SciLink Blog

Tom, Can you tell us a little about your background? how did you get into science and interested in a system’s approach?

As an undergrad at the University of Wisconsin I pursued dual interests in biology and English literature. I came across Lynn Margulis and Dorian Sagan’s Microcosmos, a wonderful treatise on the role of symbiosis in eukaryotic evolution, and wanted to pursue a few ideas on the putative bacterial origin of the structural protein tubulin. Fortunately, I was at Wisconsin during the late 1980’s, which was a great place to be during the seminal years of bioinformatics. Two pioneering sequence analysis software companies, the Genetics Computer Group (GCG, currently Accelrys) and DNASTAR, sprang out of efforts to sequence Escherichia coli at Wisconsin; GCG by John Devereaux and DNASTAR by Fred Blattner. With this backdrop I began to pursue my nascent ideas in sequence analysis and symbiosis.
I completed an undergraduate thesis on the molecular evolution of tubulin under the guidance of Dr. Gary Borisy (an expert in tubulin and cell division) and Dr. Ann Palmenberg (an expert in RNA picornaviruses). Ann taught and organized a seminar series in Bioinformatics, which was likely among the first classes in the country. She worked with John Devereaux to bring in many of the heavyweights in Bioinformatics; both for the seminar series and to collaborate with GCG. I took the class three times and was taught early sequence analysis theory by Michael Zucker (RNA folding), Steven Altschul (BLAST), Temple Smith (Smith-Waterman alignment), Walter Fitch (molecular phylogeny), James Crow (neutral theory of evolution) and many others. The undergraduate thesis did not lend itself to any spectacular results, presumably due to a combination of my inexperience, an exceedingly small database of protein sequences (Genpept was around 40,000 sequences in 1990) and the lack of a structure-based phylogenetic approach. Later, Linda Amos and Jan Löwe, would show that there was indeed a strong structural similarity between tubulin and bacterial ftsZ structural proteins, although symbiosis may not needed to explain this event as later transfer is just as likely.
My undergraduate work did, however, give me a taste of bioinformatics and sequence analysis which would lead me to Boston University and BG Medicine. After graduating Wisconsin, I took a role at DNASTAR in sales and technical support and shortly transitioned into technical writing. After a time I grew tired of describing bioinformatics tools and wanted to develop and apply them myself. With Fred Blattner’s (head of the E.coli genome project and DNASTAR’s founder/CEO) encouragement and support I joined Temple Smith’s group—the BioMolecular Engineering Research Center (BMERC)—in the fall of 1996.

Tell us a little about your experience in graduate school and your interest in bioinformatics

I was again extremely fortunate to be at the BMERC during the late 1990s. The lab had a number of research interests, anywhere from sequence analysis (dynamic programming, Bayesian prior-profiles) to protein structure prediction (homology modeling, threading) to molecular phylogeny. The Institute for Genomic Research (TIGR) was beginning to rapidly complete multiple bacterial genomes and eukaryotic genomes were in sight. This afforded a tremendous opportunity in comparative sequence analysis. Under Temple’s leadership and an extremely bright group of post-docs, students and collaborators we were able to accomplish a lot of guerilla science (get in, make your mark, get out before the big-boys arrive), including a technical comment in Science on Genome Excess plots in my second year in the lab.
The environment at BMERC was quite different than many graduate experiences. Temple encouraged debate at all levels and collaboration within and outside of the group. He can still beat most of his students with a gigantic library of existing codes (“I’ve already done that in Fortran…”). His piped combinations of Sed, Awk, Sort and Comm are still semi-legendary.
I finished my dissertation work applying prior-profile analysis to proteins involved in mitochondrial pathologies. This work highlighted the great degree of sequence and structural conservation among the mitochondrial proteome and the consequences for modifying key residues in critical locations.

After BMERC you joined Beyond Genomics now BG-Medicine what do you do there?

After graduating I joined Beyond Genomics, a Waltham, Massachusetts based systems biology start-up. In those days BG was more of a technology shop interested in developing mass spectroscopy approaches to measuring systems, primarily in plasma. We also did a lot of work developing the computational, statistical and bioinformatics architecture necessary to support such efforts. Eric Neumann (Clinical Semantics Group), Matej Oresic (VTT, Finland) and I created correlation networks as a way to take advantage of mathematical associations in cross-omics data. The key advantage of such an approach is the ability to annotate and understand poorly-characterized analytes as well as well-characterized analyte within the context of a single experiment. This approach became extremely useful in evaluating novel mechanisms of disease development and drug interaction, biomarker discovery and circulating biomarkers of tissue effect.
I took over leadership of the group from 2003-2006 and have since moved on to direct the project planning & data interpretation group at BG Medicine (Beyond Genomics changed its name to BG Medicine in the fall of 2004). In this role I have greater responsibilities for experimental design as well as the back end of bioinformatics and general biocontextualization (a fancy systems biology term for attempting to place findings into an appropriate biology context). This included primary scientist roles in our Liver Toxicity Biomarker Study (LTBS) and our High-Risk Plaque consortium (HRP).

