BCB 444544 Introduction to Bioinformatics

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BCB 444/544 - Introduction to Bioinformatics
Lecture 12 What Have We Learned from
Unicellular Genomes? 12_Sept18
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Assignments Reading Exercises
Homework 2

• Mon Sept 18 Wed Sept 21
• CH Chp 2.3 pp 83 - 109
• Also, DQs MMs
• Homework 2 - Due Mon, Sept 18 - TODAY

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Announcements Exam I

• Exam 1 - Friday, Sept. 22, In class
• Study Aids
• Study Guide 1 - Available online today (Mon)
• PPTs - Available online
• Labs 1,2,3 - All graded returned by Class on
  Wed
• Lab 4 - Answer Key posted by Class on Wed
• Homework 2 - Answer Key posted today
• - Graded returned by Lab on Thursday
• Review Session - During Lab session on Thursday
• Office Hours? - By appt this week

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Announcements Upcoming Seminars in
Bioinformatics/Genomics

• Mon Sept 18
• David Nelson (Harvard) DNA unzipping and motor
  proteins effect of the genetic code
• Physics Seminar - 410 PM in 5 Physics
• Paul Coussens (U Michigan) The use of functional
  genomics to decipher a complex disease Bovine
  paratuberculosis
• Immunobiology Fall Workshop - 410 PM in 1414
  MBB
• For additional upcoming seminar listings, see
• http//www.bcb.iastate.edu/seminars/index.html

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Gene Prediction Protein Function Prediction
What is a gene? Segment of DNA, some of which is
"structural," i.e., transcribed to give a
functional RNA product, some of which is
"regulatory" Gene prediction - the task of
predicting structural boundaries features of
putative genes in genomic sequences

• What do we mean by "protein function"? Tough to
  answer because there are many "types" "levels"
  of protein function
• Function prediction - the task of annotating a
  gene or assigning a "function" to a gene product
  (usually, a protein)

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In Lab last weekGene Prediction

• ORF-Finder (NCBI) - find all the putative
  ORFs in a given sequence
• GeneMark (Ga Tech) - a Gene Prediction Server
  with a nice interface, good documentation
• GenSeqer (ISU) - our very own Volker Brendel's
  excellent server!

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Gene Prediction Protein Function Prediction
What is a gene? Segment of DNA, some of which is
"structural," i.e., transcribed to give a
functional RNA product, some of which is
"regulatory." Gene prediction - the task of
predicting structural boundaries features of
genes in genomic sequences

• What do we mean by "protein function"? Tough to
  answer because there are many "levels" of protein
  function. Must consider protein function from
  several different perspectives
• Function prediction - the task of annotating a
  gene or assigning a "function" to a gene product
  (usually, a protein)

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In Lab last weekProtein Function Prediction

• Sequence-based (Structure-based later)
• Protein sequence homology (e.g., BLAST,
  PSI-BLAST)
• MOTIF detection (e.g., PROSITE)
• Patterns vs Profiles
• Hidden Markov Models (HMMs) (e.g., SuperFam)
• Metaservers (e.g., JAFA http//jafa.burnham.org/
  )

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Hierarchical Levels of Protein Function

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Gene Ontology (GO)

• Gene Ontology (GO) project/consortium
• Purpose provide controlled vocabulary to
  describe gene and gene product attributes in any
  organism
• GO comprises 3 ontologies that describe gene
  products in terms of their associated
• 1 - Biological processes
• 2 - Cellular components
• 3 - Molecular functions

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Chp 2 - Genome Sequence Acquisition Analysis
Chp 2 - Campbell Heyer Companion Website

• 2.1 How are Genomes Sequenced?
• What Is Genomics?
• How Are Whole Genomes Sequenced?
• How Are Organisms Picked for Genome Sequencing?
• Math Minute 2.1 What Can You Learn from a Dot
  Plot?
• Math Minute 2.2 How Do You Find Motifs?
• Can We Predict Protein Functions from DNA
  Sequence?
• Math Minute 2.3 What Are "Positives"
• What Do They Have to Do with E-values?

