Morrissey said they’re awaiting delivery of the supercomputer before it can be scaled up to optimal efficiency."
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The New York Times
When Gene Sequencing Becomes a Fact of Life[requires 'free' registration]
"The gene-sequencing machines that unraveled the human genome were nearly the size of refrigerators and cost $300,000 apiece. Richard T. Daly's sequencers fit easily on a desk — and he is giving them away.
The reason is that Mr. Daly wants to move gene sequencing from research laboratories into daily medical practice. The company he heads, Visible Genetics, has developed a test to sequence genes of the virus that causes AIDS, providing information to help doctors choose which of the 15 or so available drugs will work best against a particular patient's infection.
"You've got a huge medicine cabinet to pick from and no good way to pick," said Mr. Daly, whose company is publicly traded and based in Toronto."
"The use of genetic information to tailor drugs to patients is usually seen as a future promise. But in the battle against AIDS, several companies say that day is here now, and they are racing to build businesses."
redux [07.06.00]
[requires 'free' registration]
"New treatments have extended the lives of AIDS patients and offered hope for a cure, but multidrug-resistant strains can still foil therapy. Researchers used analysis and computer simulations to show that resistance-related treatment failure in patients who consistently take their prescribed drugs is likely due to mutant strains present at the beginning of treatment rather than strains developing during the course of treatment as a result of residual viral replication. The finding stresses the importance of combining drugs with different resistance profiles in order to wipe out all existing drug-resistant strains of the virus early in treatment."
Reference: Ribeiro, R.M. and Bonhoeffer, S. 2000. Production of resistant HIV mutants during antiretroviral therapy. Proc. Natl. Acad. Sci. U.S.A. 97(14):7681-7686."redux [04.05.00]
"HIV drug therapy often fails because of the appearance of multidrug-resistant virus. There are two possible scenarios for the outgrowth of multidrug-resistant virus in response to therapy. Resistant virus may preexist at low frequencies in drug-naïve patients and is rapidly selected in the presence of drugs. Alternatively, resistant virus is absent at the start of therapy but is generated by residual viral replication during therapy. Currently available experimental methods are generally too insensitive to distinguish between these two scenarios. Here we use deterministic and stochastic models to investigate the origin of multidrug resistance. We quantify the probabilities that resistant mutants preexist, and that resistant mutants are generated during therapy. The models suggest that under a wide range of conditions, treatment failure is most likely caused by the preexistence of resistant mutants."
[requires 'free' registration]
"I suspect that although the new enthusiasm for computers in biology is genuine, it overlooks some basic problems in implementation. The basic difficulty, as I see it, is that although biologists use computers, they do not trust everything that comes out of them. It is one thing to use them to print up nice-looking graphs, but it is an entirely different matter to use them to think better."
"Francis Crick was once quoted as saying that no biologist had ever made a discovery using a mathematical model. I would reply that no biologist has ever made a discovery by running an electrophoretic gel. They make discoveries by using their brains. Computers, like all scientific tools, are only as good as the person who uses them. If biologists don't understand how computer models are constructed, they won't know their strengths and limitations. Without some foundation of trust, biologists will be unlikely to utilize or accept this powerful method of data analysis."
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Washington Post
InforMax to Sell Biological Data Software"The deal is with Biomax Informatics AG of Martinsried, Germany. It covers software called the BioRS Integration and Retrieval System, one of several programs that try to make sense of the tsunami of biological data emerging from the world's laboratories."
""The dominant thing we hear from our customers . . . is that it's too much data," said Steve Lincoln, vice president for life sciences at InforMax. "People are overwhelmed. They have a hard time finding the needle in the haystack. People know, to be somewhat glib about it, that somewhere in these databases is the cure for cancer if they could only find it."
"Lion Bioscience said Wednesday it has licensed its SRS database integration platform to TheScientificWorld for use on its website."
"“Researchers will be able to use SRS to search multiple types of databases simultaneously including full text, bibliographic, datasets, and annotated images in a fast and integrated manner," Eric Tomlinson, CEO of TheScientificWorld, said in a statement."
redux [09.14.00]
"IBM is pushing hard against the boundaries of data processing and integration in a way that ultimately could affect everyone's health and well-being.
Through a technology license with Incyte Genomics Inc., IBM is applying its DiscoveryLink technology to the challenge of sifting mountains of genetic data to better identify the causes of diseases and aid in developing cures. DiscoveryLink's data- integration technology will be integrated with Incyte's Genomic Knowledge Platform."