What you believe is the definition of system’s biology and how a system’s approach will aid clinicians and pharma in getting to a diagnosis and treatment?

Hiroaki Kitano, Lee Hood and Doug Lauffenburger still have the best definitions for Systems Biology. From Kitano’s review in Science in 2002 he described systems biology in terms of four properties: system structures, system dynamics; the control method and the design method. This view is fairly complementary to Lauffenburgers’s 4M model: measure, mine, model, manipulate. The problem is that, with the exception of very narrowly defined systems, we’re still in the first two stages: measuring all of the omics data you can and trying to determine the relationship among the measured analytes. Having a good understanding of network control and manipulating networks is still a ways, off, at least for most of the problems that clinicians and the pharmaceutical industry is interested in. A few companies (Entelos, Genstruct) are focused on this problem but most of this work is still carried by academics. Some groups are combining systems biology alongside synthetic biology, for example Jim Collins’ and Tim Gardner’s work on mammalian switches and network inference, which look particularly promising.
BG Medicine has taken a more narrow approach in the systems biology space focusing on ‘Systems Pathology’ and ‘Systems Pharmacology’. Systems Pathology is loosely defined as the measurement and interpretation of molecular analytes that change in the disease state. Systems Pharmacology, then, is the measurement and interpretation of molecular analytes that change with a pharmacological perturbation. Under this model measuring system components and their interactions are the keys to elucidating a system under disease burden and drug treatment.
In terms of the ultimate utility of system approaches for medicine, I’d stress the importance of well-conceived experimental designs over sophisticated pathway, network and bioinformatics approaches—yes this is coming from a card-carrying bioinformaticist. So many of the omics studies today are underpowered, making results non-generalizable to larger contexts. Good experiments are costly, however, so this is why small sample sizes are the norm. We spend a lot of time reviewing project objectives prior to carrying out any experiments: is the study sufficiently powered to see univariate markers? Multivariate classifiers? Correlations among analytes? Are we recording the system with the right set of experimental platforms to measure perturbations in disease and drug intervention? Even addressing these concerns there are still a lot of open questions that can interfere with interpretation. Are you measuring at the right time-scale? In the right location? Do you need to fractionate tissues or cells? Does a cell-system accurately recapitulate its environment? Does an animal model accurately recapitulate clinical behavior? I could go on…
The first return on investment using a systems approach will probably occur at the intersection of systems biology with biomarker discovery, likely on the diagnostic front. Biomarkers derived from omics experiments are already in use for disease classification, such as Oncotype Dx® for breast cancer. Therapeutic response is another area where biomarkers can play a role. Predicting responders/non-responders when the disease and drug treatment is known is a much less parameterized space than disease classification and therefore a less daunting target. The holy grail for biomarker utility is an analyte, or small set of analytes, that can be used for diagnosis, prognosis and therapeutic monitoring, for example; this marker would be elevated in diseased individuals over healthy, higher levels indicate a poorer prognosis and drug therapy would decrease biomarker levels over time while outcome improves. Biomarkers of this type are exceedingly rare and to my knowledge, only Galectin-3, a prognostic marker of hear failure, comes close.

Who should reach out to you in SciLink?

I have two primary interests, one in network biology and pathway analysis and a second in biomarker-guided medicine (the ‘BG’ in BG Medicine). I
Some of my thoughts in network biology are better suited for an academic environment, and I hope to develop these further at Northeastern (these concepts were recently published in Drug Efficacy, Safety, and Biologics Discovery: Emerging Technologies and Tools: “Systems Biology, Biomarkers, and Biomolecular Networks”). I’m always interested in bouncing these ideas off like-minded colleagues.
Biomarker adoption throughout the entire therapeutic process is slowing becoming a standard approach. There is a chain of biomarker utility from disease prediction, disease diagnosis, disease prognosis, disease classification, therapeutic selection, therapeutic predictors of response/nonresponse and well as surrogate biomarkers. I’m also interested in discussions around the use of biomarker-guided therapies at both the scientific and business level.

