Introduction To Bioinformatics

by Lesk, Arthur M.

• ISBN13: 9780199277872
• ISBN10: 0199277877
• Edition: 2nd
• Format: Paperback
• Copyright: 2005-05-12
• Publisher: Oxford University Press

Summary

On 26 June 2000, the completion of the draft sequence of the Human Genome saw the sciences of biology and medicine change forever. It promised new insights into how our genes shape who we are, and how we function. At the heart of this breakthrough lies a scientific discipline that is now one of the most important knowledge-building tools in current molecular and cellular biology, and healthcare development: bioinformatics.

Table of Contents

Plan of the book	xix
Introduction	1	(66)
Life in space and time	3	(1)
Evolution is the change over time in the world of living things	4	(2)
Dogmas: central and peripheral	6	(3)
Observables and data archives	9	(5)
Information flow in bioinformatics	12	(1)
Curation, annotation, and quality control	13	(1)
The World Wide Web	14	(2)
Electronic publication	15	(1)
Computers and computer science	16	(5)
Programming	17	(4)
Biological classification and nomenclature	21	(3)
Use of sequences to determine phylogenetic relationships	24	(8)
Use of SINES and LINES to derive phylogenetic relationships	30	(2)
Searching for similar sequences in databases: PSI-BLAST	32	(8)
Introduction to protein structure	40	(11)
The hierarchical nature of protein architecture	41	(3)
Classification of protein structures	44	(7)
Protein structure prediction and engineering	51	(1)
Critical Assessment of Structure Prediction (CASP)	52	(1)
Protein engineering	52	(1)
Proteomics	52	(3)
DNA microarrays	53	(1)
Mass spectrometry	54	(1)
Systems biology	54	(1)
Clinical implications	55	(12)
The future	57	(1)
Recommended reading	57	(2)
Exercises, Problems, and Weblems	59	(8)
Genome organization and evolution	67	(50)
Genomes and proteomes	68	(4)
Genes	69	(2)
Proteomes	71	(1)
Eavesdropping on the transmission of genetic information	72	(8)
Mappings between the maps	77	(1)
High-resolution maps	78	(2)
Picking out genes in genomes	80	(1)
Genomes of prokaryotes	81	(6)
The genome of the bacterium Escherichia coli	82	(3)
The genome of the archaeon Methanococcus jannaschii	85	(1)
The genome of one of the simplest organisms: Mycoplasma genitalium	86	(1)
Genomes of eukaryotes	87	(9)
The genome of Saccharomyces cerevisiae (baker's yeast)	89	(4)
The genome of Caenorhabditis elegans	93	(1)
The genome of Drosophila melanogaster	94	(1)
The genome of Arabidopsis thaliana	95	(1)
The genome of Homo sapiens (the human genome)	96	(5)
Protein coding genes	97	(2)
Repeat sequences	99	(1)
RNA	100	(1)
Single-nucleotide polymorphisms (SNPs)	101	(1)
Genetic diversity in anthropology	102	(2)
Genetic diversity and personal identification	103	(1)
Genetic analysis of cattle domestication	104	(1)
Evolution of genomes	104	(13)
Please pass the genes: horizontal gene transfer	108	(1)
Comparative genomics of eukaryotes	109	(2)
Recommended reading	111	(1)
Exercises, Problems, and Weblems	112	(5)
Archives and information retrieval	117	(40)
Introduction	118	(3)
Database indexing and specification of search terms	118	(2)
Follow-up questions	120	(1)
Analysis of retrieved data	121	(1)
The archives	121	(19)
Nucleic acid sequence databases	122	(2)
Genome databases	124	(1)
Protein sequence databases	124	(4)
Databases of structures	128	(7)
Specialized, or `boutique' databases	135	(1)
Expression and proteomics databases	136	(2)
Databases of metabolic pathways	138	(1)
Bibliographic databases	139	(1)
Surveys of molecular biology databases and servers	139	(1)
Gateways to archives	140	(12)
Access to databases in molecular biology	141	(1)
Entrez	141	(7)
The Sequence Retrieval System (SRS)	148	(1)
The Protein Identification Resources (PIR)	149	(1)
ExPASy---Expert Protein Analysis System	150	(1)
Ensembl	151	(1)
Where do we go from here?	152	(5)
Recommended reading	152	(1)
Exercises, Problems, and Weblems	153	(4)
Alignments and phylogenetic trees	157	(62)
Introduction to sequence alignment	158	(2)
The dotplot	160	(5)
Dotplots and sequence alignments	165	(6)
Measures of sequence similarity	171	(4)
Scoring schemes	171	(4)
Computing the alignment of two sequences	175	(1)
Variations and generalizations	175	(1)
Approximate methods for quick screening of databases	176	(1)
The dynamic programming algorithm for optimal pairwise sequence alignment	176	(6)
Significance of alignments	182	(4)
Multiple sequence alignment	186	(2)
Applications of multiple sequence alignments to database searching	188	(10)
Profiles	189	(2)
PSI-BLAST	191	(2)
Hidden Markov Models	193	(5)
Phylogeny	198	(5)
Phylogenetic trees	203	(16)
Clustering methods	205	(1)
Cladistic methods	206	(1)
The problem of varying rates of evolution	207	(1)
Computational considerations	208	(1)
Recommended reading	209	(1)
Exercises, Problems, and Weblems	210	(9)
Protein structure and drug discovery	219	(72)
Introduction	220	(3)
Protein stability and folding	223	(6)
The Sasisekharan-Ramakrishnan-Ramachandran plot describes allowed mainchain conformations	223	(2)
The sidechains	225	(1)
Protein stability and denaturation	225	(3)
Protein folding	228	(1)
Applications of hydrophobicity	229	(4)
Superposition of structures, and structural alignments	233	(2)
DALI (Distance-matrix ALIgnment)	235	(1)
Evolution of protein structures	236	(2)
Classifications of protein structures	238	(2)
SCOP	239	(1)
Protein structure prediction and modelling	240	(23)
Critical Assessment of Structure Prediction (CASP)	242	(2)
Secondary structure prediction	244	(6)
Homology modelling	250	(2)
Fold recognition	252	(3)
Conformational energy calculations and molecular dynamics	255	(4)
Rosetta	259	(1)
Linus	259	(4)
Assignment of protein structures to genomes	263	(2)
Prediction of protein function	265	(4)
Divergence of function: orthologues and paralogues	266	(3)
Drug discovery and development	269	(22)
The lead compound	271	(2)
Bioinformatics in drug discovery and development	273	(11)
Recommended reading	284	(1)
Exercises, Problems, and Weblems	285	(6)
Proteomics and systems biology	291	(54)
DNA microarrays	293	(8)
Analysis of microarray data	295	(6)
Mass spectrometry	301	(10)
Identification of components of a complex mixture	301	(3)
Protein sequencing by mass spectrometry	304	(2)
Genome sequence analysis by mass spectrometry	306	(5)
Systems biology	311	(2)
Networks and graphs	313	(7)
Network structure and dynamics	318	(2)
Protein complexes and aggregates	320	(4)
Properties of protein-protein complexes	321	(3)
Protein interaction networks	324	(5)
Regulatory networks	329	(16)
Structures of regulatory networks	330	(6)
Structural biology of regulatory networks	336	(3)
Recommended reading	339	(1)
Exercises, Problems, and Weblems	339	(6)
Conclusions	345	(2)
Answers to Exercises	347	(6)
Glossary	353	(4)
Index	357