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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.
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Why
do you think your paper is highly cited?
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“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.”
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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.
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.
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 he lps
guide the choice of computational
methods to find such
sequences.
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.
Casey M. Bergman, Ph.D.
Royal Society USA Research Fellow
Department of Genetics
University of Cambridge
Cambridge, UK
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ESI Special Topics,
January 2005
Citing URL - http://www.esi-topics.com/nhp/2005/january-05-CaseyBergman.html
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