Note that if there are many sequences in the databank that are very similar to the probe sequence, they will head the list. In this case, there are many very similar PAX genes in other mammals. You may have to scan far down the list to find a distant relative that you consider interesting.
In fact, the program has matched only a portion of the sequences. The full alignment is shown in the Box, Complete pairwise sequence alignment of human PAX-6 protein and Drosophila melanogaster eyeless.
See Exercise 1. These appear, embedded in the text of the output, in square brackets; for instance: emb CAA The program makes use of PERL's rich pattern recognition resources to search for character strings of the form [Drosophila melanogaster].
Recall that an associative array is a generalization of an ordinary array or vector, in which the elements are not indexed by integers but by arbitrary strings. A second reference to an associative array with a previously encountered index string may possibly change the value in the array but not the list of index strings In this case we do not care about the value but just use the index strings to compile a unique list of species detected. Multiple references to the same species will merely overwrite the first reference, not make a repetitive list.
Et in terra PAX hominibus, muscisque The eyes of the human, fly and octopus are very different in structure. Conventional wisdom, noting the immense selective advantage conferred by the ability to see, held that eyes arose independently in different phyla. It therefore came as a great surprise that a gene controlling human eye development has a homologue governing eye development in Drosophila.
The PAX-6 gene was first cloned in the mouse and human. It is a master regulatory gene, controlling a complex cascade of events in eye development. Mutations in the human gene cause the clinical condition aniridia, a developmental defect in which the iris of the eye is absent or deformed. The PAX-6 homologue in Drosophila - called the eyeless gene - has a similar function of control over eye development. The Drosophila eyeless mutant was first described in Little did anyone then suspect a relation to a mammalian gene.
Not only are the insect and mammalian genes similar in sequence, they are so closely related that their activity crosses species boundaries. Expression of the mouse PAX-6 gene in the fly causes ectopic eye development just as expression of the fly's own eyeless gene does. PAX-6 has homologues in other phyla, including flatworms, ascidians, sea urchins and nematodes. The observation that rhodopsins - a family of proteins containing retinal as a common chromophore - function as light-sensitive pigments in different phyla is supporting evidence for a common origin of different photoreceptor systems.
The genuine structural differences in the macroscopic anatomy of different eyes reflect the divergence and independent development of higher-order structure. Madden, Alejandro A. Some of the facilities for archiving and retrieving molecular biological information survive this change pretty well intact, some must be substantially altered, and others do not make it at all.
Biochemically, proteins play a variety of roles in life processes: there are structural proteins e. In many cases only a small part of the structure - an active site - is functional, the rest existing only to create and fix the spatial relationship among the active site residues.
Proteins evolve by structural changes produced by mutations in the amino acid sequence. The primary paradigm of evolution is that changes in DNA generate variability in protein structure and function, which affect the reproductive fitness of the individual, on which natural selection acts. Approximately 15 protein structures are now known. From these we have derived our understanding both of the functions of individual proteins - for example, the chemical explanation of catalytic activity of enzymes - and of the general principles of protein structure and folding.
Chemically, protein molecules are long polymers typically containing several thousand atoms, composed of a uniform repetitive backbone or main chain with a particular sidechain attached to each residue see Fig. The amino acid sequence of a protein records the succession of sidechains. The sidechains may be chosen, independently, from the set of 20 standard amino acids. It is the sequence of the sidechains that gives each protein its individual structural and functional characteristics.
The polypeptide chain folds into a curve in space; the course of the chain defining a 'folding pattern'. Proteins show a great variety of folding patterns. Underlying these are a number of common structural features. Folding may be thought of as a kind of intramolecular condensation or crystallization. See Chapter 5. Broken lines indicate H-bonds. The hierarchical nature of protein architecture The Danish protein chemist K.
