1. Mining Brain-Related Transcription Factor- Disease Relationships for Novel Linkages Unified Medical Language System (UMLS) Specialised Databases Atlas Data Warehouse Warren Cheung 1,3,4, BF Francis Ouellette 2,3, Wyeth W Wasserman 2,4 1 Bioinformatics Program, University of British Columbia, Vancouver, BC, Canada. E-mail: wac@dnahelix.org 2 Department of Medical Genetics, University of British Columbia. 3 University of British Columbia Bioinformatics Centre. 4 Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute. UniProt Gene Ontology Annotation TF Cat PAZAR (Online) Mendelian Inheritance in Man Medical Subject Headings (MeSH) ICD 9/10 SnoMed CT HPRD RefSeq BIND GenBank Results Entrez Gene Total Genes 2 631 524 Human Genes 38 624 Human Transcription Factor (TF) Genes 1 192 Gene Reference Into Function (GeneRIFs) Genes with GeneRIFs 33 216 Human TF Genes with GeneRIFs 914 Medical Subject Headings MeSH terms 47 143 Unique MeSH terms 24 355 MeSH terms under “Brain Diseases” 312 PubMed / MEDLINE PubMed Articles 16 120 074 PubMed Articles with MeSH annotation 15 806 221 Brain Disease (MeSH) PubMed Articles 660 538 PubMed Articles referenced by Human TF GeneRIFs 15 741 PubMed Articles marked with MeSH Brain Disease terms, linked by Human TF GeneRIFs 351 Selected TF Gene Associations to Brain Diseases GeneBrain DiseasePapers TP53Brain Diseases 43 Brain Neoplasms 27 Ataxia Telangiectasia 6 TNFBrain Diseases 27 Alzheimer Disease 5 ESR1Brain Diseases 13 Alzheimer Disease 7 PPARGBrain Diseases 12 Brain Neoplasms 4 POU1F1Brain Diseases 11 Pituitary Neoplasms 4 Hypopituitarism 4 NR4A2Brain Diseases 9 Parkinson Disease 9 CTNNB1Brain Disease 7 Alzheimer Disease 7 TBPBrain Diseases 9 Spinocerebellar Ataxias 6 ARXSpasms, Infantile 6 HIF1ABrain Neoplasms 5 … 780 Total Gene-Brain Disease pairs OMIM verified PubMed verified Brain Diseases by Number of Genes Brain Disease (MeSH Term)Human TF Genes Brain Diseases 146 Dementia 68 Brain Neoplasms 54 Alzheimer Disease 39 Basal Ganglia Diseases 31 … 93 MeSH terms have a human TF gene reference NLM UMLS Metathesaurus database of medical terminologies Discovering Links Between Genes and Disease TF-Cat 4 Annotated transcription factor database Validation Freeze database contents at a cut-off date and compare against more recent discoveries. Withhold and verify using the Mendelian Inheritance in Man (MIM) Database NLM Medical Subject Heading controlled vocabulary thesaurus Atlas Data Warehouse 3 unified access to nucleotide, protein, interactions and ontology annotations Open Access Integrated, Unified Repository Efficient Programmatic Framework Exploration of Gene-Disease Relationships Goals PAZAR 4 database of gene regulatory elements Entrez Gene NCBI Entrez Gene Gene Reference into Function annotations Gene Ontology annotations PubMed Design Statistics Statistical Evaluation of Support Secondary and Tertiary Relationships Future Work Human TF Genes with GeneRIFs to Brain Disease PubMed Articles 146 MeSH Annotations Gene Ontology (GO) Terms