1	PIR Integrated Resources and Data-Mining Tools for Functional Genomics and Proteomics Zhang-Zhi Hu, M.D. Bioinformatics Scientist, Protein Information Resource Georgetown University Medical Center, Washington, DC
2	Functional Genomics and Proteomics Study of Biological Systems Based on Global Knowledge of Genomes, Transcriptomes, Proteomes, Metabolomes Genome: All the Genetic Material in the Chromosomes Transcriptome: Entire Set of Gene Transcripts Proteome: Entire Set of Proteins Metabolome: Entire Set of Metabolites
3	Protein Information Resource (PIR) Goal: An Integrated Public Resource of Protein Informatics to Support Genomic/Proteomic Research & Scientific Discovery Components Database: Data Organization & Information Retrieval Software: Data Analysis & Sequence Annotation Challenges Voluminous, Complex, Dynamic Data from Heterogeneous Sources Integrated, Classification Approach Databases: PIR-PSD, PIR-NREF, iProClass Integrated Analysis System: Knowledge Base System Database Interoperability: Ontology, XML, Relational Schema, iProClass Framework
4	PIR Web Site (http://pir.georgetown.edu)
5	Protein Family Classification Superfamily, Domain, and Motif Classification Superfamily Concept End-to-End Similarity & Same Overall Domain Architecture Significance Improve Sensitivity of Protein Identification Provide Complete Clustering for Database Organization Detect and Correct Genome Annotation Errors Systematically Drive Other Annotations Stimulate Evolution, Genomics and Proteomics Research
6	Genome Sequence Annotation
7	Genome Era Challenges: Transitive Catastrophe Error Propagation: At least 17 Sequences Incorrectly Named as IMP Dehydrogenase or Related (Propagated to KEGG & WIT)
8	PIR-NREF Database Non-Redundant REFerence Protein Sequence Database Comprehensiveness: PIR-PSD, Swiss-Prot, TrEMBL, RefSeq, GenPept, PDB Timeliness: Biweekly Updates (~ 1,000,000 Sequences) Non-Redundancy: by Sequence Identity & Taxonomy (Species) Source Attribution: Protein IDs and Names from Underlying Databases, Sequence, Taxonomy, Bibliography Related Sequences: Identical Sequences from Different Species, Complete Substring, >=95% Sequence Identity Applications Protein Identification: Full-Scale or Species-Based Sequence Analysis and Text Search Detection of Annotation Errors Development of Protein Name Ontology FTP Distribution: XML and FASTA Formats
9	PIR-NREF Report (I)
10	PIR-NREF Report (II) Annotation Discrepancy of Multi-Domain Proteins
11	PIR-NREF Database (http://pir.georgetown.edu/pirwww/search/pirnref.shtml)
12	PIR Searches (I)
13	PIR Searches (II)
14	Data Integration Challenges Voluminous, Complex & Dynamic Data from Heterogeneous Sources in Distributed Networking Environment Data Warehouse Local Copy of Databases in a Unified Database Schema Allows Local Control of Data; Update Problem Hypertext Navigation Browsing Model with Hypertext Links Allows Direct Interaction; Easily Lost in Cyberspace iProClass Approach Data Warehouse + Hypertext Navigation Rich Links (Links + Executive Summaries) between Database Objects An Integrated Platform for Describing Comprehensive Family Relationships and Structural and Functional Features of Proteins
15	iProClass Database An Integrated Platform for Describing Comprehensive Family Relationships and Structural and Functional Features of Proteins Classification Scheme: Superfamily/Family & Domain/Motif Superfamily/Family (Global): Full-Length Similarity with Same Domain Arrangement Domain/Motif (Local): Structural/Functional Units & Sites Sequence and Family Data Non-Redundant, Annotated PIR-PSD, Swiss-Prot, TrEMBL Sequences: ~827,000 Superfamilies (~36,000), Families (>145,000), Domains (>3700), Motifs (>1300), Post-Translational Modifications (>280) Superfamily and Protein Summary Reports Modular Framework: Extensibility, Flexibility, Customization
16	iProClass Overview
17	iProClass - Sequence Report (I)
18	Bibliography Information Display From Curated Databases (e.g., PIR-NREF, SGD) From User Submission From Computer-Mapping (e.g. Gene Symbol)
19	Functional Classification Gene Ontology (GO) Three Ontologies: Biological Process, Molecular Function, Cellular Component Consortium: FlyBase, SGD, MGI, TAIR, WormBase, Pombase
20	KEGG Metabolic & Regulatory Pathways pathway
21	DIP Protein-Protein Interactions
22	iProClass - Sequence Report (II)
23	Protein Structural Classification CATH Classification
24	PIR-RESID Post-Translational Modification Database
25	iProClass - Superfamily Report
26	Integrated Protein Knowledge Base System
27	Integrated Knowledge Base
28	Protein Informatics for Expression Analysis
29	Knowledge Base for Functional Genomics & Proteomics Homology Based Sequence & Structural Families Functionally Linked Genetic Association: Gene Clustering on Chromosomes, Multi-Domain Proteins Function Association: Pathways, Biological Processes, Networks, Protein-Protein Interactions, Protein Complexes Correlated Evolution: Related Phylogenetic Profile Correlated Expression: mRNA/Protein Expression
30	Acknowledgments Sponsors NIH: NLM (PIR) NSF: BDI (iProClass); ITR (Ontology) PIR Team Cathy Wu, Winona Barker, Robert Ledley, Hongzhan Huang, Lai-Su Yeh, Bruce Orcutt, CR Vinayaka, Zhang-Zhi Hu, Baris Suzek, Yongxing Chen, Jim Zhang, Peter Kourtesis, Jorge L. Cardenas, Leslie Arminski