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New Hot Paper Comments

By Casey Bergman

ESI Special Topics, January 2005
Citing URL - http://www.esi-topics.com/nhp/2005/january-05-CaseyBergman.html

Casey Bergman answers a few questions about this month's new hot paper in the field of Computer Science.


From •>>January 2005

Field: Computer Science
Article Title: Benchmarking tools for the alignment of functional noncoding DNA - art. no. 6
Authors: Pollard, DA;Bergman, CM;Stoye, J;Celniker, SE;Eisen, MB
Journal: BMC BIOINFORMATICS
Volume: 5
Page: 
Year: JAN 21 2004
* Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Dept Genome Sci, Berkeley, CA 94720 USA.
* Univ Calif Berkeley, Lawrence Berkeley Lab, Div Life Sci, Dept Genome Sci, Berkeley, CA 94720 USA.
* Univ Calif Berkeley, Biophys Grad Grp, Berkeley, CA 94720 USA.
* Univ Calif Berkeley, Lawrence Berkeley Lab, Berkeley Drodophila Genome Project, Berkeley, CA 94720 USA.
* Univ Bielefeld, Tech Fak, D-33594 Bielefeld, Germany.
* Univ Calif Berkeley, Dept Mol & Cell Biol, Berkeley, CA 94720 USA.
* Univ Cambridge, Dept Genet, Cambridge CB2 3EH, England.

ST:  Why do you think your paper is highly cited?


“Our study presents the first detailed  performance evaluation of a set of computational methods used to  compare DNA sequences that do not encode proteins -- so-called  "noncoding" sequences -- which make up the majority of sequences in  animal genomes, including our own.”

Our study provides a detailed performance evaluation for a number of widely-used programs in the field of DNA sequence comparison—the alignment of functional noncoding sequences. Identifying conserved noncoding sequences is a commonly used computational approach for detecting regulatory sequences that control gene expression, and many new alignment methods have been developed in the last few years to solve this problem. Until recently, there has been no serious attempt by (or incentive for) developers to evaluate the performance of a new alignment method. We approached the problem of aligning noncoding sequence comparisons from a user's perspective rather than a developer's perspective, giving an assessment that is of interest to a range of researchers, from developers to bench biologists. I believe the real merit of the work is its practical utility—providing an evaluation of a timely methodological question that many biologists face and to which they would like to know the answer.

ST:  Does it describe a new discovery or a new methodology that's useful to others?

Our study uses evolutionary simulations to evaluate the performance of alignment tools—a powerful technique which has been applied to protein-coding sequences—but until our study had not been applied to functional noncoding sequences. We do present an updated simulation method and new ways to measure alignment performance, but the impact of the work is in providing an independent performance evaluation of different tools for the alignment of functional noncoding DNA.

ST:  Could you summarize the significance of your paper in layman's terms?

Computational biology is currently experiencing a rapid growth phase, with large-scale biological datasets and novel computational methods being published at an ever-increasing rate. Choosing the appropriate computational tool for a given biological problem is a situation researchers now regularly encounter, often spending substantial time and effort installing and evaluating different software when they would rather be analyzing their data. Our study presents the first detailed performance evaluation of a set of computational methods used to compare DNA sequences that do not encode proteins, so-called "noncoding" sequences, which make up the majority of sequences in animal genomes, including our own. Noncoding sequences that are conserved between species can predict as-yet-unidentified functionally important sequences such as those that regulate gene expression, and our study helps guide the choice of computational methods to find such sequences.

ST:  How did you become involved in this research?

During my Ph.D. studies, I conducted a "pre-genomic" study of noncoding sequence conservation of the genus Drosophila, in which it became clear that different alignment methods gave substantially different results. Since the new alignment methods being published at the time provided little direct comparison with each other, I had difficulty addressing the question of which tool could produce the most accurate noncoding sequence alignments. Conversations with other researchers made it clear that this was an issue I was not alone in facing, especially with new genome data coming online, so I decided to initiate a project that addressed this question directly.End

Casey M. Bergman, Ph.D.
Royal Society USA Research Fellow
Department of Genetics
University of Cambridge
Cambridge, UK

ESI Special Topics, January 2005
Citing URL - http://www.esi-topics.com/nhp/2005/january-05-CaseyBergman.html

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