Computational biology / bioinformatics Books

Book SynopsisPraise for the First Edition extremely well writtena comprehensive and up-to-date overview of this important field. Journal of Environmental Quality Exploration and Analysis of DNA Microarray and Other High-Dimensional Data, Second Edition provides comprehensive coverage of recent advancements in microarray data analysis. A cutting-edge guide, the Second Edition demonstrates various methodologies for analyzing data in biomedical research and offers an overview of the modern techniques used in microarray technology to study patterns of gene activity. The new edition answers the need for an efficient outline of all phases of this revolutionary analytical technique, from preprocessing to the analysis stage. Utilizing research and experience from highly-qualified authors in fields of data analysis, Exploration and Analysis of DNA Microarray and Other High-Dimensional Data, Second Edition featurTrade Review“Featuring new information on interpretation of findings, class prediction, ABC clustering, limma for mixed models, biclustering, mass spectrometry, tracking Spearman correlations, and more, this \extremely well written" (Journal of Environmental Quality) book is a choice reference for scientists, teachers, and students interested in DNA data analysis.” (Zentralblatt MATH, 1 October 2014) “In summary this is an excellent text for both life scientist and computer/mathematicians. Highly recommended.” (Scientific Computing, 1 August 2014) Table of ContentsPreface xv Acknowledgments xvii 1 A brief introduction 1 1.1 A note on exploratory data analysis 3 1.2 Computing considerations and software 4 1.3 A brief outline of the book 5 1.4 Datasets and case studies 7 2 Genomics basics 11 2.1 Genes 11 2.2 DNA 12 2.3 Gene expression 13 2.4 Hybridization assays and other laboratory techniques 15 2.5 The human genome 16 2.6 Genome variations and their consequences 18 2.7 Genomics 19 2.8 The role of genomics in pharmaceutical and research and clinical practice 20 2.9 Proteins 23 2.10 Bioinformatics 23 3 Microarrays 27 3.1 Types of microarray experiments 28 3.2 A very simple hypothetical microarray experiment 32 3.3 A typical microarray experiment 34 3.4 Multichannel cDNA microarrays 38 3.5 Oligonucleotide microarrays 38 3.6 Bead based arrays 40 3.7 Confirmation of microarray results 40 4 Processing the scanned image 43 4.1 Converting the scanned image to the spotted image 44 4.2 Quality assessment 47 4.3 Adjusting for background 53 4.4 Expression level calculation for twochannel cDNA microarrays 56 4.5 Expression level calculation for oligonucleotide microarrays 58 5 Preprocessing microarray data 65 5.1 Logarithmic transformation 66 5.2 Variance stabilizing transformations 66 5.3 Sources of bias 68 5.4 Normalization 69 5.5 Intensity dependent normalization 70 5.6 Judging the success of a normalization 81 5.7 Outlier identification 83 5.8 Nonresistant rules for outlier identification 83 5.9 Resistant rules for outlier identification 83 5.10 Assessing replicate array quality 84 6 Summarization 95 6.1 Replication 95 6.2 Technical replicates 96 6.3 Biological replicates 100 6.4 Biological replicates 100 6.5 Multiple oligonucleotide arrays 102 6.6 Estimating fold change in twochannel experiments 104 6.7 Bayes estimation of fold change 105 6.8 Estimating fold change Affymetrix data 106 6.9 RMA Summarization of multiple oligonucleotide arrays revisited 107 6.10 FARMS summarization. 