Next Generation Sequencing—Pass the Pipeline, Please

August 25th, 2009 by Nancy Miller Latimer, M.S.

The drug discovery landscape has morphed into a larger playing field.  Move over small molecule; make room for biologics, diagnostics, biomarkers, and translational research–all key players as medicine gets personal and the division between research and the clinic narrows.  The “one drug, many people” paradigm now has a sibling “one person – just the right drug” paradigm.   Deep sequencing is a technology that figures prominently in the new birth.

As large pharma scrambles to figure out what the new landscape will mean for them, they (1) have reorganized along therapeutic lines with translational research and biomarker departments and (2) have placed their orders for or taken delivery of the next generation of sequencers. And this is not just pharma that is interested.  Biotech, academic and commercial core sequencing facilities, and government research organizations worldwide are actively acquiring the next generation of sequencers—no one wants to be left out.  Obama has pumped billions of dollars into US research.  At some point, sizable chunks will find their way into sequencing facilities[1].

The deep sequencing technologies have moved very fast, while the price of sequencing a human genome has plummeted.  It is no surprise that this inverse relationship is fueling sequencer sales and some anxiety about analyzing all those reads.  The price of sequencing a human genome will soon be under $1K.  “…the much-discussed goal of the $1,000 genome could be attained in two or three years. That is the cost, experts have long predicted, at which genome sequencing could start to become a routine part of medical practice.”[2] An intense desire for an unprecedented “look” into the genome, coupled with analytic inexperience, has created an unmet need in the marketplace.  Hardware vendors are keen to make NGS[3] data analysis as user-friendly as possible, setting the stage for a perfect Pipeline Pilot application.

Accelrys has been investing in a pipelining solution for NGS for over a year now.  Pipeline Pilot is an integration backbone for many hard-working scientific “collections” and third party applications.  Many IT and domain scientists are “hooked” on Pipeline Pilot to deploy robust and easily modified “protocols”.  I know from firsthand experience about the Pipeline Pilot “addiction”.  Oh, and if you aren’t aware, Pipeline Pilot is not just about chemistry anymore.  Complementing our released collections for Imaging, Sequence Analysis, Gene Expression, Plate Data Analytics, and Mass Spec for Proteomics, we look forward to releasing on our first version of our NGS Collection.   You can expect the same drag and drop functionality that you have come to expect and enjoy with the other Pipeline Pilot Collections.

In our first version of our NGS collection, we are making choices about which use cases to support. I am in the process of collecting input from our customers and those awaiting this new product—but I’d like to hear from you, too.  Do your plans for NGS analysis include cloud computing?  If you would like to participate in this survey, please send your name and contact information to me at nlatimer@accelrys.com.  Also, if you are interested in being an alpha or beta tester, let me know!

[1] http://blogs.wsj.com/health/2009/07/08/genetist-francis-collins-nominated-to-head-nih/

[2] http://www.nytimes.com/2009/08/11/science/11gene.html?_r=1&hp

[3] NGS stands for Next Generation Sequencing

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A Man with 5 Rules

August 12th, 2009 by Nancy Miller Latimer, M.S.

Chatting with Christopher Lipinski at Drug Discovery & Development Week

Some ten years ago, I first “met” the Lipinski rules in a software project.  That was my last direct “hands-on” encounter with chemistry.  At Accelrys I am the senior product manager for the Biosciences and Analytics Collections for Pipeline Pilot.  Think genomics, proteomics, sequencing, and ontologies and not chemistry!  This week I was at the DDDW show in Boston – don’t think “booth babe”.

The conference was not as busy this year as it had been in the past and it was the afternoon of the last day.  A distinguished gentleman walked up to our booth wearing a name tag of “Christopher A. Lipinski,” happy to see a fellow booth dweller.   Half in jest I asked if he might be the man with 5 rules.  Turns out he was and, boy, I was in for an intellectual treat.   That Lipinski filter came to life in a new way over the next hour or so.  I was spell bound by Dr. Lipinski’s breadth of knowledge, passion for science, and his out of the box thinking.  What I didn’t anticipate were his insights into the importance of chemistry for the biomarker and translational research space.

He was saying some really awesome things so I started writing them down.    It was hard to focus on note taking because Dr. Lipinski is an excellent speaker and very animated.  Below are a few items that I am willing to share in no particular order:

  • Translational research must have good chemistry married to good biology.
  • Your company (Accelrys) combines chemistry and biology in one software application.  If biologists are using your software to look at high throughput screening (assay) data that has associated chemical structures, they could better filter out results for poor compounds.
  • When faced with people problems (like chemistry—biology conflicts) versus technical problems—the people problems are always much more difficult to solve.
  • The people side is the most important.
  • NIH is making good strides in the dialog between chemists and biologists.
  • As soon as the biologist has an assay for a small molecule they should probe/stress test the assay with compounds known historically to cause assay problems.
  • In software for the (bench) biologist – it needs to be dead easy.  Too many peer-reviewed publications have great biology but rotten chemistry.
  • Biologically active compounds are tightly clustered in chemical space.  It is always best to look for new activity in areas of chemical space where you previously found activity.
  • It takes 10 years to “mature” a medicinal chemist.  He then becomes an expert in pattern recognition even if he can’t articulate why certain structures look better than others
  • Areas of interest
    • Stem cell (non-embryonic source)  derived screening application
    • Many previously proprietary databases are now in the public domain  (See PMID:  17897036).  These provide a great starting point for the discovery of drugs for rare diseases.

Dr Lipinski’s long and prestigious career in medicinal chemistry, assay development, computational chemistry, and now in consulting, lecturing, and as an expert witness does not look anything like retirement.  That is good news for me.

Dr. Lipinski is shown here with his rapt audience.

Dr. Lipinski is shown here with his rapt audience.

Note: Lipinski’s total number of rules actually equals 4.  His rules are known as the “Rule of Five” because each of them incorporates the number 5 in some way.  For all you literalists out there, “5 Rules” should be interpreted in this way.

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