The assignment of helices and sheets - the hydrogen-bonding pattern of the mainchain - is called the secondary structure. The assembly and interactions of the helices and sheets is called the tertiary structure. For proteins composed of more than one subunit, J. Bernal called the assembly of the monomers the quaternary structure. In some cases, evolution can merge proteins - changing quaternary to tertiary structure. For example, five separate enzymes in the bacterium E. Sometimes homologous monomers form oligomers in different ways; for instance, globins form tetramers in mammalian haemoglobins, and dimers - using a different interface - in the ark clam Scapharca inaequivalvis.
Proteins show recurrent patterns of interaction between helices and sheets close together in the sequence. The chevrons indicate the direction of the chain.
Many proteins contain compact units within the folding pattern of a single chain, that look as if they should have independent stability. These are called domains. Do not confuse domains as substructures of proteins with domains as general classes of living things: archaea, bacteria and eukaryotes. The RNA-binding protein L1 has feature typical of multidomain proteins: the binding site appears in a cleft between the two domains, and the relative geometry of the two domains is flexible, allowing for ligand-induced conformational changes Fig.
In the hierarchy, domains fall between supersecondary structures and the tertiary structure of a complete monomer. Modular proteins are multidomain proteins which often contain many copies of closely related domains. Domains recur in many proteins in different structural contexts; that is, different modular proteins can 'mix and match' sets of domains.
For example, fibronectin, a large extracellular protein involved in cell adhesion and migration, contains 29 domains including multiple tandem repeats of three types of domains called F1, F2, and F3. Fibronectin domains also appear in other modular proteins.
Classification of protein structures The most general classification of families of protein structures is based on the secondary and tertiary structures of proteins.
Among proteins with similar folding patterns, there are families that share enough features of structure, sequence and function to suggest evolutionary relationship. However, unrelated proteins often show similar structural themes. Classification of protein structures occupies a key position in bioinformatics, not least as a bridge between sequence and function. We shall return to this theme, to describe results and relevant web sites.
Meanwhile, the following album of small structures provides opportunities for practicing visual analysis and recognition of the important spatial patterns Fig. Trace the chains visually, picking out helices and sheets. Can you see supersecondary structures? Into which general classes do these structures fall?
See Exercises 1. Protein structure prediction and engineering The amino acid sequence of a protein dictates its three-dimensional structure. When placed in a medium of suitable solvent and temperature conditions, such as provided by a cell interior, proteins fold spontaneously to their native active states. Some proteins require chaperones to fold, but these catalyze the process rather than direct it. This has proved elusive.
In consequence, in addition to pursuing the fundamental problem of a priori prediction of protein structure from amino acid sequence, scientists have defined less-ambitious goals: 1. Secondary structure prediction: Which segments of the sequence form helices and which form strands of sheet? Fold recognition: Given a library of known protein structures and their amino acid sequences, and the amino acid sequence of a protein of unknown structure, can we find the structure in the library that is most likely to have a folding pattern similar to that of the protein of unknown structure?
Homology modelling: Suppose a target protein, of known amino acid sequence but unknown structure, is homologous to one or more proteins of known structure. Then we expect that much of the structure of the target protein will resemble that of the known protein, and it can serve as a basis for a model of the target structure.
The completeness and quality of the result depend crucially on how similar the sequences are. This is a conservative estimate, as the following illustration shows.
Each protein could serve as a good model for the other, at least as far as the course of the mainchain is concerned. To this end, J. Crystallographers and NMR spectroscopists in the process of determining a protein structure are invited to 1 publish the amino acid sequence several months before the expected date of completion of their experiment, and 2 commit themselves to keeping the results secret until an agreed date.
Predictors submit models, which are held until the deadline for release of the experimental structure. Then the predictions and experiments are compared - to the delight of a few and the chagrin of most.
The results of CASP evaluations record progress in the effectiveness of predictions, which has occurred partly because of the growth of the databanks but also because of improvements in the methods. We shall discuss protein structure prediction in Chapter 5. Protein engineering Molecular biologists used to be like astronomers - we could observe our subjects but not modify them.
This is no longer true. In the laboratory we can modify nucleic acids and proteins at will. We can probe them by exhaustive mutation to see the effects on function. We can endow old proteins with new functions, as in the development of catalytic antibodies.
