Introduction to Bioinformatics (PDF)

Introduction to Bioinformatics
Arthur M. Lesk
Release at: 2014
Pages: 440
4th Edition
File Size: 10 MB
File Type: pdf
Language: English

Description of Introduction to Bioinformatics

The Introduction to Bioinformatics 4th edition by M. Lesk is a great book for studies of Bioinformatics available in PDF (eBook) easy download. The natural habitat of bioinformatics is the web. Previous versions of this book recognized this, to some extent, with an Online Resource Centre supplementing the text. With this 4th edition, the online material assumes a full partnership.

To learn bioinformatics means to understand basic concepts and principles, and to develop a set of skills. The paper text contains an exposition of the concepts and principles; the Online Resource Centre is the equivalent of a ‘laboratory’ or ‘practical’ component of the course. An icon in the text indicates the appearance in the Online Resource Centre of material related to the current discussion.

The data of bioinformatics are accessible on the web. Programs to analyze them are available on the web. Indeed, many authors of programs provide web servers for remote access to the calculations. Links from databases to servers streamline the passage from data retrieval to data analysis. Such facilities supersede the old procedure of ‘download the data onto your computer, install the program on your computer, and run it locally’.

All research in contemporary molecular biology depends on data, and programs to retrieve and analyze them. There is consensus that all biomedical scientists must achieve a minimum of programming skills, but there is vigorous debate over what this minimum level should be. The point of view expressed in this book is that molecular biologists based primarily in a ‘wet’ lab must dip no more than their toes into the stream; those based primarily at a computer must wade in up to their waist perhaps, but only those specializing in computer science and software development must undergo total immersion.

Indeed, one of the arguments for the suggestion that sophisticated programming skills are not generally required is the great panoply of freely available programs, written by acknowledged professionals. What is essential is developing skill in using these programs, and in the intelligent interpretation of the results that they produce.

Content of Introduction to Bioinformatics

1 Introduction

Life in space and time

Phenotype = genotype + environment + life history + epigenetics

Evolution is the change over time in the world of living things

Dogmas: central and peripheral

Statics and dynamics


Observables and data archives

A database without effective modes of access is merely a data graveyard

Information flow in bioinformatics

Curation, annotation, and quality control

The world-wide-web

Electronic publication

Computers and computer science


Biological classification and nomenclature

Use of sequences to determine phylogenetic relationships

Use of LINES & SINES to derive phylogenetic relationships

Searching for similar sequences in databases: PSI-BLAST

Introduction to protein structure

The hierarchical nature of protein architecture

Classification of protein structures

Protein structure prediction and engineering

Critical Assessment of Structure Prediction

Protein engineering

Proteomics and transcriptomics

DNA microarrays

Transcriptomics and RNA sequencing

Mass spectrometry

Systems biology

Clinical implications

The future

Recommended reading

Exercises and problems

2 Genome organization and evolution

Genomes, transcriptomes, and proteomes


Proteomics and transcriptomics

Eavesdropping on the transmission of genetic information

Identification of genes associated with inherited diseases

Mappings between the maps

High-resolution maps

Genome-wide association studies

Picking out genes in genomes

Genome-sequencing projects

Genomes of prokaryotes

The genome of the bacterium Escherichia coli

The genome of the archaeon Methanococcus jannaschii

The genome of one of the simplest organisms like Mycoplasma genitalium

Metagenomics: Coherent environmental sample collection of genomes

The human microbiome

Genomes of eukarya

Gene families

The genome of Saccharomyces cerevisiae (baker's yeast)

