BIOINFORMATICS GUIDE
FOOLISH ASSUMPTIONS HOW THIS BOOK IS ORGANIZED PART I: GETTING STARTED IN BIOINFORMATICS PART II: A SURVIVAL GUIDE TO BIOINFORMATICS PART III: BECOMING A PRO IN SEQUENCE ANALYSIS PART IV: BECOMING A SPECIALIST: ADVANCED BIOINFORMATICS TECHNIQUES PART V: THE PART OF TENS ICONS USED IN THIS BOOK WHERE TO GO FROM HERE WHAT IS BIOINFORMATICS? ANALYZING PROTEIN SEQUENCES A BRIEF HISTORY OF SEQUENCE ANALYSIS READING PROTEIN SEQUENCES FROM N TO C WORKING WITH PROTEIN 3-D STRUCTURES PROTEIN BIOINFORMATICS COVERED IN THIS BOOK ANALYZING DNA SEQUENCES READING DNA SEQUENCES THE RIGHT WAY THE TWO SIDES OF A DNA SEQUENCE PALINDROMES IN DNA SEQUENCES ANALYZING RNA SEQUENCES RNA STRUCTURES: PLAYING WITH STICKY STRANDS MORE ON NUCLEIC ACID NOMENCLATURE DNA CODING REGIONS: PRETENDING TO WORK WITH PROTEIN SEQUENCES TURNING DNA INTO PROTEINS: THE GENETIC CODE MORE WITH CODING DNA SEQUENCES DNA/RNA BIOINFORMATICS COVERED IN THIS BOOK WORKING WITH ENTIRE GENOMES GENOMICS: GETTING ALL THE GENES AT ONCE GENOME BIOINFORMATICS COVERED IN THIS BOOK INTRODUCTION BECOMING AN INSTANT EXPERT WITH PUBMED/MEDLINE FINDING OUT ABOUT A PROTEIN BY ITS NAME SEARCHING PUBMED USING AUTHOR’S NAMES SEARCHING PUBMED USING FIELDS SEARCHING PUBMED USING LIMITS A FEW MORE TIPS ABOUT PUBMED RETRIEVING PROTEIN SEQUENCES EXPASY: A PRIME INTERNET SITE FOR PROTEIN INFORMATION MORE ADVANCED WAYS TO RETRIEVE PROTEIN SEQUENCES RETRIEVING A LIST OF RELATED PROTEIN SEQUENCES RETRIEVING DNA SEQUENCES NOT ALL DNA IS CODING FOR PROTEIN GOING FROM PROTEIN SEQUENCES TO DNA SEQUENCES RETRIEVING THE DNA SEQUENCE RELEVANT TO MY PROTEIN USING BLAST TO COMPARE MY PROTEIN SEQUENCE TO OTHER PROTEIN SEQUENCES MAKING A MULTIPLE PROTEIN SEQUENCE ALIGNMENT WITH CLUSTALW READING INTO GENES AND GENOMES PROKARYOTES: SMALL BUGS, SIMPLE GENES EUKARYOTES: BIGGER BUGS, COMPLEX GENES MAKING USE (AND SENSE) OF GENBANK MAKING SENSE OF THE GENBANK ENTRY OF A PROKARYOTIC GENE MAKING SENSE OF THE GENBANK ENTRY OF AN EUKARYOTIC MRNA MAKING SENSE OF A GENBANK EUKARYOTIC GENOMIC ENTRY WORKING WITH RELATED GENBANK ENTRIES RETRIEVING GENBANK ENTRIES WITHOUT ACCESSION NUMBERS USING A GENE-CENTRIC DATABASE WORKING WITH WHOLE-GENOME DATABASES WORKING WITH COMPLETE VIRAL GENOMES WORKING WITH COMPLETE BACTERIAL GENOMES MORE BACTERIAL GENOMICS AT TIGR MICROBES FROM THE ENVIRONMENT