We can even try to create new ones. Many rules about protein structure were derived from observations of natural proteins. These rules do not necessarily apply to engineered proteins. Natural proteins have features required by general principles of physical chemistry, and by the mechanism of protein evolution.
Engineered proteins must obey the laws of physical chemistry but not the constraints of evolution. Engineering of proteins can explore new territory. Even discounting some of the more outrageous claims - hype springs eternal - categories of applications include the following. Diagnosis of disease and disease risks.
DNA sequencing can detect the absence of a particular gene, or a mutation. Identification of specific gene sequences associated with diseases will permit fast and reliable diagnosis of conditions a when a patient presents with symptoms, b in advance of appearance of symptoms, as in tests for inherited late-onset conditions such as Huntington disease see Box , c for in utero diagnosis of potential abnormalities such as cystic fibrosis, and d for genetic counselling of couples contemplating having children.
In many cases our genes do not irrevocably condemn us to contract a disease, but raise the probability that we will. Smoking makes the development of emphysema all but certain. In these cases the disease is brought on by a combination of genetic and environmental factors. Often the relationship between genotype and disease risk is much more difficult to pin down. Some diseases such as asthma depend on interactions of many genes, as well as environmental factors.
In other cases a gene may be all present and correct, but a mutation elsewhere may alter its level of expression or distribution among tissues. Such abnormalities must be detected by measurements of protein activity.
Analysis of protein expression patterns is also an important way to measure response to treatment. Genetics of responses to therapy - customized treatment. Because people differ in their ability to metabolize drugs, different patients with the same condition may require different dosages.
Sequence analysis permits selecting drugs and dosages optimal for individual patients, a fast- growing field called pharmacogenomics. Physicians can thereby avoid experimenting with different therapies, a procedure that is dangerous in terms of side effects - often even fatal - and in any case is expensive.
Treatment of patients for adverse reactions to prescribed drugs consumes billions of dollars in health care costs. Huntington disease 4.
Huntington disease is an inherited neurodegenerative disorder affecting approximately 30 people in the USA. Its symptoms are quite severe, including uncontrollable dance-like choreatic movements, mental disturbance, personality changes, and intellectual impairment.
Death usually follows within 10—15 years after the onset of symptoms. The gene arrived in New England during the colonial period, in the seventeenth century.
It may have been responsible for some accusations of witchcraft. The gene has not been eliminated from the population, because the age of onset - 30—50 years - is after the typical reproductive period. Formerly, members of affected families had no alternative but to face the uncertainty and fear, during youth and early adulthood, of not knowing whether they had inherited the disease.
The discovery of the gene for Huntington disease in made it possible to identify affected individuals. The gene contains expanded repeats of the trinucleotide CAG, corresponding to polyglutamine blocks in the corresponding protein, huntingtin. Huntington disease is one of a family of neurodegenerative conditions resulting from trinucleotide repeats.
The larger the block of CAGs, the earlier the onset and more severe the symptoms. The normal gene contains 11—28 CAG repeats. People with 29—34 repeats are unlikely to develop the disease, and those with 35—41 repeats may develop only relatively mild symptoms. The inheritance is marked by a phenomenon called anticipation: the repeats grow longer in successive generations, progressively increasing the severity of the disease and reducing the age of onset.
For some reason this effect is greater in paternal than in maternal genes. Therefore, even people in the borderline region, who might bear a gene containing 29—41 repeats, should be counselled about the risks to their offspring.
For example, the very toxic drug 6-mercaptopurine is used in the treatment of childhood leukaemia. A small fraction of patients used to die from the treatment, because they lack the enzyme thiopurine methyltransferase, needed to metabolize the drug. Testing of patients for this enzyme identifies those at risk. Conversely, it may become possible to use drugs that are safe and effective in a minority of patients, but which have been rejected before or during clinical trials because of inefficacy or severe side effects in the majority of patients.
Identification of drug targets. A target is a protein the function of which can be selectively modified by interaction by a drug, to affect the symptoms or underlying causes of a disease.