"IBM says it has earmarked $100 million to develop advanced research technology for biotechnology, genomic, E-health, pharmaceutical, and agri-science industries."
"According to new findings by Silico Research (London), the market for bioinformatic platform software and services is currently worth $52 million a year and is growing by 17%. Data volumes, increased confidence in the technology, and the evolution of bioinformatic tools combine to drive market growth. The market is expected to reach $110 million by 2004.
The new research was issued as part of Silico’s e-R&D Insights Program. Companies competing in the bioinformatic platform sector include: Applied Biosciences, Compugen, Genomica, Genome Informatics, IBM, Informax, LION Bioscience, and NetGenics."
"personal bibliography on query mediation, database integration, database interoperability and related topics, concentrating on projects in genomic research. "
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The Boston Globe
Wilson rattles historians with 'bio-history' theories "History is no longer just the study of war and peace, of politicians and economics. If the next generation of historians hopes to understand the driving forces of humanity, they need to know the principles of ecology, population genetics and even molecular biology.
That was the message that Harvard University professor E.O. Wilson, a two-time Pulitzer Prize winner and one of America's leading intellectuals, delivered to a somewhat skeptical audience of the nation's historians, gathered recently in one of the mirrored ballrooms of the Sheraton hotel in Boston. One cannot know history, Wilson said, without knowing how human nature was shaped by hundreds of thousands of years of ''deep history.''"
redux [10.10.00]
[requires 'free' registration]
"Dr. Paul R. Ehrlich, a professor of biology and population studies at Stanford University, believes in evolution — or, more precisely, in evolutions. He believes in Darwinian evolution, of course, and the premise that life evolves through genetic mutations coupled with the crucible of natural selection.
But more important, he believes in the power of cultural evolution — all the nongenetic changes that human societies and individuals undergo, from decade to decade and moment to moment, including changes in language, technology, ethics, behavior, alliances, enmities, schemes and visions."
"A main theme of the book was to emphasize the gigantic role that cultural evolution plays in making individuals different, and in making groups different. I'm hoping to counter a view that I'm afraid is all too common among the American public, that all of our behavior is controlled by our genes, and that there are genes that code for aggressiveness, acquisitiveness and so on.
The truth is, You can never remove culture from the mix."
redux [08.31.00]
""Like any large construction project in the public domain, sequencing the human genome has been a subject of discussion and controversy. Major issues have been the cost of the project, its scientific merit, and the effects of the knowledge gained on human affairs. The concern about cost subsided as the project proved viable and attracted private funding. That leaves the other two questions: What will we learn from this sequence, and how will it affect our lives? With fame and fortune to be made in the genome business, one can only be skeptical of the wondrous claims made by the project's protagonists. The Triple Helix examines these questions from a critical and biologically informed angle."
"In Lewontin's triple helix, the genes are placed in their natural context, where history and geography shape the nature of organisms and the genes they contain. His differences with the most modern of molecular and cellular biologists are irreconcilable and reflect the ever-widening gulf between biologists who have an affinity for what goes on outside the laboratory and those for whom the differences between individuals and between species represent "an annoyance [to be] ignored whenever possible." In many laboratories, organisms are now studied under conditions in which genetic variation is eliminated and the environment held constant. It is only under these special conditions, where neither variation nor natural selection is tolerated, that the triple helix collapses into the double helix and genes appear to be paramount.""redux [08.10.00]
"The 'implication' that seems to worry people most of all is so-called 'genetic determinism'. It's the notion that, if human nature was shaped by evolution, then it's fixed and so we're simply stuck with it — there's nothing we can do about it. We can never change the world to be the way we want, we can never institute fairer societies; policy-making and politics are pointless.
Now, that's a complete misunderstanding. It doesn't distinguish between human nature — our evolved psychology — and the behavior that results from it. Certainly, human nature is fixed. It's universal and unchanging — common to every baby that's born, down through the history of our species. But human behavior — which is generated by that nature — is endlessly variable and diverse. After all, fixed rules can give rise to an inexhaustible range of outcomes. Natural selection equipped us with the fixed rules — the rules that constitute our human nature. And it designed those rules to generate behavior that's sensitive to the environment. So, the answer to 'genetic determinism' is simple. If you want to change behavior, just change the environment. And, of course, to know which changes would be appropriate and effective, you have to know those Darwinian rules. You need only to understand human nature, not to change it."