108 7 Two group comparative experiments 119 7.1 Basics of statistical hypothesis testing 120 7.2 Fold changes 123 7.3 The two sample t test 123 7.4 Diagnostic checks 127 7.5 Robust t tests 129 7.6 The Mann Whitney Wilcox on rank sum test 130 7.7 Multiplicity 132 7.8 The false discovery rate 135 7.9 Resampling based Multiple Testing Procedures 138 7.10 Small variance adjusted t tests and SAM 140 7.11 Conditional t 146 7.12 Borrowing strength across genes 149 7.13 Twochannel experiments 151 7.14 Filtering 153 8 Model based inference and experimental design considerations 177 8.1 The F test 178 8.2 The basic linear model 179 8.3 Fitting the model in two stages 181 8.4 Multichannel experiments 182 8.5 Experimental design considerations 183 8.6 Miscellaneous issues 187 8.7 Model based analysis of Affymetrix arrays 188 9 Analysis of gene sets 211 9.1 Methods for identifying enriched gene sets 213 9.2 ORA and Fisher’s exact test 217 9.3 Interpretation of results 217 9.4 Example 217 10 Pattern discovery 221 10.1 Initial considerations 222 10.2 Cluster analysis 223 10.3 Seeking patterns visually 241 10.4 Biclustering 254 11 Class prediction 263 11.1 Initial considerations 264 11.2 Linear Discriminant Analysis 269 11.3 Extensions of Fisher’s LDA 275 11.4 Penalized methods 278 11.5 Nearest neighbors 279 11.6 Recursive partitioning 280 11.7 Ensemble methods 285 11.8 Enriched ensemble classifiers 288 11.9 Neural networks 288 11.10 Support Vector Machines 289 11.11 Generalized enriched methods 291 11.12 Integration of genome information 301 12 Protein arrays 307 12.1 Introduction 307 12.2 Protein array experiments 308 12.3 Special issues with protein arrays 310 12.4 Analysis 310 12.5 Using antibody antigen arrays to measure protein concentrations 311 References 317 Index 337

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Book SynopsisWritten by an international team of experts, Somatic Genome Variation presents a timely summary of the latest understanding of somatic genome development and variation in plants, animals, and microorganisms.Table of ContentsList of Contributors xv Preface and Introduction xix Acknowledgments xxi About the Editor xxiii Part I Somatic Genome Variation in Animals and Humans 1 1 Polyploidy in Animal Development and Disease 3Jennifer L. Bandura and Norman Zielke 1.1 Introduction 3 1.2 Mechanisms Inducing Somatic Polyploidy 4 1.3 The Core Cell Cycle Machinery 8 1.4 Genomic Organization of Polyploid Cells 9 1.5 Endoreplication: An Effective Tool for Post-Mitotic Growth and Tissue Regeneration 10 1.6 Initiation of Endoreplication in Drosophila 11 1.7 Mechanisms of Endocycle Oscillations in Drosophila 15 1.8 Gene Amplification in Drosophila Follicle Cells 17 1.9 Endocycle Entry in the Trophoblast Lineage 19 1.10 Mechanisms of Endocycle Oscillations in Trophoblast Giant Cells 22 1.11 Cardiomyocytes 23 1.12 Hepatocytes 25 1.13 Megakaryocytes 28 1.14 Concluding Remarks 30 Acknowledgments 31 References 31 2 Large-Scale Programmed Genome Rearrangements in Vertebrates 45Jeramiah J. Smith 2.1 Introduction 45 2.1 Hagfish 46 2.3 Sea Lamprey 48 2.4 Zebra Finch 48 2.5 Emerging Themes and Directions 49 References 51 3 Chromosome Instability in Stem Cells 55Paola Rebuzzini, Maurizio Zuccotti, Carlo Alberto Redi and Silvia Garagna 3.1 Introduction 55 3.2 Pluripotent Stem Cells 56 3.3 Somatic Stem Cells 58 3.4 Mechanisms of Chromosomal Instability 59 3.5 Mechanisms of Chromosomal Instability in Stem Cells 63 References 63 Part II Somatic Genome Variation in Plants 75 4 Mechanisms of Induced Inheritable Genome Variation in Flax 77Christopher A. Cullis 4.1 Introduction 77 4.2 Restructuring the Flax Genome 79 4.3 Specific Genomic Changes 80 4.4 What Happens When Plastic Plants Respond to Environmental Stresses? 83 4.5 When Do the Genomic Changes Occur and Are they Adaptive? 83 4.6 Is this Genomic Response of Flax Unique? 84 4.7 Concluding Remarks 87 Acknowledgments 87 References 87 5 Environmentally Induced Genome Instability and its Inheritance 91Andrey Golubov 5.1 Introduction 91 5.2 Stress and its Effects on Genomes 92 5.3 Transgenerational Inheritance 96 5.4 Concluding Remarks 97 Acknowledgments 97 References 97 6 The Mitochondrial Genome, Genomic Shifting, and Genomic Conflict 103Gregory G. Brown 6.1 Introduction 103 6.2 Heteroplasmy and Sublimons 105 6.3 Cytoplasmic Male Sterility (CMS) in Plants 108 6.4 Mitochondrial Sublimons and CMS 109 6.5 Restorer Gene Evolution: Somatic Genetic Changes Drive Nuclear Gene Diversity? 