Identification of a target provides the focus for subsequent steps in the drug design process. Among drugs now in use, the targets of about half are receptors, about a quarter enzymes, and about a quarter hormones. The growth in bacterial resistance to antibiotics is creating a crisis in disease control.
There is a very real possibility that our descendants will look back at the second half of the twentieth century as a narrow window during which bacterial infections could be controlled, and before and after which they could not. The urgency of finding new drugs is mitigated by the availability of data on which to base their development.
Genomics can suggest targets. Differential genomics, and comparison of protein expression patterns, between drug-sensitive and resistant strains of pathogenic bacteria can pinpoint the proteins responsible for drug resistance.
The study of genetic variation between tumour and normal cells can, it is hoped, identify differentially expressed proteins as potential targets for anticancer drugs. Gene therapy. If a gene is missing or defective, we would like to replace it or at least supply its product. If a gene is overactive, we would like to turn it off. Direct supply of proteins is possible for many diseases, of which insulin replacement for diabetes and Factor VIII for a common form of haemophilia are perhaps the best known.
Gene transfer has succeeded in animals, for production of human proteins in the milk of sheep and cows. In human patients, gene replacement therapy for cystic fibrosis using adenovirus has shown encouraging results. One approach to blocking genes is called 'antisense therapy'. The idea is to introduce a short stretch of DNA or RNA that binds in a sequence-specific manner to a region of a gene.
Antisense therapy has shown some efficacy against cytomegalovirus and Crohn disease. Antisense therapy is very attractive, because going directly from target sequence to blocker short- circuits many stages of the drug-design process.
The future The new century will see a revolution in healthcare development and delivery. Barriers between 'blue sky' research and clinical practice are tumbling down. It is possible that a reader of this book will discover a cure for a disease that would otherwise kill him or her. One hopes that this happens because the research establishment has succeeded in developing therapeutic or preventative measures against tumours rather than merely by imitating their uncontrolled growth.
Web Resource: For general background: D Casey of Oak Ridge National Laboratory has written two extremely useful compact introductions to molecular biology providing essential background for bioinformatics: Primer on Molecular Genetics Blumberg, B. Includes list of and links to ongoing projects for sequencing of multicellular organisms. Introduction to Protein Structure, 2nd. New York: Garland. Caulfield, T. How many human genome equivalents does this amount to?
How many human genome equivalents will this amount to? Ignore savings available using various kinds of storage compression techniques.
Exercise 1. For which words or phrases would you provide links? We expect that such substitutions would in most cases have relatively little effect on the structure and function of a protein. Name an amino acid that has physicochemical properties very different from d leucine, e aspartic acid, f threonine.
Such substitutions might have severe effects on the structure and function of a protein, especially if they occur in the interior of the protein structure. In Fig. On a photocopy of Fig. Count full lines and half lines. Problem 1. Each line corresponds to the amino acid sequence from one protein, specified as a sequence of letters each specifying one amino acid. Looking down any column shows the amino acids that appear at that position in each of the proteins in the family. In this way patterns of preference are made visible.
For each position containing the same amino acid in every sequence, write the letter symbolizing the common residue in upper case below the column. For each position containing the same amino acid in all but one of the sequences, write the letter symbolizing the preferred residue in lower case below the column.
What patterns of periodicity of conserved residues suggest themselves? What distribution of conservation of charged residues do you observe? Propose a reasonable guess about what kind of molecule these domains interact with. Would it correctly recover: Kate, when France is mine and I am yours, then yours is France and you are mine.
Would it correctly recover: One woman is fair, yet I am well; another is wise, yet I am well; another virtuous, yet I am well; but till all graces be in one woman, one woman shall not come in my grace.
Would it correctly recover: That he is mad, 'tis true: 'tis true 'tis pity; And pity 'tis 'tis true. Warning - this is not an easy problem. Here is an alternative version of the program to assemble overlapping fragments see page 18 :! Anyone who produces code like this should be fired immediately. The absence of comments, and the tricky coding and useless brevity, make it difficult to understand what the program is doing.
