Biological Sequence Analysis: Probabilistic Models of Proteins and Nucleic Acids (Paperback)

by Richard Durbin (Author), Sean R. Eddy (Author), Anders Krogh (Author), Graeme Mitchison (Author) "Astronomy began when the Babylonians mapped the heavens..." (more)
Key Phrases: standard pairwise alignment, full probabilistic model, traceback algorithm (more...)

Editorial Reviews

Review
"The book is amply illustrated with biological applications and examples." Cell

"...successfully integrates numerous probabilistic models with computational algorithms to solve molecular biology problems of sequence alignment...an excellent textbook selection for a course on bioinformatics and a very useful consultation book for a mathematician, statistician, or biometrician working in sequence alignment." Bulletin of Mathematical Biology

"This is one of the more rewarding books I have read within this field. My overall evaluation is that this book is very good and a must read for active participants in the field. In addition, it could be particularly useful for molecular biologists" Theoretical Population Biology

Product Description
Probablistic models are becoming increasingly important in analyzing the huge amount of data being produced by large-scale DNA-sequencing efforts such as the Human Genome Project. For example, hidden Markov models are used for analyzing biological sequences, linguistic-grammar-based probabilistic models for identifying RNA secondary structure, and probabilistic evolutionary models for inferring phylogenies of sequences from different organisms. This book gives a unified, up-to-date and self-contained account, with a Bayesian slant, of such methods, and more generally to probabilistic methods of sequence analysis. Written by an interdisciplinary team of authors, it is accessible to molecular biologists, computer scientists, and mathematicians with no formal knowledge of the other fields, and at the same time presents the state of the art in this new and important field.

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Product Details

• Paperback: 356 pages
• Publisher: Cambridge University Press (July 1, 1999)
• Language: English
• ISBN-10: 0521629713
• ISBN-13: 978-0521629713
• Product Dimensions: 9.6 x 6.8 x 0.8 inches
• Shipping Weight: 1.5 pounds (View shipping rates and policies)
• Average Customer Review: 4.5 out of 5 stars See all reviews (19 customer reviews)
• Amazon.com Sales Rank: #256,059 in Books (See Bestsellers in Books)

Customer Reviews

Most Helpful Customer Reviews

33 of 35 people found the following review helpful:

5.0 out of 5 stars Excellent overview of probabilistic computational biology, April 1, 2001

By	Dr. Lee D. Carlson (Baltimore, Maryland USA) - See all my reviews (TOP 100 REVIEWER)    (REAL NAME)

This book is a very well written overview to hidden Markov models and context-free grammar methods in computational biology. The authors have written a book that is useful to both biologists and mathematicians. Biologists with a background in probability theory equivalent to a senior-level course should be able to follow along without any trouble. The approach the author's take in the book is very intuitive and they motivate the concepts with elementary examples before moving on to the more abstract definitions. Exercises also abound in the book, and they are straightforward enough to work out, and should be if one desires an in-depth understanding of the main text. In addition, there is a software package called HMMER, developed by one of the authors (Eddy) that is in the public domain and can be downloaded from the Internet. The package specifically uses hidden Markov models to perform sequence analysis using the methods outlined in the book.

Probabilistic modeling has been applied to many different areas, including speech recognition, network performance analysis, and computational radiology. An overview of probabilistic modeling is given in the first chapter, and the authors effectively introduce the concepts without heavy abstract formalism, which for completeness they delegate to the last chapter of the book. Bayesian parameter estimation is introduced as well as maximum likelihood estimation. The authors take a pragmatic attitude in the utility of these different approaches, with both being developed in the book.

This is followed by a treatment of pairwise alignment in Chapter Two, which begins with substitution matrices. They point out, via some exercises, the role of physics in influencing particular alignments (hydrophobicity for example). Global alignment via the Gotoh algorithm and local alignment via the Smith-Waterman algorithm, are both discussed very effectively. Finite state machines with accompanying diagrams are used to discuss dynamic programming approaches to sequence alignment. The BLAST and FASTA packages are briefly discussed, along with the PAM and BLOSUM matrices.

Hidden Markov models are treated thoroughly in the next chapter with the Viterbi and Baum-Welch algorithms playing the central role. HIdden Markov models are then used in Chapter 4 for pairwise alignment. State diagrams are again used very effectively to illustrate the relevant ideas. Profile hidden Markov models which, according to the authors are the most popular application of hidden Markov models, are treated in detail in the next chapter. A very surprising application of Voronoi diagrams from computational geometry to weighting training sequences is given.

Several different approaches, such as Barton-Sternberg, CLUSTALW, Feng-Doolittle, MSA, simulated annealing, and Gibbs sampling are applied to multiple sequence alignment methods in Chapter 6. It is very well written, with the only disappointment being that only one exercise is given in the entire chapter. Phylogenetic trees are covered in Chapter 7, with emphasis placed on tree building algorithms using parsimony. The next chapter discusses the same topic from a probabilistic perspective. This to me was the most interesting part of the book as it connects the sequence alignment algorithms with evolutionary models.