111 6.6 Concluding Remarks 112 References 113 7 Plastid Genome Stability and Repair 119Éric Zampini, Sébastien Truche, Étienne Lepage, Samuel Tremblay]Belzile and Normand Brisson 7.1 Introduction 120 7.2 Characteristics of the Plastid Genome 121 7.3 Replication of Plastid DNA 124 7.4 Transcription in the Plastid 130 7.5 The Influence of Replication and Transcription on Plastid Genome Stability 131 7.6 Plastid Genome Stability and DNA Repair 133 7.7 Outcomes of DNA Rearrangements 145 7.8 Concluding Remarks 147 References 148 Part III Somatic Genome Variation in Microorganisms 165 8 RNA-Mediated Somatic Genome Rearrangement in Ciliates 167John R. Bracht 8.1 Introduction 168 8.2 Ciliates: Ubiquitous Eukaryotic Microorganisms with a Long Scientific History 168 8.3 Two’s Company: Nuclear Dimorphism in Ciliates 170 8.4 Paramecium: Non-Mendelian Inheritance Comes to Light 171 8.5 Tetrahymena and the Origin of the scanRNA Model 173 8.6 Small RNAs in Stylonychia and Oxytricha 175 8.7 Long Noncoding RNA Templates in Genome Rearrangement 176 8.8 Long Noncoding RNA: An Interface for Short Noncoding RNA 177 8.9 Short RNA-Mediated Heterochromatin Formation and DNA Elimination 179 8.10 Transposable Elements and the Origins of Genome Rearrangements 182 8.11 Transposons, Phase Variation, and Programmed Genome Engineering in Bacteria 185 8.12 Transposases, Noncoding RNA, and Chromatin Modifications in VDJ Recombination of Vertebrates 186 8.13 Concluding Remarks: Ubiquitous Genome Variation, Transposons, and Noncoding RNA 187 Acknowledgments 187 References 187 9 Mitotic Genome Variations in Yeast and Other Fungi 199Adrianna Skoneczna and Marek Skoneczny 9.1 Introduction 199 9.2 The Replication Process as a Possible Source of Genome Instability 200 9.3 Post-Replicative Repair (PRR) or Homologous Recombination (HR) Are Responsible for Error-Free and Error-Prone Repair of Blocking Lesions and Replication Stall-Borne Problems 219 9.4 Ploidy Maintenance and Chromosome Integrity Mechanisms 229 9.5 Concluding Remarks 234 References 235 Part IV General Genome Biology 251 10 Genome Variation in Archaeans, Bacteria, and Asexually Reproducing Eukaryotes 253Xiu-Qing Li 10.1 Introduction 254 10.2 Chromosome Number in Prokaryote Species 254 10.3 Genome Size Variation in Archaeans and Bacteria 255 10.4 Archaeal and Bacterial Genome Size Distribution 256 10.5 Genomic GC Content in Archaeans, Bacteria, Fungi, Protists, Plants, and Animals 257 10.6 Correlation between GC Content and Genome or Chromosome Size 259 10.7 Genome Size and GC-Content Variation in Primarily Asexually Reproducing Fungi 260 10.8 Variation of Gene Direction 263 10.9 Concluding Remarks 263 Acknowledgments 264 References 264 11 RNA Polyadenylation Site Regions: Highly Similar in Base Composition Pattern but Diverse in Sequence—A Combination Ensuring Similar Function but Avoiding Repetitive-Regions-Related Genomic Instability 267Xiu-Qing Li and Donglei Du 11.1 General Introduction to Gene Number, Direction, and RNA Polyadenylation 268 11.2 Base Selection at the Poly(A) Tail Starting Position 269 11.3 Most Frequent Upstream Motifs in Microorganisms, Plants, and Animals 271 11.4 Motif Frequencies in the Whole Genome 273 11.5 The Top 20 Hexamer Motifs in the Poly(A) Site Region in Humans 273 11.6 Polyadenylation Signal Motif Distribution 273 11.7 Alternative Polyadenylation 275 11.8 Base Composition of 3′UTR in Plants and Animals 276 11.9 Base Composition Comparison between 3′UTR and Whole Genome 276 11.10 Base Composition of 3′COR in Plants and Animals 277 11.11 Base Composition Pattern of the Poly(A) Site Region in Protists 278 11.12 Base Composition Pattern of the Poly(A) Site Region in Plants 280 11.13 Base Composition Pattern of the Poly(A) Site Region in Animals 280 11.14 Comparison of Poly(A) Site Region Base Composition Patterns in Plants and Animals 280 11.15 Common U-A-U-A-U Base Abundance Pattern in the Poly(A) Site Region in