A program written in this way is difficult to debug and virtually impossible to maintain. Someday you may succeed someone in a job and be presented with such a program to work on. You will have my sympathy. Photocopy the concise program listed in this problem and the original version on page 18 so that they appear side-by-side on a page. Wherever possible, map each line of the concise program into the corresponding set of lines of the long one.
Prepare a version of the concise program with enough comments to clarify what it is doing for this you could consider adapting the comments from the original program and how it is doing it. Do not change any of the executable statements back to the original version or to anything else ; just add comments.
Weblem 1. Write a one- paragraph explanation of these terms based on these sites. Write the complete taxonomic classification of the organisms from which these are derived. Are the conclusions from the analysis of mitochondrial cytochromes b sequences consistent with those from analysis of the pancreatic ribonucleases?
One hypothesis to explain this observation is that a functional cytochrome b might require so many conserved residues that cytochromes b from all animals are as similar to one another as the elephant and mammoth proteins are.
Test this hypothesis by retrieving cytochrome b sequences from other mammalian species, and check whether the cytochrome b amino acid sequences from more distantly-related species are as similar as the elephant and mammoth sequences. Which pair appears to be the most closely related? Is this surprising to you? Why or why not? This implies, for instance, that he considered crocodiles and salamanders more closely related than crocodiles and birds. Thomas Huxley, on the other hand, in the nineteenth century, grouped reptiles and birds together.
For three suitable proteins with homologues in crocodiles, salamanders and birds, determine the similarity between the homologous sequences. Which pair of animal groups appears most closely related? Who was right, Linnaeus or Huxley? In each case, what protein is administered? What variant carries the highest risk?
What is known about the mechanism by which this variant influences the development of the disease? What is the most common mutation that causes this condition? The cell itself has a diameter of about 0. The DNA of higher organisms is organized into chromosomes - normal human cells contain 23 chromosome pairs. The total amount of genetic information per cell - the sequence of nucleotides of DNA - is very nearly constant for all members of a species, but varies widely between species see Box for longer list : Organism Genome size Epstein- 0.
Conversely, some genes exist in multiple copies. Therefore, the amount of protein sequence information in a cell cannot easily be estimated from the genome size. Genes A single gene coding for a particular protein corresponds to a sequence of nucleotides along one or more regions of a molecule of DNA. The DNA sequence is collinear with the protein sequence.
In species for which the genetic material is double-stranded DNA, genes may appear on either strand. Bacterial genes are continuous regions of DNA. Therefore, the functional unit of genetic sequence information from a bacterium is a string of 3N nucleotides encoding a string of N amino acids, or a string of N nucleotides encoding a structural RNA molecule of N residues. Such a string, equipped with annotations, would form a typical entry in one of the genetic sequence archives.
In eukaryotes the nucleotide sequences that encode the amino acid sequences of individual proteins are organized in a more complex manner. The relationship between size of gene and size of protein encoded is very different from that in bacteria. Frequently one gene appears split into separated segments in the genomic DNA. An intron is an intervening region between two exons.
Cellular machinery splices together the proper segments, in RNA transcripts, based on signal sequences flanking the exons in the sequences themselves. Many introns are very long - in some cases substantially longer than the exons. Psilotum nudum ? Genes may be turned on or off or more finely regulated in response to concentrations of nutrients, or to stress, or to unfold complex programs of development during the lifetime of the organism.
Many control regions of DNA lie near the segments coding for proteins. They contain sequences that serve as binding sites for the molecules that transcribe the DNA sequence, or sequences that bind regulatory molecules that can block transcription.
Simple examples occur in bacterial genomes, in which contiguous genes, coding for several proteins that catalyse successive steps in an integrated sequence of reactions, fall under the control of the same regulatory sequence.
Jacob, J. Monod, and E. Wollman named these operons. One can readily understand the utility of a parallel mechanism for control of their expression. In animals, methylation of DNA provides the signals for tissue-specific expression of developmentally regulated genes. Products of certain genes cause cells to commit suicide - a process called apoptosis.