See Tom’s Profile On SciLink

May SciLink Updates and Announcements
File Sharing Comes To SciLink!
We are pleased to announce the addition of file sharing to the SciLink platform. You can now upload files to your profile and send these files to groups that you have joined. If the file is an image, it will become instantly viewable in the new SciLink image viewer. Right now, files are either publicly accessible or only viewable by members of your network. In the future, we’ll be adding a more fine grained permissioning scheme.
We have also added file uploading and sharing to the groups section of SciLink. We believe this will help groups share any pre-publication material, images, word documents, spreadsheets etc. Anything you need to get your work done can be shared in the file upload section on SciLink!
Finally, we have fixed a number of outstanding bugs on the system and made it easier to complete your profile by adding an autocomplete capability in the expertise, school and work sections.
Thanks so much for using SciLink!

We’re switching our servers to Amazon’s cloud. This has been a bit of a slow process and has caused some downtime of our service. We believe that this switch will aid in our future up time, responsiveness and scalability. More importantly, we will be able to better respond and maintain our private channel partner websites by spinning up “clones” of the SciLink service with a flick of a switch. We’re very sorry for the delay and will be up this weekend.

Thanks for your continued patience.

Sincerely,

Brian Gilman
Founder & CEO
SciLink Inc.

Can it be true? Are all of us blue? We’d like to know here at SciLink. Help us out by logging into your account and cast your vote! You need to have an account to vote. We’ll publish our results after we perform our analysis on November 5!

Here’s an interesting tidbit from ScienceBlogs:

In the latest issue of Science, an article on grass-roots efforts by scientists in the last weeks before the election brought up a startling point, that there have been a lot of letters to the Editor and OpEds published in newspapers either endorsing Obama or pointing out the errors of the McCain campaign rhetoric on science. What is absolutely amazing, is that there has not been a single letter or OpEd by a scientist endorsing McCain. Not ONE? Here is a partial list of OpEds and letters that have appeared. This is by no means a comprehensive list. In fact, these are almost all in battleground states. This is a really unusual thing to happen in an election and should be appreciated for sheer volume.

Truly Amazing - Enough Said…

If you haven’t heard, we recently updated the site with events, meetings and conference listings. At SciLink we’re trying hard to keep you up to date with the scientific world and your network. We do this in a number of different and complementary ways. First, your dashboard is a portal into all the activity in SciLink. We feed global activity to you: new jobs, events and groups that have been created so you know what’s going on in the SciLink community and don’t need to go to a hundred web pages to try and figure it out for yourself. Next, we roll up your network’s activity by funneling the papers your network is reading, events they are attending and groups they’ve joined. All these features let you keep abreast of what’s going on in your community.

The event, conference and meetings part of our site gets you even more connected by allowing you to plan and share what meetings and events you are interested in. It even helps find events that you might never have known about before!

Right now SciLink lets you rate and create comments for events you’re attending. We plan on more interesting features in the near future. So, why not take a look right now? It’s simple to get started! Click here to see a listing of conference, events and meetings!

If you’re planning a meeting or event head on over and post and event today!. SciLink is a great way to get the word out!

This is an unprecedented amount of money to provide to a research institution. I think people forget just how amazing Eric Lander is as an executive and business person. You couldn’t ask for a better science based executive. Read below:

Less than five years into a ten-year groundbreaking experiment in philanthropy and science, the results are in. The Broad Institute of Harvard and MIT, which was founded in 2003 and launched in 2004 to test how effective venture philanthropy and inter-institutional collaboration could be in propelling biomedical progress, has been declared a resounding success, and will now become a permanent, standalone institution within the biomedical landscape.
At today’s celebration of its anniversary, the Broad Institute of Harvard and MIT received an unprecedented gift from its philanthropic founding partners Eli and Edythe L. Broad: an endowment intended to establish the Broad Institute of MIT and Harvard as a permanent biomedical research organization. Eli and Edythe Broad announced their gift this morning at a ceremony featuring speeches by Governor Deval Patrick of Massachusetts, MIT President Susan Hockfield, Harvard President Drew Gilpin Faust, Nobel Laureate David Baltimore of Caltech, and Broad Institute director Eric Lander.
The unequalled $400 million endowment gift brings the Broads’ total commitment to $600 million. The gift is a testament to the success of the institute’s new model of research collaboration that spans the entire MIT and Harvard communities, including the 17 Harvard-affiliated teaching hospitals. This model of collaboration aims to accelerate the pace of scientific progress and make data and tools rapidly and freely available. In its short history, the Broad Institute’s accomplishments include cataloging and identifying genetic risk factors for diseases such as type 2 diabetes and autism; discovering new therapeutic targets for cancer, malaria, and other diseases; and applying genomic tools to better understand and treat human pathogens like tuberculosis.
“Of all of our philanthropy, the Broad Institute has been the investment that has yielded the greatest returns,” said Eli Broad, founder of The Eli and Edythe Broad Foundation. “This truly is a new way of doing science, and the Institute’s unique collaborative model for scientific research has resulted in remarkable accomplishments in a very short period of time. Although this is a large gift – the largest that we have ever made – it is only a fraction of what will be needed to unlock the enormous promise of biomedical research at MIT and Harvard. We are counting on others to step forward as partners in the next phase of this grand experiment. We are convinced that the genomics and biomedical work being conducted here by the world’s best and brightest scientists will ultimately lead to the cure and even the prevention of diseases.”
The Broads’ $600 million commitment is the largest to support biomedical research at a university anywhere in the world. The Broads initially invested $100 million in 2003 as a way to test the institute’s new approach to biomedical research. By 2005, the Broad Institute had already made significant accomplishments and progress, and the Broads’ invested a second $100 million. Their endowment of $400 million today will allow the Broad Institute to transition to a permanent, non-profit 510(c)(3) organization with both Harvard and MIT still at the heart of it, continuing to help govern the institute.
“Eli and Edythe Broad are true visionaries,” said Eric Lander, founding director of the Broad Institute. “They made an enormous bet in 2004. Their bet has paid off more handsomely than any of us imagined. It has unleashed the creative potential of a remarkable community of scientists. And, it has defined a new model for how scientists and institutions can work together.”
“There is no place in the world with as great a concentration of life sciences talent, resources, and vision as Massachusetts,” said Deval Patrick (D), Governor of the Commonwealth of Massachusetts. “With this significant endowment of the Broad Institute by Eli and Edythe Broad – and the collaboration and support of the industry, academia, business, and government through the Massachusetts Life Sciences Initiative – we are on our way to helping find new cures for diseases, creating new jobs, and positioning ourselves for long-term economic growth.”
“To fully realize the benefits of the genomic sciences, scientific research must transcend the boundaries of disciplines, departments, and even institutions,” said Harvard University President Drew Gilpin Faust. “Through their continued philanthropy, the Broads have made that transcendence possible. I am grateful for their support of this important work and look forward to continuing our partnership with the Broad Institute.”
“Cambridge and Boston are world-renowned for their creative, scientific minds and unrivaled biomedical community, and the Broad Institute is uniquely positioned to realize the full potential of these intellectual resources,” said Susan Hockfield, president of MIT. “We are profoundly grateful to Eli and Edythe Broad for their generosity and vision, and look forward to continuing our many collaborative research efforts through the Broad Institute and defining the future of the field.”

None of us in the first world have the time. We don’t have the time to do all thing things we’re supposed to do. We’re too busy consuming. Yet one person has made it his life’s work to find the time to make sure the poor get proper healthcare. I have come to know that man through a book called, “Mountains Beyond Mountains”. Which, in Haitian means, “you’re screwed”… I encourage everyone reading this blog post to pick this amazing book up and, if you can find the time, watch this video.

Tony Williams grew up in Wales, UK - and originally considered being a Welsh teacher. However, after speaking with his career master, Tony quickly decided that career path probably wouldn’t lead to a successful career trajectory. Tony went to Liverpool University where he found Honors Level Chemistry fairly boring and spectroscopy especially challenging. He essentially self-taught himself spectroscopy from books and papers and, as fate would have it, Tony’s protons aligned to find his life’s passion in EPR/NMR spectroscopy. He later saw applications for this technology by studying Vitamin E related systems and this sparked a life long interest in NMR spectroscopy. He went on to get his PhD in NMR applying the technique to study lubricant systems at high pressures up to 5kbar.

Tony’s interest in computers and computing started when he was a poor graduate student. He wrote programs while getting his PhD. to analyze NMR relaxation data and installed PC’s in offices around central London. Tony spent some time at The National Research Centre laboratories in Ottawa performing Single Crystal EPR Rochester and finally landed in New York with the Eastman Kodak company. While at Kodak, Tony was the NMR Technology Leader for the company working with a team of almost 10 NMR scientists and almost as many NMR instruments. While at Kodak, he published over 20 papers and received 2 patents. One of his primary challenges was to homogenize instruments, platforms and processes at the company, specifically for walk-up spectroscopy laboratories so they could maximize throughput and ROI for the chemists. Tony was also one of the three people involved with building WIMS, a web-based information management system (http://www1.elsevier.com/homepage/saa/trac/wimsarti.htm) for managing samples, structure and spectra. This system still prevails today.