Fungi, Plants, and Animals 284 11.16 Difference between the Most Frequent Motifs and Seqlogo-Showed Most Frequent Bases 284 11.17 RNA Structure of the Poly(A) Site Region 286 11.18 Low Conservation in the Overall Nucleotide Sequence of the Poly(A) Site Region 286 11.19 Poly(A) Site Region Stability and Somatic Genome Variation 286 11.20 Concluding Remarks 287 Acknowledgments 288 References 288 12 Insulin Signaling Pathways in Humans and Plants 291Xiu]Qing Li and Tim Xing 12.1 Introduction 291 12.2 Ranking of the Insulin Signaling Pathway and its Key Proteins 293 12.3 Diseases Caused by Somatic Mutations of the PI3K, PTEN, and AKT Proteins in the Insulin Signaling Pathway 293 12.4 Plant Insulin and Medical Use 295 12.5 Role of the Insulin Signaling Pathway in Regulating Plant Growth 295 12.6 Concluding Remarks 295 References 296 13 Developmental Variation in the Nuclear Genome Primary Sequence 299Xiu-Qing Li 13.1 Introduction 299 13.2 Genetic Mutation, DNA Damage and Protection, and Gene Conversion in Somatic Cells 300 13.3 Programmed Large-Scale Variation in Primary DNA Sequences in Somatic Nuclear Genome 302 13.4 Generation of Antibody Genes in Animals through Somatic Genome Variation 303 13.5 Developmental Variation in Primary DNA Sequences in the Somatic Cells of Plants 303 13.6 Heritability and Stability of Developmentally Induced Variation in the Somatic Nuclear Genome in Plants 303 13.7 Concluding Remarks 304 References 305 14 Ploidy Variation of the Nuclear, Chloroplast, and Mitochondrial Genomes in Somatic Cells 309Xiu]Qing Li, Benoit Bizimungu, Guodong Zhang and Huaijun Si 14.1 Introduction 310 14.2 Nuclear Genome in Somatic Cells 311 14.3 Plastid Genome Variation in Somatic Cells 317 14.4 Mitochondrial Genome in Somatic Cells 320 14.5 Organelle Genomes in Somatic Hybrids 324 14.6 Effects of Nuclear Genome Ploidy on Organelle Genomes 325 14.7 Concluding Remarks 326 Acknowledgments 326 References 326 15 Molecular Mechanisms of Somatic Genome Variation 337Xiu-Qing Li 15.1 Introduction 338 15.2 Mutation of Genes Involved in the Cell Cycle, Cell Division, or Centromere Function 338 15.3 DNA Damage 338 15.4 Variation in Induction and Activity of Radical-Scavenging Enzymes 339 15.5 DNA Cytosine Deaminases 340 15.6 Variation in Protective Roles of Pigments against Oxidative Damage 340 15.7 RNA-Templated DNA Repair 341 15.8 Errors in DNA Repair 341 15.9 RNA-Mediated Somatic Genome Rearrangement 342 15.10 Repetitive DNA Instability 342 15.11 Extracellular DNA 343 15.12 DNA Transposition 343 15.13 Somatic Crossover and Gene Conversion 343 15.14 Molecular Heterosis 344 15.15 Genome Damage Induced by Endoplasmic Reticulum Stress 344 15.16 Telomere Degeneration 344 15.17 Concluding Remarks 344 References 345 16 Hypotheses for Interpreting Somatic Genome Variation 351Xiu-Qing Li 16.1 Introduction 352 16.2 Cell-Specific Accumulation of Somatic Genome Variation in Somatic Cells 352 16.3 Developmental Age and Genomic Network of Reproductive Cells 353 16.4 Genome Generation Cycle of Species 353 16.5 Somatic Genome Variation and Tissue-Specific Requirements during Growth or Development 354 16.6 Costs and Benefits of Somatic Genome Variation 354 16.7 Hypothesis on the Existence of a Primitive Stage in both Animals and Plants 355 16.8 Sources of Genetic Variation from in Vitro Culture Propagation 357 16.9 Hypothesis that Heterosis Is Created by Somatic Genome Variation 357 16.10 Genome Stability through Structural Similarity and Sequence Dissimilarity 358 16.11 Hypothesis Interpreting the Maternal Transmission of Organelles 358 16.12 Ability of Humans to Deal with Somatic Genome Variation and Diseases 359 16.13 Concluding Remarks 360 References 360 17 Impacts of Somatic Genome Variation on Genetic Theories and Breeding Concepts, and the Distinction between Mendelian Genetic Variation, Somagenetic Variation, and Epigenetic Variation 363Xiu]Qing Li 17.1 Introduction 364 17.2 The Term ‘Somatic Genome’ 365 17.3 Mendelian