AT DOE EXPLORING THE HUMAN GENOME FINDING OUT ABOUT THE ENSEMBL PROJECT FROM TRANSLATED ORFS TO MATURE PROTEINS ORFS: WHAT YOU SEE IS NOT WHAT YOU GET A PERSONAL FINAL DESTINATION FOR EACH PROTEIN A COMBINATORIAL DIVERSITY OF FOLDS AND FUNCTIONS READING A SWISS-PROT ENTRY DECIPHERING THE EGFR SWISS-PROT ENTRY GENERAL INFORMATION ABOUT THE ENTRY NAME AND ORIGIN OF THE PROTEIN THE REFERENCES THE COMMENTS THE CROSS-REFERENCES THE KEYWORDS THE FEATURES FINALLY, THE SEQUENCE ITSELF FINDING OUT MORE ABOUT YOUR PROTEIN FINDING OUT MORE ABOUT “MODIFIED AMINO ACIDS SOME ADVANCED BIOCHEMISTRY SITES FINDING OUT MORE ABOUT BIOCHEMICAL PATHWAYS FINDING OUT MORE ABOUT PROTEIN STRUCTURES FINDING OUT MORE ABOUT MAJOR PROTEIN FAMILIES CATCHING ERRORS BEFORE IT’S TOO LATE REMOVING VECTOR SEQUENCES CASES WHEN YOU SHOULDN’T DISCARD YOUR SEQUENCE COMPUTING/VERIFYING A RESTRICTION MAP DESIGNING PCR PRIMERS ANALYZING DNA COMPOSITION ESTABLISHING THE G+C CONTENT OF YOUR SEQUENCE COUNTING WORDS IN DNA SEQUENCES COUNTING LONG WORDS IN DNA SEQUENCES EXPERIMENTING WITH OTHER DNA COMPOSITION ANALYSES FINDING INTERNAL REPEATS IN YOUR SEQUENCE IDENTIFYING GENOME-SPECIFIC REPEATS IN YOUR SEQUENCE FINDING PROTEIN-CODING REGIONS ORFING YOUR DNA SEQUENCE ANALYZING YOUR DNA SEQUENCE WITH GENEMARK FINDING INTERNAL EXONS IN VERTEBRATE GENOMIC SEQUENCES COMPLETE GENE PARSING FOR EUKARYOTIC GENOMES ANALYZING YOUR SEQUENCE WITH GENOMESCAN ASSEMBLING SEQUENCE FRAGMENTS MANAGING LARGE SEQUENCING PROJECTS WITH PUBLIC SOFTWARE ASSEMBLING YOUR SEQUENCES WITH CAP3 BEYOND THIS CHAPTER DOING BIOCHEMISTRY ON A COMPUTER PREDICTING THE MAIN PHYSICO-CHEMICAL PROPERTIES OF A PROTEIN INTERPRETING PROTPARAM RESULTS DIGESTING A PROTEIN IN A COMPUTER DOING PRIMARY STRUCTURE ANALYSIS LOOKING FOR TRANSMEMBRANE SEGMENTS LOOKING FOR COILED-COIL REGIONS PREDICTING POST-TRANSLATIONAL MODIFICATIONS IN YOUR PROTEIN LOOKING FOR PROSITE PATTERNS INTERPRETING SCANPROSITE RESULTS FINDING KNOWN DOMAINS IN YOUR PROTEIN CHOOSING THE RIGHT COLLECTION OF DOMAINS FINDING DOMAINS WITH INTERPROSCAN INTERPRETING INTERPROSCAN RESULTS FINDING DOMAINS WITH THE CD SERVER INTERPRETING AND UNDERSTANDING CD SERVER RESULTS FINDING DOMAINS WITH MOTIF SCAN DISCOVERING NEW DOMAINS IN YOUR PROTEINS MORE PROTEIN ANALYSIS FOR FREE OVER THE INTERNET UNDERSTANDING THE IMPORTANCE OF SIMILARITY