The genome of Caenorhabditis elegans

The genome of Drosophila melanogaster

The genome of Arabidopsis thaliana

The genome of (Human) Homo sapiens

Protein-coding genes

Repeat sequences


Single-nucleotide polymorphisms and haplotypes

Systematic measurements and collections of single-nucleotide polymorphisms

Ethical, legal, and social issues

Genetic diversity in anthropology

DNA sequences and languages

Genetic diversity and personal identification

Evolution of genomes

Please pass the genes: horizontal gene transfer

Comparative genomics of eukarya

Recommended Reading

Exercises and problems

3 Scientific archives and publications: media, access, and content

The scientific literature

Economic factors governing access to scholarly publications

Open access

The Public Library of Science

Traditional and digital libraries

How to populate a digital library

The information explosion

The web: higher dimensions

New media: video, sound

Searching the literature

Bibliography management


Database contents

The literature as a database

Database organization


Database quality control

Database access


Database interoperability

Data mining

Programming languages and tools

Traditional programming languages

Scripting languages

Program libraries specialized for molecular biology

Java: computing over the web

Markup languages

Natural language processing

Natural language processing and mining the biomedical literature

Applications of text mining

Recommended reading

Exercises and problems

4 Archives and information retrieval

Database indexing and specification of search terms

Follow-up questions

Analysis and processing of retrieved data

The archives

Nucleic acid sequence databases

Genome databases and genome browsers

Protein sequence databases

Databases of protein families

Databases of structures

Classifications of protein structures

Accuracy and precision of protein structure determinations

Specialized, or ‘boutique’, databases

Expression and proteomics databases

Bibliographic databases

Surveys of molecular biology databases and servers

Gateways to archives

Access to databases in molecular biology


The Protein Identification Resource

ExPASy: Expert Protein Analysis System

Where do we go from here?

Recommended reading

Exercises and problems

5 Alignments and phylogenetic trees

Introduction to sequence alignment

The dot-plot

Dot plots and sequence alignments

Measures of sequence similarity

Scoring schemes

Derivation of substitution matrices: PAM and BLOSUM matrices

Computing the alignment of two sequences

Variations and generalizations

Approximate methods for quick screening of databases

The (DPA) dynamic programming algorithm for optimal pairwise sequence 

Significance of alignments

Multiple sequence alignment

Applications of multiple sequence alignments and database searching



Hidden Markov models


Determination of taxonomic relationships from molecular properties

Phylogenetic trees

Clustering methods

Cladistic methods

Reconstruction of ancestral sequences

The problem of varying rates of evolution

Are trees the correct way to present phylogenetic relationships?

Computational considerations

Putting it all together

Recommended reading

Exercises and problems

6 Structural bioinformatics and drug discovery


Protein stability and folding

The Sasisekharan–Ramakrishnan–Ramachandran plot describes allowed 
mainchain conformations

The sidechains

Protein stability and denaturation

Protein folding

Applications of hydrophobicity

Coiled-coiled proteins

Superposition of structures, and structural alignments


Evolution of protein structures

Classifications of protein structures

Protein structure prediction and modeling

A priori and empirical methods

Critical Assessment of Structure Prediction

Secondary structure prediction

Homology modeling

Fold recognition

Conformational energy calculations and molecular dynamics

Assignment of protein structures to genomes

Prediction of protein function

Divergence of function: orthologues and paralogues

Drug discovery and development

The lead compound

Improving on the lead compound: quantitative structure-activity relationships

Bioinformatics in drug discovery and development

Molecular modeling in drug discovery

Recommended reading

Exercises and problems

7 Introduction to systems biology


Networks and graphs

Connectivity in networks

Dynamics, stability, and robustness

Some sources of ideas for systems biology

Complexity of sequences

Computational complexity

Static and dynamic complexity

Chaos and predictability

Recommended reading

Exercises and problems

8 Metabolic pathways

Classification and assignment of protein function

The Enzyme Commission

The Gene Ontology Consortium protein function classification

Catalysis by enzymes

Active sites


Protein-ligand binding equilibria

Enzyme kinetics

Measures of effectiveness of enzymes

How do proteins evolve new functions?

Control over enzyme activity

Structural mechanisms of evolution of altered or novel protein functions

Protein evolution at the level of domain assembly

Databases of metabolic pathways


The Kyoto Encyclopedia of Genes and Genomes

Evolution and phylogeny of metabolic pathways

Pathway comparison

Alignment of metabolic pathways

Comparing linear metabolic pathways

Comparing nonlinear metabolic pathways: the pentose phosphate pathway and 
the Calvin–Benson cycle

Dynamics of metabolic networks

Robustness of metabolic networks

Dynamic modeling of metabolism

Recommended reading

Exercises and problems

9 Gene expression and regulation

DNA microarrays

Microarray data are quantitative but imprecise

Analysis of microarray data

Mass spectrometry

Identification of components of a complex mixture

Protein sequencing by mass spectrometry

Measuring deuterium exchange in proteins

Genome sequence analysis by mass spectrometry

Protein complexes and aggregates

Properties of protein-protein complexes

Protein interaction networks

Regulatory networks

Signal transduction and transcriptional control

Structures of regulatory networks

Structural biology of regulatory networks

The genetic switch of bacteriophage λ

What are the characteristics of the switch that must be implemented by DNA–
protein interactions?

The materials

How to ’throw’ the switch

The genetic regulatory network of Saccharomyces cerevisiae

Adaptability of the yeast regulatory network

Recommended reading

Exercises and problems



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