Genetic Variation, Epigenetic Variation, and Somagenetic Variation 365 17.4 What Is a Gene? 367 17.5 Breeding Criteria, Genome Cycle, Pure Lines, and Variety Stability 368 17.6 The Weismann Barrier Hypothesis and the Need for Revision 370 17.7 Implications for Species Evolution 370 17.8 Concluding Remarks 371 References 372 18 Somatic Genome Variation: What it Is and What it Means for Agriculture and Human Health 377Xiu-Qing Li 18.1 Introduction 378 18.2 Natural Attributes of Somatic Genome Variation 378 18.3 Implications of Somatic Genome Variation for Human and Animal Health 380 18.4 Implications of Somatic Genome Variation for Agriculture 385 18.5 Concluding Remarks 391 Acknowledgments 392 References 392 Index 405

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Book SynopsisPlant Genes, Genomes and Genetics provides a comprehensive treatment of all aspects of plant gene expression. Unique in explaining the subject from a plant perspective, it highlights the importance of key processes, many first discovered in plants, that impact how plants develop and interact with the environment.Table of ContentsAcknowledgements xi Introduction xiii About the Companion Website xix PART I: PLANT GENOMES AND GENES Chapter 1 Plant genetic material 3 1.1 DNA is the genetic material of all living organisms, including plants 3 1.2 The plant cell contains three independent genomes 8 1.3 A gene is a complete set of instructions for building an RNA molecule 10 1.4 Genes include coding sequences and regulatory sequences 11 1.5 Nuclear genome size in plants is variable but the numbers of protein-coding, non-transposable element genes are roughly the same 12 1.6 Genomic DNA is packaged in chromosomes 15 1.7 Summary 15 1.8 Problems 15 References 16 Chapter 2 The shifting genomic landscape 17 2.1 The genomes of individual plants can differ in many ways 17 2.2 Differences in sequences between plants provide clues about gene function 20 2.3 SNPs and lengthmutations in simple sequence repeats are useful tools for genome mapping and marker assisted selection 22 2.4 Genome size and chromosome number are variable 28 2.5 Segments of DNA are often duplicated and can recombine 30 2.6 Some genes are copied nearby in the genome 31 2.7 Whole genome duplications are common in plants 34 2.8 Whole genome duplication has many effects on the genome and on gene function 37 2.9 Summary 41 2.10 Problems 42 Further reading 42 References 42 Chapter 3 Transposable elements 45 3.1 Transposable elements are common in genomes of all organisms 45 3.2 Retrotransposons are mainly responsible for increases in genome size 46 3.3 DNA transposons create small mutations when they insert and excise 52 3.4 Transposable elements move genes and change their regulation 57 3.5 How are transposable elements controlled? 60 3.6 Summary 60 3.7 Problems 61 References 61 Chapter 4 Chromatin, centromeres and telomeres 63 4.1 Chromosomes are made up of chromatin, a complex of DNA and protein 63 4.2 Telomeres make up the ends of chromosomes 67 4.3 The chromosome middles–centromeres 71 4.4 Summary 77 4.5 Problems 77 Further reading 77 References 77 Chapter 5 Genomes of organelles 79 5.1 Plastids and mitochondria are descendants of free-living bacteria 79 5.2 Organellar genes have been transferred to the nuclear genome 80 5.3 Organellar genes sometimes include introns 82 5.4 Organellar mRNA is often edited 82 5.5 Mitochondrial genomes contain fewer genes than chloroplasts 84 5.6 Plant mitochondrial genomes are large and undergo frequent recombination 87 5.7 All plastid genomes in a cell are identical 91 5.8 Plastid genomes are similar among land plants but contain some structural rearrangements 93 5.9 Summary 95 5.10 Problems 95 Further reading 95 References 95 PART II: TRANSCRIBING PLANT GENES Chapter 6 RNA 99 6.1 RNA links components of the Central Dogma 99 6.2 Structure provides RNA with unique properties 102 6.3 RNA has multiple regulatory activities 105 6.4 Summary 108 