Defects in the apoptotic mechanism leading to uncontrolled growth are observed in some cancers, and stimulation of these mechanisms is a general approach to cancer therapy.
The conclusion is that to reduce genetic data to individual coding sequences is to disguise the very complex nature of the interrelationships among them, and to ignore the historical and integrative aspects of the genome. Robbins has expressed the situation unimprovably Consider the 3. Obtaining the sequence is equivalent to obtaining an image of the contents of that mass-storage device. Understanding the sequence is equivalent to reverse engineering that unknown computer system both the hardware and the 3.
Furthermore, the files are known to be fragmented. In addition, some of the device contains erased files or other garbage. Once the garbage has been recognized and discarded and the fragmented files reassembled, the reverse engineering of the codes can be undertaken with only a partial, and sometimes incorrect, understanding of the CPU [Central Processing Unit on which the codes run.
In fact, deducing the structure and function of the CPU is part of the project, since some of the 3. In addition, one must also consider that the huge database also contains code generated from the result of literally millions of maintenance revisions performed by the worst possible set of kludge-using, spaghetti-coding, opportunistic hackers who delight in clever tricks like writing self-modifying code and relying upon undocumented system quirks.
Robbins, R. Proteins In principle, a database of amino acid sequences of proteins is inherent in the database of nucleotide sequences of DNA, by virtue of the genetic code. Indeed, new protein sequence data are now being determined by translation of DNA sequences, rather than by direct sequencing of proteins.
Historically, the chemical problem of determining amino acid sequences of proteins directly was solved before the genetic code was established and before methods for determination of nucleotide sequences of DNA were developed. Sanger's sequencing of insulin in first proved that proteins had definite amino acid sequences, a proposition that until then was hypothetical. Should any distinction be made between amino acid sequences determined directly from proteins and those determined by translation from DNA?
First, we must assume that it is possible correctly to identify within the DNA data stream the regions that encode proteins. The pattern-recognition programs that address this question are subject to three types of errors: a genuine protein sequence may be missed entirely, or an incomplete protein may be reported, or a gene may be incorrectly spliced. Several variations on the theme add to the complexity: Genes for different proteins may overlap, or genes may be assembled from exons in different ways in different tissues.
Conversely, some genetic sequences that appear to code for proteins may, in fact, be defective or not expressed. A protein inferred from a genome sequence is a hypothetical object until an experiment verifies its existence. Second, in many cases the expression of a gene produces a molecule that must be modified within a cell, to make a mature protein that differs significantly from the one suggested by translation of the gene sequence. In many cases the missing details of post-translational modifications - the molecular analogues of body piercing - are quite important, and unlike body piercing, have functional significance.
Post-translational modifications include addition of ligands for instance the covalently-bound haem group of cytochrome c , glycosylation, methylation, excision of peptides, and many others. Patterns of disulphide bridges - primary chemical bonds between cysteine residues - cannot be deduced from the amino acid sequence. In some cases, mRNA is edited before translation, creating changes in amino acid sequences that are not inferrable from the genes. Proteomes An organism's genome gives a complete but static set of specifications of the potential life of that individual.
The state of development of the organism, and its activity at the molecular level at any moment, depend primarily on the amounts and distribution of its proteins. The proteome project is a large-scale programme dealing in an integral way with patterns of expression of proteins in biological systems, in ways that complement and extend genome projects. What kinds of data would we like to measure, and what mature experimental techniques exist to determine them?
The basic goal is a spatio-temporal description of the deployment of proteins in the organism. The rates of synthesis of different proteins vary among different tissues and different cell types and states of activity.
Methods are available for efficient analysis of transcription patterns of multiple genes See Box, page 68, and Plate V. However, because proteins 'turn over' at different rates, it is also necessary to measure proteins directly. The distribution of expressed protein levels is a kinetic balance between rates of protein synthesis and degradation. High-resolution two-dimensional polyacrylamide gel electrophoresis 2D PAGE shows the pattern of protein content in a sample.