"In the late 1970s I attended meetings at which sociobiologists E. O. Wilson and David Barash, critic Stephen J. Gould, and others were on a panel. Standing blocked by the crowd in the hall outside the doorway to the packed hall I was unable hear the speakers. I spied a little door near the stage, and figured that if I could get to that door, I could get next to the stage and the front row. I sneaked through the hotel kitchen and found the door. Just as I opened it I was passed by a number of African American students who ran up on stage and poured water on Wilson's head. Wilson responded by saying to the audience that he felt like he had been speared by an aborigine. The crowd applauded the martyred Wilson (on crutches at the time--from a skiing accident) and some in the front row muttered epithets at the disrupters and at me, who appeared to have held the door for the demonstrators. The water pitcher story has been repeated scores of times in journalistic accounts, but none of these mention Wilson's racially tinged response. Two decades later the debate concerning the genetic determination of human behavior has been reanimated in the general intellectual and middle-brow media with a somewhat more restrained tone. The study of evolutionary accounts of human behavior is now called "evolutionary psychology" to avoid some of the justifiably bad connotations that were associated with sociobiology. During the last few years the linguist Steve Pinker, (1997) philosopher Daniel Dennett, (1995) New Republic editor and science popularizer Robert Wright,(1994) and science writer Matt Ridley (1994, 1997) have produced feisty, polemical expositions of evolutionary psychology for a broad audience. Stephen J. Gould has returned to the breach to criticize evolutionary psychology, but several writers considered to be on the left have defended sociobiological approaches and criticized postmodern rejection of biologism.
The core theories of evolutionary psychology are the same as those of sociobiology. Several of the commonly made distinctions between evolutionary psychology and sociobiology turn out not to distinguish the two. So what has changed and what is new?"
"US researchers believe they have identified the parts of the human genome involved in developing a person's intelligence.
This means scientists could soon test the potential intelligence of new-born babies."
"The researchers, working for the US National Institutes of Health, analysed the DNA of 200 of the brightest kids in America and compared them with the genetic material from ordinary children.
The results are due out next year, but the BBC Newsnight programme has learned that key differences have been found. In other words, the scientists are homing in on the genes for genius."
redux [07.07.00]
"Kaplan examines the roles genetic explanations for these types of differences play in our culture -- and how science has been used inappropriately to "medicalize" problems that should be more properly addressed as complex social issues.
Kaplan explores six specific areas -- intelligence (IQ), criminality and violence, homosexuality, depression, obesity, and the centrality of genetics in defining parenthood."
"He also explains the problems involved in "finding genes" for complex human behaviors by comparing the genomes of people who have a particular trait with the genomes of those who do not. The resulting medicalization centers the problem on the individual."
"... an emphasis on the biochemical and the genetic share the property that they make the condition out to be internal to the patient. Once a genetic explanation is offered, and any plausible sounding pathway proposed, the opportunities for claiming that there are other ways of approaching the problem are radically curtailed."
The problem becomes entirely that of personal biochemistry: the danger is in adopting easy solutions without looking at other reasons for the problem -- and without questioning the framework in which certain temperaments or sexual orientations become defined as problems."
redux [05.28.00]
"Suddenly, I'm picturing a new conclusion to "Casablanca," in which Rick walks up to the teary-faced Ilsa as she's about to board the plane with her husband and says: "I was gonna tell you that the problems of three little people don't amount to a hill of beans in this crazy world. But then I saw your BRCA-1 code. Baby, you're staring at the c-stuff. Let's just stay here and party to the bitter end."
"In the Brave New World ahead, are we (and the characters who reflect us) going to run dry of choice? Are we doomed to a movie-viewing future of genetically savvy detectives who catch their man armed with a genetoscope? I mean, what if Jack Nicholson were to turn his back on Faye Dunaway in "Chinatown" because, well, he'd already checked out that family incest history at the GenBank file at the National Institutes of Health."
redux [04.25.00]
"In the current issue of Advances in Complex Systems (February-April), Dr. Yaneer Bar-Yam, president of the New England Complex Systems Institute and an expert on the application of mathematical analysis to complex systems, contends that the selfish-gene theory of evolution is fatally flawed.
If his mathematical proof gains general acceptance, it will shut the door on controversial "gene-centered" views of evolution.