6.5 Problems 108 References 109 Chapter 7 The plant RNA polymerases 111 7.1 Transcription makes RNA from DNA 111 7.2 Varying numbers of RNA polymerases in the different kingdoms 112 7.3 RNA polymerase I transcribes rRNAs 114 7.4 RNA polymerase III recruitment to upstream and internal promoters 116 7.5 Plant-specific RNP-IV and RNP-V participate in transcriptional gene silencing 117 7.6 Organelles have their own set of RNA polymerases 117 7.7 Summary 118 7.8 Problems 118 References 118 Chapter 8 Making mRNAs – Control of transcription by RNA polymerase II 121 8.1 RNA polymerase II transcribes protein-coding genes 121 8.2 The structure of RNA polymerase II reveals how it functions 121 8.3 The core promoter 123 8.4 Initiation of transcription 125 8.5 The mediator complex 127 8.6 Transcription elongation: the role of RNP-II phosphorylation 128 8.7 RNP-II pausing and termination 129 8.8 Transcription re-initiation 130 8.9 Summary 130 8.10 Problems 130 References 130 Chapter 9 Transcription factors interpret cis-regulatory information 133 9.1 Information on when, where and how much a gene is expressed is codified by the gene’s regulatory regions 133 9.2 Identifying regulatory regions requires the use of reporter genes 134 9.3 Gene regulatory regions have a modular structure 135 9.4 Enhancers: Cis-regulatory elements or modules that function at a distance 137 9.5 Transcription factors interpret the gene regulatory code 138 9.6 Transcription factors can be classified in families 138 9.7 How transcription factors bind DNA 139 9.8 Modular structure of transcription factors 143 9.9 Organization of transcription factors into gene regulatory grids and networks 146 9.10 Summary 146 9.11 Problems 146 More challenging problems 147 References 147 Chapter 10 Control of transcription factor activity 149 10.1 Transcription factor phosphorylation 149 10.2 Protein–protein interactions 151 10.3 Preventing transcription factors from access to the nucleus 155 10.4 Movement of transcription factors between cells 156 10.5 Summary 158 10.6 Problems 158 References 158 Chapter 11 Small RNAs 161 11.1 The phenomenon of cosuppression or gene silencing 161 11.2 Discovery of small RNAs 162 11.3 Pathways for miRNA formation and function 163 11.4 Plant siRNAs originate from different types of double-stranded RNAs 166 11.5 Intercellular and systemic movement of small RNAs 168 11.6 Role of miRNAs in plant physiology and development 170 11.7 Summary 171 11.8 Problems 171 References 172 Chapter 12 Chromatin and gene expression 173 12.1 Packing long DNA molecules in a small space: the function of chromatin 173 12.2 Heterochromatin and euchromatin 173 12.3 Histone modifications 174 12.4 Histone modifications affect gene expression 175 12.5 Introducing and removing histone marks: writers and erasers 175 12.6 ‘Readers’ recognize histone modifications 177 12.7 Nucleosome positioning 177 12.8 DNA methylation 178 12.9 RNA-directed DNA methylation 179 12.10 Control of flowering by histone modifications 180 12.11 Summary 181 12.12 Problems 181 References 181 PART III: FROM RNA TO PROTEINS Chapter 13 RNA processing and transport 185 13.1 RNA processing can be thought of as steps 185 13.2 RNA capping provides a distinctive 5’ end to mRNAs 185 13.3 Transcription termination consists of mRNA 3’-end formation and polyadenylation 189 13.4 RNA splicing is another major source of genetic variation 192 13.5 Export of mRNA from the nucleus is a gateway for regulating which mRNAs actually get translated 194 13.6 Summary 196 13.7 Problems 196 References 196 Chapter 14 Fate of RNA 199 14.1 Regulation of RNA continues upon export from nucleus 199 14.2 Mechanisms for RNA turnover 199 14.3 RNA surveillance mechanisms 201 14.4 RNA sorting 202 14.5 RNA movement 203 14.6 Summary 204 14.7 Problems 204 Further reading 205 References 205 Chapter 15 Translation of RNA 207 15.1 Translation: a key aspect of gene expression 207 15.2 Initiation 209 15.3 Elongation 209 15.4 Termination 