Mass-spectroscopic techniques identify the proteins into which the sample has been separated, and their post-translational modifications. This figure shows the use of cDNA microarrays to measure the effect of Schistosoma mansoni infection on the transcription profile of genes in mouse liver tissue. Each spot in the arrays reports the activity of a single gene.
Corresponding spots in the two arrays compare the activities of genes in: left uninfected control animals, right 8 week infected animals. Green indicates non-induced expression levels; red indicates induced levels. The goal of such an experiment is to identify patterns in the differentially-expressed genes. In this case, several genes upregulated in reponse to infection indicated in the figure participate in collagen synthesis and deposition. This is associated with a balanced host defense mechanism by which eggs of the parasite are enclosed in a fibrous granuloma.
Study of gene expression patterns linked to the development of this type of lesion can elucidate mechanisms of pathogenesis. It is also possible to make arrays of proteins, to screen for pairs of proteins that interact see Fig. Figure 2. The proteins were produced by individual bacterial clones spotted onto a membrane. Expressed proteins were released by cell lysis. The result was then exposed to a mixture of 12 antibody fragments containing the antigen- combining site , and bound antibody visualized and detected by autoradiography.
Each clone was spotted twice to aid identification of positives; this explains the doublet in the figure. Developments of the method should make possible high-throughput screening for more general types of protein-protein interactions.
From Holt, L. Application of these methods provides a picture of the protein-based activity of an organism, as the genome provides a complete set of potential proteins. Simpson has drawn the analogy: if the genome is a list of the instruments in an orchestra, the proteome is the orchestra in the process of playing a symphony. DNA microarrays can be used 1 to determine expression patterns of different proteins by detection of mRNAs; or 2 for genotyping, by detection of different variant gene sequences, including but not limited to single-nucleotide polymorphisms SNPs.
It is possible to measure simple presence or absence, or to quantitate relative abundance. Note, however, that the correlation between the abundance of an mRNA and of the corresponding protein is imperfect. To determine the expression pattern of all of a cell's genes, it is necessary to measure the relative amounts of many different mRNAs.
Hybridization is an accurate and sensitive way to detect whether a particular sequence is present in a sample of DNA. The key to high-throughput analysis is to run many hybridization experiments in parallel.
This is what microarrays achieve. To achieve parallel hybridization analysis, a large number of DNA oligomers are affixed to known locations on a rigid support, in a regular two-dimensional array. The mixture to be analysed is prepared with radioactive or fluorescent tags, to permit detection of hybrids.
After the array is exposed to the mixture, each element of the array to which some component of the mixture has become attached bears the radioactive or fluorescent tag.
Because we know the sequence of the oligomeric probe at any position of the array, measurement of the positions of the probes identifies their sequences. Introduction 2.
From genetics to genomes 3. The panorama of life 4. Alignments and Phylogenetic Trees 5. Structural bioinformatics and drug discovery 6.
Scientific publications and archives: media, content, access, and presentation 7. Artificial intelligence and machine learning 8.
Introduction to systems biology 9. Metabolic pathways Control of organization and organization of control. Oxford University Press is a department of the University of Oxford. It furthers the University's objective of excellence in research, scholarship, and education by publishing worldwide. Academic Skip to main content. Introduction to Bioinformatics Arthur Lesk Limited preview — Furthermore, frequent examples, self-test questions, problems, and exercises are incorporated throughout the text to encourage self-directed learning.
This text describes how bioinformatics can be used as a powerful Introduction to Bioinformatics Arthur M. Fully revised and updated, the fourth edition of Introduction to Bioinformatics shows how bioinformatics can be used as a powerful set of tools for retrieving and analyzing this biological data, and how bioinformatics can be applied to a wide range of disciplines such as molecular biology, medicine, biotechnology, forensic science, and anthropology.
Selected pages Title Page. Additionally, frequent examples, self-test questions, problems, and exercises are incorporated throughout the text to encourage self-directed learning. Oxford University Press is a department of the University of Oxford. The Online Resource Center includes data sets and Web-based problems, alongside guidance for answering the problems and exercises in the book.
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