Bar-Yam, in the upcoming article, proves that the "selfish gene" approach is not valid in the general case. He demonstrates that the gene-centered view, expressed in mathematical form, is only an approximation of the dynamics actually at work."
"The key to Bar-Yam's analysis lies in recognizing three levels of structure in nature: the gene, the organism and the group (or network) of organisms."
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EurekAlert
Computer scientist solves old salesman problem"It was a combination of things, physical and metaphysical, that killed Arthur Miller's traveling salesman Willie Loman.
Now a computer scientist at Washington University in St. Louis has developed and tested an algorithm that might at least have made Loman's road traveled a little easier.
Weixiong Zhang, Ph. D., associate professor of computer science at Washington University, has developed an algorithm that attacks an old problem in the computing and business worlds known as the Traveling Salesman Problem (TSP). An algorithm is the backbone of computer operations; it is a step-wise mathematical formula, similar to a recipe, that solves a problem or reaches an otherwise desired end. The Traveling Salesman Problem is actually an umbrella term for a whole host of planning and scheduling problems, often involving routes; a classic one being a postman's route, for instance."
"Zhang also is working on efficient search algorithms for analyzing biological data such as DNA, RNA and protein sequences. He is particularly interested in applying his skills in computer science and artificial intelligence to a relatively new but very active area called computational biology, or bioinformatics."
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Feed
Living Language"EVERYTHING'S COMING up roses! Or more precisely, Arabidopsis thaliana, a somewhat nondescript white flower selected by biologists as the model in the plant kingdom for genetic research. Related to broccoli and cauliflower, A. thaliana is the most studied plant in human history; every week new papers are published about its properties. In an astounding leap forward, the journal Nature just announced that the entire genome for A. thaliana has been sequenced -- a first for the vegetal world. As plants go, it was a relatively easy task; the complete genome runs to 120 megabytes of information, compared to 1.6 gigabytes for wheat and a hefty 3 gigabytes for humanity. What makes this discovery just a bit different from the ever-increasing flow of genetic revelations is that, in another first, Nature has announced that all genomic information presented in its pages -- and on its Web site -- will be published in GEML, or Gene Expression Markup Language, a lingua franca defining a common standard for the bits of life."
redux [12.22.00]
"While the Nature Publishing Group has joined Rosetta Inpharmatics's Gene Expression Markup Language Community, the journal " is not taking sides or picking any standard over another," a Nature spokesman said Friday."
"This clarification of Nature's role in the GEML community came in response to Rosetta's recent public relations campaign, which claimed the journal " officially endorses" the GEML standard.
The announcement prompted the Microarray Gene Expression Database Group to send a letter to the journal stating that the Microarray Markup Language, which the MGED supports, has wider support in academia and industry."
redux [12.12.00]
"The Internet uses HTML, and soon perhaps genomics will use GEML.
At least that's what Rosetta Inpharmatics (RSTA), the creators of Genetic Expression Markup Language, or GEML, is hoping. The prestigious science journal Nature adopted the language on Monday, which should give a significant boost to its acceptance in the scientific community."
"According to Metcalfe's law, penned by 3Com founder Robert Metcalfe, the more people who use any system, the more valuable it becomes. And since researchers will now be required to submit papers using GEML, the value of the language should increase exponentially."
redux [10.30.00]
"Version 1.0 of Rosetta Inpharmatics’ Gene Expression Markup Language (GEML) Conductor tools is now available for downloading from the company website (http://www.rii.com.). This suite of applications, which employs an open-standard XML file format, enables researchers to visualize and exchange data between different gene expression databases and analysis systems.
The company refers to its GEML Conductor tool as a universal solution for visualizing and exchanging gene expression information produced by different technology platforms. It allows users to convert any well-formatted gene expression data file into a common, flexible data format.
Rosetta GEML Conductor tools' features include:
"The inability to analyze gene expression data from multiple technology platforms has long been hampered by software compatibility issues," stated Mark Boguski, senior vice president of research and development for Rosetta Inpharmatics. "By translating diverse data formats into a single common format, the Rosetta GEML Conductor tools enable users to share and visualize information across platforms, thus maximizing the value of gene expression data."
- File Conversion. Users can convert any gene expression data file, including Affymetrix GeneChip and BioDiscovery AutoGen, into the GEML format.