THE MOST POPULAR DATA-MINING TOOL EVER: BLAST BLASTING PROTEIN SEQUENCES UNDERSTANDING YOUR BLAST OUTPUT BLASTING DNA SEQUENCES THE BLAST WAY OF DOING THINGS CONTROLLING BLAST: CHOOSING THE RIGHT PARAMETERS CONTROLLING THE SEQUENCE MASKING CHANGING THE BLAST ALIGNMENT PARAMETERS CONTROLLING THE BLAST OUTPUT MAKING BLAST ITERATIVE WITH PSI-BLAST PSI-BLASTING PROTEIN SEQUENCES AVOIDING MISTAKES WHEN RUNNING PSI-BLAST DISCOVERING AND USING PROTEIN DOMAINS WITH BLAST AND PSI-BLAST SIMILARITY SEARCHES FOR FREE OVER THE INTERNET MAKING SURE YOU HAVE THE RIGHT SEQUENCES AND THE RIGHT METHODS CHOOSING THE RIGHT SEQUENCES CHOOSING THE RIGHT METHOD MAKING A DOT PLOT CHOOSING THE RIGHT DOT-PLOT FLAVOR USING DOTLET OVER THE INTERNET DOING BIOLOGICAL ANALYSIS WITH A DOT PLOT MAKING LOCAL ALIGNMENTS OVER THE INTERNET CHOOSING THE RIGHT LOCAL-ALIGNMENT FLAVOR USING LALIGN TO FIND THE TEN BEST LOCAL ALIGNMENTS INTERPRETING THE LALIGN OUTPUT MAKING GLOBAL ALIGNMENTS OVER THE INTERNET USING LALIGN TO MAKE A GLOBAL ALIGNMENT ALIGNING PROTEINS AND DNA FREE PAIRWISE SEQUENCE COMPARISONS OVER THE INTERNET FINDING OUT IF A MULTIPLE SEQUENCE ALIGNMENT CAN HELP YOU IDENTIFYING SITUATIONS WHERE MULTIPLE ALIGNMENTS DO NOT HELP HELPING YOUR RESEARCH WITH MULTIPLE SEQUENCE ALIGNMENTS CHOOSING THE RIGHT SEQUENCES THE KINDS OF SEQUENCES YOU’RE LOOKING FOR GATHERING YOUR SEQUENCES WITH ONLINE BLAST SERVERS CHOOSING THE RIGHT METHOD OF MULTIPLE SEQUENCE ALIGNMENT USING CLUSTALW ALIGNING SEQUENCES AND STRUCTURES WITH TCOFFEE CRUNCHING LARGE DATASETS WITH MUSCLE INTERPRETING YOUR MULTIPLE SEQUENCE ALIGNMENT RECOGNIZING THE GOOD PARTS IN A PROTEIN ALIGNMENT TAKING YOUR MULTIPLE ALIGNMENT FURTHER COMPARING SEQUENCES THAT YOU CAN’T ALIGN MAKING MULTIPLE LOCAL ALIGNMENTS WITH THE GIBBS SAMPLER SEARCHING CONSERVED PATTERNS INTERNET RESOURCES FOR DOING MULTIPLE SEQUENCE COMPARISONS MAKING MULTIPLE ALIGNMENTS WITH CLUSTALW AROUND THE CLOCK FINDING YOUR FAVORITE ALIGNMENT METHOD SEARCHING FOR MOTIFS OR PATTERNS GETTING YOUR MULTIPLE ALIGNMENT IN THE RIGHT FORMAT RECOGNIZING THE MAIN FORMATS WORKING WITH THE RIGHT FORMAT CONVERTING FORMATS WATCHING OUT FOR LOST DATA USING JALVIEW TO EDIT YOUR MULTIPLE ALIGNMENT ONLINE STARTING JALVIEW EDITING A GROUP OF SEQUENCES USEFUL FEATURES OF JALVIEW SAVING YOUR ALIGNMENT IN JALVIEW PREPARING YOUR MULTIPLE