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BRENNER
Steven
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University of California,
461 Koshland Hall, #3102, Berkeley, CA
94720-3102
title:
Challenges in genome annotation
Functional
description of the complete repertoire of proteins
encoded by a genome lies at the core of genomic
biology. In general, one accepts genome sequence,
gene predictions, and gene annotation as reliable
sources from which biological inferences may be
drawn and further experiments devised. However,
computational functional characterization is
fraught with challenges and the ultimate result is
often of questionable reliability.
In this session,
I will review the typical steps in genome
annotation, indicating which steps are reliable and
which remain a challenge. We will make a case study
of the annotation of M. genitalium, where multiple
groups annotations provide us with the
ability to gain some measure of the accuracy of
genome annotation. A second case study will explore
a set of proteins which are both transmembrane and
transcription factors, as an example of the
incredible challenge of making meaningful
functional predictions. The session will conclude
with discussion of approaches that may make
functional annotation more reliable and
valuable.
References
(available at
http://compbio.berkeley.edu/people/brenner/pubs/):
- Brenner SE.
1999. Errors in genome annotation. Trends in
Genetics 15:132-133.
- Zupicich J,
Brenner SE, Skarnes WC. 2001. Computational
prediction of membrane-tethered transcriptions
factors. Genome Biology
2:research0050.1-0050.6.
- Brenner SE,
Chothia C, Hubbard TJP. 1998. Assessing sequence
comparison methods with reliable
structurally-identified distant evolutionary
relationships. Proceedings of the National
Academy of Sciences of the United States of
America 95:6073-6078.
- Brenner SE,
Hubbard T, Murzin A, Chothia C. 1995. Gene
duplications in the H. influenzae genome.
Nature 378:140.
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BRENNER
Steven
|
University of California,
461 Koshland Hall, #3102, Berkeley, CA
94720-3102
title:
Structural genomics of proteins and RNA
Structural
genomics aims to provide a good experimental
structure or computational model of every tractable
protein in a complete genome. Underlying this goal
is the immense value of protein structure,
especially in permitting recognition of distant
evolutionary relationships for proteins whose
sequence analysis has failed to find any
significant homolog. A considerable fraction of the
genes in all sequenced genomes have no known
function, and structure determination provides a
direct means of revealing homology that may be used
to infer their putative molecular function. The
solved structures will be similarly useful for
elucidating the biochemical or biophysical role of
proteins that have been previously ascribed only
phenotypic functions. More generally, knowledge of
an increasingly complete repertoire of protein
structures will aid structure prediction methods,
improve understanding of protein structure, and
ultimately lend insight into molecular interactions
and pathways.
In this session,
I will begin by outlining the basic principles
underlying structural genomics. Methods to be
discussed include target selection and structure
analysis. I will review the classifications used to
analyze solved protein and RNA structures. I will
review progress from structural genomics to date
and provide an outline of expectations for
structural genomics.
References
(available at
http://compbio.berkeley.edu/people/brenner/pubs/):
- Brenner SE.
2001. A tour of structural genomics. Nature
Reviews Genetics 2:801-9.
- Brenner SE.
2000. Target selection for structural genomics.
Nature Structural Biology, Structural Genomics
supplement. 7:967-969.
- Brenner SE,
Levitt M. 2000. Expectations from structural
genomics. Protein Science. 9:197-200.
- Murzin AG,
Brenner SE, Hubbard T, Chothia C. 1995. SCOP: a
structural classification of proteins database
for the investigation of sequences and
structures. Journal of Molecular Biology
247:536-540.
- Klosterman
PS, Holbrook SR, Brenner SE. 2002. SCOR: a
structural classification of RNA database.
Nucleic Acids Research 30:392-394.
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ADDITIONAL DATA
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HTTP LINKS & References:
URLs
References
- Molecular
structure, classification &
evolution
- Murzin AG, Brenner SE,
Hubbard T, Chothia C. 1995. Scop: a structural
classification of proteins database for the
investigation of sequences and structures.
Journal of Molecular Biology
247:536-540.
- Brenner SE, Chothia C,
Hubbard TJP. 1997. Population statistics of
protein structures. Current Opinion in
Structural Biology 7:369-376.
- Brenner SE, Chothia C,
Hubbard TJP, Murzin AG. 1996. Understanding
protein structure: Using SCOP for fold
interpretation. Chap. 37 in: Doolittle RF, ed.
Computer Methods for Macromolecular Sequence
Analysis. Methods in Enzymology. Vol. 266.
Orlando, FL: Academic Press.
635-643.
- Klosterman PS,
Holbrook SR, Brenner SE. 2002. SCOR: a
structural classification of RNA database.
Nucleic Acids Research. in
press.
- Reliable pairwise
sequence comparison
- Chandonia JM, Walker
NS, Lo Conte L, Koehl P, Levitt M, Brenner SE.
2002. ASTRAL compendium enhancements. Nucleic
Acids Research. in press.
- Brenner SE, Chothia C,
Hubbard TJP. 1998. Assessing sequence comparison
methods with reliable structurally-identi?ed
distant evolutionary relationships. Proceedings
of the National Academy of Sciences of the
United States of America
95:6073-6078.
- Genome annotation
challenges
- Brenner SE. 1999.
Errors in genome annotation. Trends in Genetics
15:132-133.
- Brenner SE, Hubbard T,
Murzin A, Chothia C. 1995. Gene duplications in
the H.influenzae genome. Nature
378:140.
- Zupicich J, Brenner
SE, Skarnes WC. 2001. Computational prediction
of membrane-tethered transcriptions factors.
Genome Biology
2:research0050.1-0050.6.
- Structural
genomics
- Brenner SE. 2001. A
Tour of Structural Genomics. Nature Reviews
Genetics 2:801-9.
- Brenner SE. 2000.
Target selection for structural genomics. Nature
Structural Biology, Structural Genomics
supplement. 7:967-969.
- Brenner SE, Levitt M.
2000. Expectations from structural genomics.
Protein Science 9:197-200.
- Brenner SE, Barken D,
Levitt M. 1999. The PRESAGE database for
structural genomics. Nucleic Acids Research.
27:251-253.
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