- Plot Viewer. Users can visualize and share data by turning any GEML profile into a plot. The Plot Viewer includes a Zoom feature, which allows magnification into or out of particular sections of a plot.
- Magic Lasso. Users can select specific plot areas for closer viewing.
- Intensity Plot Viewer. Users can measure the intensity of one channel of data against the intensity of another channel of data.
- Customizable Visualization. Users can customize groups, colors, and labels according to viewer preferences.
- InstaLink. Users can access built-in hotlinks to popular databases and information centers on the World Wide Web.
- Table Viewer. Users can convert GEML data into customizable tables with resizable and reorderable columns.
redux [09.15.00]
"This data standard is designed to separate data reporting and collection from methodology used. The profile_type attribute enables keeping track, in the data file, of which methodology was used, enabling normalization across methodologies and thus comparison of data which was collected by a variety of methodologies.
Expression analysis data is generated by a variety of sources and is usually stored in the form of disk files. Industry-wide standards for the formats of such files do not exist, so there are now many different formats, with different representations of data and different types of information stored. For example, some data file formats for chip scans reference a specific pattern, while others do not. Similarly, some data file formats for chip scans can contain the raw image data or can reference one or more image files, while others cannot.
"GEML is a free, public-domain, open-standard XML DTD. GEML was created and is licensed in order to define a single, distinct GEML format and avoid proliferation of incompatible variations.
You may freely use, publish, and redistribute the GEML DTDs, subject to the restrictions in these Terms of Use; write and sell applications which create, load, or write GEML-compliant files; or distribute or sell your own GEML-compliant files. You may transmit verbatim copies of the GEML DTD to any person if the entire original DTD file is transmitted and the recipient accepts the terms and conditions of this GEML Terms of Use.
You may not modify, lease, loan, sell, distribute, charge for, or create derivative works of the GEML DTDs, without written permission from Rosetta Inpharmatics."
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GenomeWeb
NIH Negotiating with Celera for Access to Celera's Database"A new chapter in the storied and stormy relationship between the National Institutes of Health and Celera Genomics has apparently begun, as NIH officials are now negotiating with Celera for terms of access to its genome database, a NIH spokesman told GenomeWeb Friday."
"If NIH scientists do gain access to Celera's database - at the price of between $7,000 and $15,000 per head - they would effectively be paying for a souped-up version of their own Human Genome Project research published in GenBank, plus Celera's own sequencing research."
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Wired News
Leading the Biotech Pack Upward"A gigantic health care investor conference in the city seems to have instigated a rally in the biotech market when one of the industry's big players reports on its improved fortunes.
The upturn of stock prices was lead by Celera Genomics (CRA ), the company that mapped the human genome in 2000, after officials said they had signed up three more customers for its multi-million-dollar proprietary databases."
""The stock is up today mostly because of the three new subscriptions," said ING Barings analyst Paul Kelly, noting that Celera said on Tuesday it had signed up French genomics firm Genset."
"Biotech deals announced in the last few days highlight the hottest debate in the biotech world: If and how bioinformatics companies -- the likes of Gene Logic (Nasdaq: GLGC), Incyte Genomics (Nasdaq: INCY), and Celera Genomics (NYSE: CRA) -- can sustain long-term business success. Can they sell their information alone, obtain future milestone payments and royalties on drugs or diagnostics produced from their data, or must they become drug development companies themselves?"
"Currently, big pharma subscribers are paying several million dollars per year, for several years, on a non-exclusive basis. Now if we assume you are correct in that unvalidated targets are worth MUCH less than validated targets (and I'm correct in assuming that first generation genomics targets are evn more likely to be "low margin") then, considering the time it will take to bring an unvalidated target to market, Celera is ripping these guys off (well, that's a little extreme). There's absolutely no guarantee any of this data will yield blockbuster drugs and yet they can charge tens of millions of dollars for it on a non-exclusive basis. Why does pharma buy it? Because several million a year is pocket change for a lot of these companies. Why risk missing out? Suckers.;-)
I realize I'm taking an extreme stance, but it's only to make a point: Celera is making a lot of money from their subscribers. The big question is can they continue to sign companies up at a rate sufficient to fund expansion of an internal drug discovery platform. Here we may have a problem. The subscription rate has been, for most of us, disappointing. Either Celera is going to have to start validating targets (or annotating or value-adding) to attract more customers, or they are going to have to enter into significant collaborations. I think they're going to do both."