ALIGNMENT FOR PUBLICATION USING BOXSHADE LOGOS EDITING AND ANALYZING MULTIPLE SEQUENCE ALIGNMENTS FOR FREE OVER THE INTERNET FINDING MULTIPLE-SEQUENCE-ALIGNMENT EDITORS FINDING TOOLS TO INTERPRET YOUR MULTIPLE SEQUENCE ALIGNMENT FINDING TOOLS FOR BEAUTIFYING YOUR MULTIPLE ALIGNMENTS FROM PRIMARY TO SECONDARY STRUCTURES PREDICTING THE SECONDARY STRUCTURE OF A PROTEIN SEQUENCE PREDICTING ADDITIONAL STRUCTURAL FEATURES FROM THE PRIMARY STRUCTURE TO THE 3-D STRUCTURE RETRIEVING AND DISPLAYING A 3-D STRUCTURE FROM A PDB SITE GUESSING THE 3-D STRUCTURE OF YOUR PROTEIN LOOKING AT SEQUENCE FEATURES IN 3-D FINDING PROTEINS WITH SIMILAR SHAPES FINDING OTHER PDB VIEWERS CLASSIFYING YOUR PDB STRUCTURE DOING HOMOLOGY MODELING FOLDING PROTEINS IN A COMPUTER THREADING SEQUENCES ONTO PDB STRUCTURES LOOKING AT STRUCTURES IN MOVEMENT PREDICTING INTERACTIONS PREDICTING, MODELING AND DRAWING RNA SECONDARY STRUCTURES USING MFOLD INTERPRETING MFOLD RESULTS FORCING INTERACTION IN MFOLD SEARCHING DATABASES AND GENOMES FOR RNA SEQUENCES FINDING TRNAS IN A GENOME USING PATSCAN TO LOOK FOR RNA PATTERNS FINDING THE “NEW” RNAS: MIRNAS AND SIRNAS DOING RNA ANALYSIS FOR FREE OVER THE INTERNET STUDYING EVOLUTION WITH RIBOSOMAL RNA FINDING THE SMALL, NON-CODING RNA YOU NEED GENERIC RNA RESOURCES FINDING OUT WHAT PHYLOGENETIC TREES CAN DO FOR YOU PREPARING YOUR PHYLOGENETIC DATA CHOOSING THE RIGHT SEQUENCES FOR THE RIGHT TREE PREPARING YOUR MULTIPLE SEQUENCE ALIGNMENT BUILDING THE KIND OF TREE YOU NEED COMPUTING YOUR TREE KNOWING WHAT’S WHAT IN YOUR TREE DISPLAYING YOUR PHYLOGENETIC TREE DOING PHYLOGENY FOR FREE OVER THE INTERNET FINDING ONLINE RESOURCES FINDING GENERIC RESOURCES COLLECTIONS OF ORTHOLOGOUS GENES KEEP IN MIND: YOUR DATA IS NEVER SECURE ON THE WEB REMEMBER THE SERVER, THE DATABASE, AND THE PROGRAM VERSION YOU USED WRITE DOWN THE SEQUENCE-IDENTIFICATION NUMBERS WRITE DOWN THE PROGRAM PARAMETERS SAVE YOUR INTERNET RESULTS THE RIGHT WAY USE E-VALUES MAKE SURE YOU CAN TRUST YOUR ALIGNMENTS USE DIFFERENT PROGRAMS TO CHECK BORDERLINE RESULTS STAY AWAY FROM UNPUBLISHED METHODS! DATABASES ARE NOT LIKE GOOD WINE JUST BECAUSE IT LOOKS FREE DOESN’T MEAN IT IS FREE BITING THE BULLET AT THE RIGHT TIME TEN MAJOR DATABASES TEN MAJOR BIOINFORMATICS SOFTWARE PROGRAMS TEN MAJOR RESOURCE LOCATORS SOME PLACES TO FIND OUT WHAT’S REALLY GOING ON