Lyle Ungar, University of Pennsylvania Introduction to BioInformatics GCB/CIS535.
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Transcript of Lyle Ungar, University of Pennsylvania Introduction to BioInformatics GCB/CIS535.
Lyle Ungar, University of Pennsylvania
Introduction to Introduction to BioInformaticsBioInformatics
GCB/CIS535GCB/CIS535
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Course OverviewCourse OverviewCourse OverviewCourse Overview
Sequence alignment Dynamic programming Blast and its variants
statistical significance Motif and promoter prediction
Gene prediction Homology and HMMs
Gene expression Experiment design Interpretation: clustering
Proteomics Use of mass spectrometry
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Sequence AlignmentSequence AlignmentSequence AlignmentSequence Alignment
Choices nucleotide vs. amino acid global vs. local repeat masking
Motif finding Position weight matrices
PAM, BLOSUM CONSENSUS EM and Gibbs sampling methods
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Promoter FindingPromoter FindingPromoter FindingPromoter Finding
CpG islands Transcription Factor Binding sites
TATA, GC, and CAAT boxes Transfac and Jasper libraries
FirstExon
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Gene FindingGene FindingGene FindingGene Finding
Homology Conservation between species
Hidden Markov Models (HMMs) Acceptors & donors Coding & non-coding Frame shifts
Regression Linear regression Artificial neural networks
Future Conditional Random Fields (CRFs)
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Gene ExpressionGene ExpressionGene ExpressionGene Expression
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Gene ExpressionGene ExpressionGene ExpressionGene Expression Uses
Finding Differentially Expressed Genes Gene List Annotation
Technology Spotted array (two color) and Affimetrics (one color) Experiment Execution (Process Control)
Experimental design Replicates Matched experiments
Controls / reference samples
Analysis Probes to Genes Normalization Sample Quality Control Statistical Significance of Over Representation
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ClusteringClusteringClusteringClustering
Clustering methods Hierarchical K-means
Key decisions Standardize data? How many clusters?
Dimension reduction PCA - Principal Components Analysis SOM - Self Organizing Maps
Assessment Cluster purity
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Methods for protein
identification
ProteomicsProteomicsProteomicsProteomics
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ProteomicsProteomicsProteomicsProteomics
Uses Toxicology Compare diseased vs. normal cells Alternative splicing Post-translational modifications Together with genomics
Mass spectrometry Mass fingerprinting Sequence tags Cross correlation with simulated mass spectra E.g. Sequest and mascot Problem with introns Y-ions and b-ions Tandem mass spec
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Future DirectionsFuture DirectionsFuture DirectionsFuture Directions
Regulatory mechanisms Transcription (“gene expression”) Translation (“protein production”) Acetylation (of lycine) Phosphorylation, Other protein, RNA and DNA modification
Binding between DNA, RNA, Protein
Comparison across species Systems biology
Metabolic modeling
Combining data
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Gene Regulatory NetworkGene Regulatory NetworkGene Regulatory NetworkGene Regulatory Network
Sea urchin development