210 15.5 Tools for studying the regulation of translation 211 15.6 Specific translational control mechanisms 211 15.7 Summary 213 15.8 Problems 214 Further reading 214 References 214 Chapter 16 Protein folding and transport 215 16.1 The pathway to a protein’s function is a complicated matter 215 16.2 Protein folding and assembly 215 16.3 Protein targeting 218 16.4 Co-translational targeting 218 16.5 Post-translational targeting 219 16.6 Post-translational modifications regulating function 220 16.7 Summary 222 16.8 Problems 223 Further reading 223 References 224 Chapter 17 Protein degradation 225 17.1 Two sides of gene expression–synthesis and degradation 225 17.2 Autophagy, senescence and programmed cell death 225 17.3 Protein-tagging mechanisms 226 17.4 The ubiquitin proteasome system rivals gene transcription 228 17.5 Summary 231 17.6 Problems 231 Further reading 231 Reference 231 Index 233

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Book SynopsisComputational thinking is increasingly gaining importance in modern biology, due to the unprecedented scale at which data is nowadays produced. Bridging the cultural gap between the biological and computational sciences, this book serves as an accessible introduction to computational concepts for students in the life sciences. It focuses on teaching algorithmic and logical thinking, rather than just the use of existing bioinformatics tools or programming. Topics are presented from a biological point of view, to demonstrate how computational approaches can be used to solve problems in biology such as biological image processing, regulatory networks, and sequence analysis. The book contains a range of pedagogical features to aid understanding, including real-world examples, in-text exercises, end-of-chapter problems, colour-coded Python code, and ''code explained'' boxes. User-friendly throughout, Computational Thinking for Life Scientists promotes the thinking skills and self-efficacy rTrade Review'An excellent and very gentle introduction to bioinformatics for biologists. In contrast to books that focus on algorithms and ignore programming or focus on programming without explaining algorithms, this book is a perfect blend of both algorithms and programming!' Pavel Pevzner, Ronald R. Taylor Chair and Distinguished Professor of Computer Science, University of California at San Diego'The ability to extract quantitative information from data is an essential skill for the modern biologist. In order to maximize the benefit of programming, use of existing computational tools and effective collaboration with computational scientists, biologists must be able to 'think computationally' by gaining a more algorithmic and logical thinking. In their book, Benny Chor and Amir Rubinstein introduce fundamental computational concepts to life sciences students. Each chapter covers a distinct computational idea motivated by a concrete biological challenge. Questions embedded throughout each chapter and code examples provide hands-on practice. Similarly to the way in which chemistry is perceived as being essential to the biology curriculum, computational thinking should also be considered a part of the modern biologist's basic training. This excellent book is essential reading for undergraduate life sciences students.' Assaf Zaritsky, Ben-Gurion University of the Negev, IsraelTable of ContentsIntroduction; Part I. Programming in Python: 1. Crash introduction to python; 2. Efficiency matters – gentle intro to complexity; Part II. Sequences: 3. Sets dictionaries and hashing; 4. Regular expressions and biological patterns; Part III. Networks: 5. Basic notions in graph theory; 6. Shortest paths and breadth first search; 7. Simulation of regulatory networks; Part IV. Images: 8. Digital images representation; 9. Image processing; Part V. Limitations of Computing: 10. Mission impossible; 11. Mission infeasible; Index.

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