Comparative Genomics: Surveys of a Finite Parts List

PPT Slide

World of Structures is even more Finite, providing a valuable simplification

A Parts List Approach to Bike Maintenance

A Parts List Approach to Bike Maintenance

Comparing Genomes in terms of Protein Structure: Surveys of a Finite Parts List

Fold Library vs. Other Fundamental Data structures

Fold Library: scop + Automatic Alignments

Some Similarities are Readily Apparent others are more Subtle

Some Similarities are Readily Apparent others are more Subtle

P-values

EVD Fits

Same EVD Results for Sequence & Struct.

Chothia & Lesk, 1986 revisited, 32 ?16K pts.

Chothia & Lesk, 1986 revisited, 32 ?16K pts.

Problems with RMS and %ID

Modern statistical language

Comparing Genomes in terms of Protein Structure: Surveys of a Finite Parts List

At What Structural Resolution Are Organisms Different?

Practical Relevance of Structural Genomics

Cross-Reference: Folds?Sequences ? Organisms

Shared Folds

Cluster Trees Grouping Initial Genomes on Basis of Shared Folds

Distribution of Folds in Various Classes

Common Folds in Genome, Varies Betw. Genomes

Characteristics of Common, Shared Folds: bab structure

Bias Problem ? Prediction, Expts.

Finding Unusual Proteins for Expt. Structural Genomics

Characterizing the Low-hanging Fruit for Experimental Structural Genomics

TM-helix “prediction”

2º Structure Prediction

Different Amino Acid Composition Should Give Different 2º Structure

Comparing Genomes in terms of Protein Structure: Surveys of a Finite Parts List

Adding Structure to Functional Genomics, Function to Structural Genomics

Functional Classification

A Simple Scheme for Functionally Classifying Protein Structures

Fold-Function Combinations

Relationship of Similarity in Sequence & Structure to that in Function

Relationship of Similarity in Sequence & Structure to that in Function II

Fold-Function Combinations #2

Fold-Function Combinations

Most Versatile Folds & Functions

Fold-Function Combinations Cross-Tabulation Summary Diagram

Compare Classifications and Genomes

Different Structure Function Relationships for Most Ancient Proteins

Comparing Genomes in terms of Protein Structure: Surveys of a Finite Parts List

Gene Expression Datasets: the Transcriptome

Composition of Genome vs. Transcriptome

Relation between Length & Expression

Composition of Transcriptome in terms of Broad Structural Classes

Which Protein Folds are Highly Expressed?

Composition of Transcriptome in terms of Functional Classes

Expression Level is Related to Localization

Bayesian System for Localizing Proteins

Bayesian System for Localizing Proteins

Results on Testing Data

Results on Testing Data #2

Extrapolation to Compartment Populations of Whole Yeast Genome: ~4000 predicted + ~2000 known

Cluster Expression Data, Relate to MIPS Functional Category

Correlation of Functional Class and Expression – not that strong

Whole Genome Phenotype Profiles

Phenotype ORF Clustering

GeneCensus

Comparing Genomes in terms of Protein Structure: Surveys of a Finite Parts List

Macromolecular Motions

Motions DB: Information, Size, then Packing Based Classification

Interface Packing and Motions

Packing Based Classification: Hinge v Shear

Proteins With Shear Motions are Often Divided into Layers

Packing Based Classification: Hinge v Shear

Voronoi Volumes, the Natural Way to Measure Packing

ProtOr Parameter Set: Standard Radii & Volumes

Motion Analysis Server, Morph Movies

5 Movies Generated by the Server

Comparing Genomes in terms of Protein Structure: Surveys of a Finite Parts List