Introduction to Bioinformatics

by Lesk, Arthur M.

• ISBN13: 9780199251964
• ISBN10: 0199251967
• Format: Paperback
• Copyright: 2002-05-09
• Publisher: Oxford University Press

Summary

Written by a pioneer of the use of bioinformatics in research, the second edition of Introduction to Bioinformatics introduces the student to the power of bioinformatics as a set of scientific tools. Retaining and enhancing the rich pedagogy and lucid presentation of the first edition, thisnew edition explains how to access the data archives of genomes and proteins, and the kind of questions these data and tools can answer. It also discusses how to make inferences from the data archives, how to make connections among them, and how to derive useful and interesting predictions. The bookis accompanied by a fully integrated companion website.

Author Biography

Arthur M. Lesk is Professor of Biochemistry and Molecular Biology at The Pennsylvania State University, USA.

Table of Contents

Plan of the book	xvii
Introduction	1	(61)
A scenario	3	(1)
Life in space and time	4	(1)
Dogmas: central and peripheral	5	(3)
Observables and data archives	8	(3)
Curation, annotation, and quality control	10	(1)
The World Wide Web	11	(3)
The hURLy-bURLy	13	(1)
Electronic publication	13	(1)
Computers and computer science	14	(5)
Programming	15	(4)
Biological classification and nomenclature	19	(3)
Use of sequences to determine phylogenetic relationships	22	(9)
Use of SINES and LINES to derive phylogenetic relationships	29	(2)
Searching for similar sequences in databases: PSI-BLAST	31	(8)
Introduction to protein structure	39	(9)
The hierarchical nature of protein architecture	40	(3)
Classification of protein structures	43	(5)
Protein structure prediction and engineering	48	(2)
Critical Assessment of Structure Prediction (CASP)	49	(1)
Protein engineering	50	(1)
Clinical implications	50	(12)
The future	53	(1)
Recommended reading	54	(1)
Exercises, Problems, and Weblems	55	(7)
Genome organization and evolution	62	(53)
Genomics and proteomics	62	(7)
Genes	63	(2)
Proteins	65	(1)
Proteomes	66	(3)
Eavesdropping on the transmission of genetic information	69	(8)
Mappings between the maps	71	(3)
High-resolution maps	74	(3)
Picking out genes in genomes	77	(1)
Genomes of prokaryotes	78	(5)
The genome of the bacterium Escherichia coli	78	(4)
The genome of the archaeon Methanococcus jannaschii	82	(1)
The genome of one of the simplest organisms: Mycoplasma genitalium	83	(1)
Genomes of eukaryotes	83	(10)
The genome of Soccharomyces cerevisiae (baker's yeast)	86	(3)
The genome of Coenorhabditis elegans	89	(1)
The genome of Drosophila melanogaster	90	(2)
The genome of Arabidopsis thaliana	92	(1)
The genome of Homo sapiens (the human genome)	93	(4)
Protein-coding genes	94	(2)
Repeat sequences	96	(1)
RNA	97	(1)
Single-nucleotide polymorphisms (SNPs)	97	(3)
Genetic diversity in anthropology	100	(2)
Genetic diversity and personal identification	101	(1)
Genetic analysis of cattle domestication	101	(1)
Evolution of genomes	102	(13)
Please pass the genes: horizontal gene transfer	106	(2)
Comparative genomics of eukaryotes	108	(1)
Recommended reading	109	(1)
Exercises, Problems, and Weblems	110	(5)
Archives and information retrieval	115	(45)
Introduction	115	(3)
Database indexing and specification of search terms	115	(2)
Follow-up questions	117	(1)
Analysis of retrieved data	117	(1)
The archives	118	(20)
Nucleic acid sequence databases	118	(3)
Genome databases	121	(1)
Protein sequence databases	121	(4)
Databases of structures	125	(8)
Specialized, or `boutique' databases	133	(1)
Expression and proteomics databases	134	(2)
Databases of metabolic pathways	136	(1)
Bibliographic databases	137	(1)
Surveys of molecular biology databases and servers	138	(1)
Gateways to archives	138	(18)
Access to databases in molecular biology	139	(1)
ENTREZ	139	(9)
The Sequence Retrieval System (SRS)	148	(2)
The Protein Identification Resource (PIR)	150	(3)
ExPASy-Expert Protein Analysis System	153	(2)
Ensembl	155	(1)
Where do we go from here?	156	(4)
Recommended reading	157	(1)
Exercises, Problems, and Weblems	157	(3)
Alignments and phylogenetic trees	160	(56)
Introduction to sequence alignment	160	(1)
The dotplot	161	(6)
Dotplots and sequence alignments	167	(5)
Measures of sequence similarity	172	(3)
Scoring schemes	172	(3)
Computing the alignment of two sequences	175	(3)
Variations and generalizations	177	(1)
Approximate methods for quick screening of databases	177	(1)
The dynamic programming algorithm for optimal pairwise sequence alignment	178	(6)
Significance of alignments	184	(3)
Multiple sequence alignment	187	(1)
Structural inferences from multiple sequence alignments	188	(1)
Applications of multiple sequence alignments to database searching	189	(7)
Profiles	190	(2)
PSI-BLAST	192	(2)
Hidden Markov Models (HMMs)	194	(2)
Phylogeny	196	(4)
Phylogenetic trees	200	(16)
Clustering methods	201	(3)
Cladistic methods	204	(1)
The problem of varying rates of evolution	205	(1)
Computational considerations	206	(1)
Recommended reading	207	(1)
Exercises, Problems, and Weblems	208	(8)
Protein structure and drug discovery	216	(61)
Introduction	216	(3)
Protein stability and folding	219	(6)
The Sasisekharan-Ramakrishnan-Ramachandran plot describes allowed mainchain conformations	219	(2)
The sidechains	221	(1)
Protein stability and denaturation	221	(3)
Protein folding	224	(1)
Applications of hydrophobicity	225	(5)
Superposition of structures, and structural alignments	230	(2)
DALI (Distance-matrix ALlgnment)	232	(1)
Evolution of protein structures	233	(1)
Classifications of protein structures	234	(3)
SCOP	236	(1)
Protein structure prediction and modelling	237	(21)
Critical Assessment of Structure Prediction (CASP)	238	(2)
Secondary structure prediction	240	(5)
Homology modelling	245	(2)
Fold recognition	247	(4)
Fold recognition at CASP2000	251	(1)
Conformational energy calculations and molecular dynamics	251	(4)
ROSETTA	255	(1)
LINUS	255	(3)
Assignment of protein structures to genomes	258	(2)
Prediction of protein function	260	(3)
Divergence of function: orthologues and paralogues	261	(2)
Drug discovery and development	263	(14)
The lead compound	266	(2)
Computer-assisted drug design	268	(3)
Recommended reading	271	(1)
Exercises, Problems, and Weblems	272	(5)
Conclusions	277	(1)
Index	278