The authors switch gears starting with the next chapter on transformational grammars. It is intriguing to see how concepts used in compiler construction can be generalized to the probabilistic case and then applied to computational biology. The PROSITE database is given as an example of the application of regular grammars to sequence matching. This chapter is fascinating reading, and there are some straightforward exercises illustrating the main points.

The last chapter covers RNA structure analysis, which introduces the concept of a pseudoknot. These are not to be confused with the usual knot constructions that can be applied to the topology of DNA, but instead result from the existence of non-nested base pairs in RNA sequences. The authors discuss many other techniques used in RNA sequence analysis and take care to point out which ones are more practical from a computational point of view. Surprisingly, genetic algorithms and algorithms based on Monte Carlo sampling are not discussed in the book, but the authors do give references for the interested reader.

The best attribute of this book is that the authors take a pragmatic point of view of how mathematics can be applied to problems in computational biology. They are not dogmatic about any particular approach, but instead fit the algorithm to the problem at hand.

18 of 19 people found the following review helpful:

5.0 out of 5 stars Fantastic Descriptions of Probabilistic Sequence Algorithms, April 28, 2002

By	Bob Carpenter (New York, NY) - See all my reviews

I picked up this book at the recommendation of a number of colleagues in computational linguistics and speech processing as a way to find out what's going on in biological sequence analysis. I was hoping to learn about applications of the kinds of algorithms I know for handling speech and language, such as HMM decoding and context-free grammar parsing, to biological sequences. This book delivered, as recommended.

As the title implies, "Biological Sequence Analysis" focuses almost exlusively on sequence analysis. After a brief overview of statistics (more a reminder than an introduction), the first half of the book is devoted to alignment algorithms. These algorithms take pairs of sequences of bases making up DNA or sequences of amino acids making up proteins and provide optimal alignments of the sequences or of subsequences according to various statistical models of match likelihoods. Methods analyzed include edit distances with various substitution and gapping penalties (penalties for sections that don't match), Hidden Markov Models (HMMs) for alignment and also for classification against families, and finally, multiple sequence alignment, where alignment is generalized from pairs to sets of sequences. I found the section on building phylogenetic trees by means of hierarchical clustering to be the most fascinating section of the book (especially given its practical application to classifying wine varietals!). The remainder of the book is devoted to higher-order grammars such as context-free grammars, and their stochastic generalization. Stochastic context-free grammars are applied to the analysis of RNA secondary structure (folding). There is a good discussion of the CYK dynamic programming algorithm for non-deterministic context-free grammar parsing; an algorithm that is easily applied to finding the best parse in a probabilistic grammar. The presentations of the dynamic programming algorithms for HMM decoding, edit distance minimization, hierarchical clustering and context-free grammar parsing are as good as I've seen anywhere. They are precise, insightful, and informative without being overly subscripted. The illustrations provided are extremely helpful, including their positioning on pages where they're relevant.

This book is aimed at biologists trying to learn about algorithms, which is clear from the terse descriptions of the underlying biological problems. The technical details were so clear, though, that I was able to easily follow the algorithms even if I wasn't always sure about the genetic applications. After studying some introductions to genetics and coming back to this book, I was able to follow the application discussions much more easily. This book assumes the reader is familiar with algorithms and is comfortable manipulating a lot of statistics; a gentler introduction to exactly the same mathematics and algorithms can be found in Jurafsky and Martin's "Speech and Language Processing". For biologists who want to see how sequence statistics and algorithms applied to language, I would suggest Manning and Schuetze's "Foundations of Statistical Natural Language Processing". Although it is much more demanding computationally, more details on all of these algorithms, as well as some more background on the biology, along with some really nifty complexity analysis can be found in Dan Gusfield's "Algorithms on Strings, Trees and Sequences".

In these days of fly-by-night copy-editing and typesetting, I really appreciate Cambridge University Press's elegant style and attention to detail. Durbin, Eddy, Krogh and Mitchison's "Biological Sequence Analysis" is as beautiful and readable as it is useful.

13 of 14 people found the following review helpful:

4.0 out of 5 stars Best practical introduction, April 17, 2001

By	"bioinformatician" (Oakland, CA United States) - See all my reviews

This is the best introduction to latest probabilistic sequence analysis methods. However, the book suffers from somewhat convoluted writing and organization. More importantly, it lacks a broader theoretical overview of the different methods. The methods are presented as a bunch of tools without enough critical assessment of their effectiveness or the relative strengths of their underlying theoretical models. I would have welcomed more discussion of how they all fit in a bigger probabilistic picture... what are the different simplifications and assumptions made for the sake of simplicity and computation?