While at Kodak, Tony formed a close collaborative relationship with Advanced Chemistry Development (ACD/Labs) on a project to develop NMR based software. After a number of extremely fruitful interactions, Tony decided to take his entrepreneurial spirit out of a Fortume 500 company and into the small start-up company and joined ACD (www.acdlabs.com) as their NMR Product Manager. While at ACD/Labs, Tony managed the majority of their product lines with a focus on structure drawing and databasing, systematic nomenclature and analytical spectroscopy and chromatography. During his tenure he held multiple roles and was the Vice President and Chief Science Officer for a number of years. After a decade at ACD/labs and following the adoption of twin boys a couple of years earlier, Tony found that his demanding travel and work schedule didn’t fit the demands of his young family and started to look for other opportunities.

After seeing the efforts of both PubChem and Wikipedia to deliver chemistry-related data to the public his creative nature determined that maybe a combined approach of both efforts could deliver value to chemists worldwide. His initial concept was for a commercial software product that would crawl a network of disks internal to an organization and index chemistry in documents, reports and other files and integrate with data available on the web. However, Tony believes that a free-access website for indexing chemistry would have more value to Chemists. Thus, ChemSpider was born.

Here are excerpts from the interview:

Why did you found ChemZoo and produce ChemSpider?

[My] intention was always to form a community around chemical structures. We’d like to allow users to annotate and tag information around chemical structures to help share their knowledge and reduce the barriers, both cost, time and navigation hurdles, to chemistry related data. Presently we integrate to well over a 100 chemistry data sources with a few tens waiting to be added at present.

Can you give me some statistics on usage right now?
Presently we’re getting around 6000 users per day, and over 20,000 search requests a day (excluding robots). We’ve got over 1100 registered users but no one has to register to use the site. Those registered users however can add comments, deposit structures, spectra and so on.

How is the company funded?
We’re bootstrapping with personal bank accounts. Also, we have some sponsors who have been kind enough to contribute some donations, generally in exchange for us developing a particular aspect of the site such as extending the API.

Do you have a revenue model?
We’re figuring that out right now and have a number of different discussions with companies right now. This project started as a hobby project as I was gainfully employed at the time it started and never saw it as a source of income. Having chosen the path of self-employment as a consultant the potential of ChemSpider generating revenue is of course of interest. My preference is to not charge the users for public access but to obtain grants, maybe advertising revenue and require fees from companies who with to have secure links to the site for mashing results from ChemSpider data queries with their own internal systems. A rich uncle isn’t an option…I’ve looked across my family tree..

How many people work on the site? Are they full time?
[There are] 5 volunteers working on the site - they are involved with the coding, development of the website, algorithms for structure handling, text mining and so on. Then there are the users who help with “crowd sourcing” of data curation and deposition of new data

What do you want the site to be at the end of the day?

I’d like ChemSpider to be the first place people think of for researching information about small molecules. I work with the Wikipedia chemistry team, and I see our efforts to be complementary. We offer more capabilities however in terms of structure-based searching, hosting of analytical data, services for generation of properties, web-services for companies to integrate ChemSpider to their instruments and into their websites. It would be nice to be “ChemSPider Inside” to coin a phrase from Intel. Based on the interest of groups talking to us now you’ll see growth in the number of chemical vendors putting their catalogs online so it can become a public chemical directory for ourcing chemicals. We’re also working on making open access chemistry articles searchable by chemical structure. We’ve already done work with the International Union of Crystallography to make their open access article available via chemical structure searching. Chemspider is already a content system to aid Open Notebook science with thought-leaders like JC Bradley from Drexel university. We’ve just released the ChemSpider forum to allow the chemistry community to exchange information and collaborate. People struggling with synthesis or class of structures can get into collaborations. We are not short of ideas..bottom line though is that ChemSpider is intended to be one of the central communities to enable collaboration around chemistry and chemical structures

How many compounds are in chemspider?
We have 20 million compounds and growing literally daily.

Highlights?
My career highlights are many. I worked with excellent technical people at ACD/Labs and formed a rich network of friends in the community. Working with Dr Gary Martin from Schering Plough to crack a structure elucidation problem that remained unsolved for over a decade was great and the completion of a review article on Computer assisted structure elucidation that took over 18 months to write was just great.

Who should reach out to you in SciLink?
I pay my bills with consultancy so anyone wanting expertise in cheminformatics, systematic nomenclature and applications of software tools to chemistry is welcomed to contact me. In terms of ChemSpider we are always looking to support our users, extend and improve the system and collaborate with people interested in what we’re doing. I’m especially interested in talking to publishers who might want to deposit to ChemSpider and people who might be interested inus hosting their Chemistry information.