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Chp 2 - Genome Sequence Acquisition Analysis

• 2.1 How are Genomes Sequenced? - cont.
• What Shapes Are the Proteins?
• Does Structure Reveal Function?
• Why Do the Databases Contain So Many Partial
  Sequences?
• Which Sequencing Method Worked Better?
• Annotated Genomes Online
• How Many Proteins Can One Gene Make?
• Can the Genome Alter Gene Expression Without
  Changing the DNA Sequence?
• What Is the Fifth Base in DNA? Methyl-Cytosine
• Imprinting, Methylation, and Cancer
• SUMMARY 2.1

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Chp 2 - Genome Sequence Acquisition Analysis
2.2 What Have We Learned from Unicellular
Genomes? ? Why Do I Get So Many Pimples? ?
Which Genes Cause Pimples? ? Are All Bacteria
Living in Us Bad for Us? ? Can Microbial Genomes
Become Dependent upon Human Genes? ? What Is the
Minimum Number of Genes Possible? ? Are All
Viral Genomes Smaller than All Bacterial Genomes?
? Is Mimivirus Alive? ? Do Genomes Reflect an
Organism's Ecological Niche? Math Minute 2.4
Can You Estimate the Number of Inversions in a
Dot Plot?
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Chp 2 - Genome Sequence Acquisition Analysis
2.2 What Have We Learned from Unicellular
Genomes? - cont. ? Why Is MED4's Genome So
Small? ? How Many Genome Changes Are Required
Before a New Species Is Created? ? What Kind of
Organism Causes Malaria? ? What Sort of Genome
Does Plasmodium Possess? ? Is the Predicted
Proteome Equally Bizarre? ? Is There a Model
Eukaryote Genome? ? What Did the Investigators
Predict for the Future of Genomics? ? Epilog for
the Yeast Genome SUMMARY 2.2
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Chp 2 - Genome Sequence Acquisition Analysis

• 2.3 What Have We Learned from Metazoan Genomes?
  
• ? Are Animal Genomes Harder to Finish?
• ? What Are Polytene Chromosomes?
• ? What Makes a Fly Different from Other
  Eukaryotes?
• ? Is the Fly Still a Good Model Organism?
• ? Fly Genome Epilog
• ? Do We Need Two Plant Genome Sequences?
• ? Plants Seem Simpler than Animals, but Are Their
  Genomes?
• ? Can We Draw Any Conclusions from Draft
  Sequences?
• ? What Lessons Have We Learned?
• ? Rice Epilog
• ? What Can We Possibly Learn from a Puffer Fish
  Genome?
• ? Did the Genome Reveal Any Surprises?
• Are There More Big Lessons from Tetraodon?
• ? What Makes Humans Different?

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Chp 2 - Genome Sequence Acquisition Analysis
2.3 What Have We Learned from Metazoan Genomes?
- cont. Math Minute 2.5 How Do You Fit a Line
to Data? ? Whose DNA Did We Sequence? ? Can We
Describe a Typical Human Gene? ? Human Genome
Epilog ? What Is the Next Goal in Human
Genomics? SUMMARY 2.3 Chapter 2 Conclusions
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Fig 2.1
DNA replication -
Terrible figure!!
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Box 2.1 Table - Genomes Completed (out
of date!)
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Fig 2.3
Sequences chromats in assembly archive
Chromats? Chromatograms
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Fig 2.3
Sequences chromats in assembly archive
DETAIL
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Fig 2.4
Comparing draft finished versions of
human genome sequence (chromosome 7)
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Table MM2.1
What is a TATA box? Note high degree of
conservation
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Tables MM2.2 and MM2.3
PWM Position Weight Matrix or PSWM Position
Specific Weight Matrix or PSSM Position
Specific Scoring Matrix
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Table MM2.4
The famous BLOSUM62
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Table MM2.5
BLOSUM62 in action
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Fig 2.6
2 Different proteins produced by alternative
RNA splicing
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Fig 2.9
Ugh - I don't think I can lecture on this!
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Fig 2.16
Mimivirus genome map - Why "special"?
What is a COG?