Integrating OMIM Mendelian Database to SPOKE for Genetics Research
Explore the integration of OMIM Mendelian database with SPOKE for genetic research, focusing on disease ontology, gene-disease relationships, and inheritance patterns. Discover how raw OMIM data is processed and utilized for mapping gene-disease associations. Dive into the analysis of disease-gene relationships and levels of evidence provided by OMIM.
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Presentation Transcript
Integrating OMIM Mendelian database to SPOKE Xiaoming (Sherman) Jia, MD MEng Baranzini Lab 4/19/2025 Genetics and SPOKE 1
Data sources Disease ontology Disease characteristics OMIM Gene-disease relationships Processed OMIM Extract relationships with highest level of evidence (phenotype mapping key = 3), inheritance patter (Mendelian or other), and modifiers Processed Disease ontology Extract OMIM ID to DOID mappings Integrate GENE-DOID mappings into SPOKE 4/19/2025 Genetics and SPOKE 2
OMIM raw data requires some text parsing Gene ENTREZ ENSEMBL Disease Cerebellar ataxia, nonprogressive, with mental retardation, 614756 (3), Autosomal dominant Parkinson disease 7, autosomal recessive early-onset, 606324 (3), Autosomal recessive {Epilepsy, generalized, with febrile seizures plus, type 5, susceptibility to}, 613060 (3), Autosomal dominant; {Epilepsy, idiopathic generalized, 10}, 613060 (3), Autosomal dominant; {Epilepsy, juvenile myoclonic, susceptibility to}, 613060 (3), Autosomal dominant CAMTA1 23261 ENSG00000171735 PARK7 11315 ENSG00000116288 GABRD 2563 ENSG00000187730 ?Charcot-Marie-Tooth disease, type 2A1, 118210 (3), Autosomal dominant; {Neuroblastoma, susceptibility to, 1}, 256700 (3), Autosomal dominant, Isolated cases; Pheochromocytoma, 171300 (3), Autosomal dominant KIF1B 23095 ENSG00000054523 CTRC 11330 ENSG00000162438 {Pancreatitis, chronic, susceptibility to}, 167800 (3), Autosomal dominant 4/19/2025 Genetics and SPOKE 3
Disease-gene relationships from OMIM: keep bolded Mapping code Inheritance Count Level of evidence Count Autosomal recessive Autosomal dominant unknown X-linked recessive X-linked dominant Multifactorial X-linked Mitochondrial Isolated cases Somatic mutation Digenic recessive Somatic mosaicism Y-linked 2828 2390 1229 208 90 69 68 49 45 23 15 4 1 Disorder is placed on the map based on its association with a gene, but the underlying defect is not known. 1 73 Disorder has been placed on the map by linkage; no mutation has been found. 2 355 The molecular basis for the disorder is known; a mutation has been found in the gene. 3 6233 a contiguous gene deletion or duplication syndrome, multiple genes are deleted or duplicated causing the phenotype 4 5 4/19/2025 Genetics and SPOKE 4
Edits to raw OMIM data Encode modifiers if disease name contains: susceptibility for (299) modifier of (27) protection against (30) resistance to (25) reduced risk of (6) Add to inheritance patterns if disease name contains : somatic or somatic mosaic (212) digenic (19) autosomal recessive (19) autosomal dominant (15) X-linked (9) Y-linked (1) 4/19/2025 Genetics and SPOKE 5
Formatted OMIM data (ready for integration) GENE OMIM DOID INHERITANCE MODIFIER DISEASE Myasthenic syndrome, congenital, 8, with pre- and postsynaptic defects AGRN 615120 110657 AR - B3GALT6 DVL1 615349 616331 50802 60765 AR AD - - Ehlers-Danlos syndrome, spondylodysplastic type, 2 Robinow syndrome, autosomal dominant 2 TMEM240 GNB1 607454 613065 50972 9952 AD - - Spinocerebellar ataxia 21 Leukemia, acute lymphoblastic, somatic SOMATIC GNB1 SKI 616973 182212 70072 2340 AD AD - - Mental retardation, autosomal dominant 42 Shprintzen-Goldberg syndrome CEP104 NPHP4 616781 606966 110994 111115 AR AR - - Joubert syndrome 25 Nephronophthisis 4 MTHFR ALPL 188050 146300 2452 110913 AD AD,AR SUSCEPTIBILITY - Thromboembolism, susceptibility to Hypophosphatasia, adult Total: 3,858 mappable gene-disease relationships 4/19/2025 Genetics and SPOKE 6
Recommended filtering after integration High-confidence Mendelian relationships (3,220): Keep Mendelian inheritance: autosomal dominant (AD), autosomal recessive (AR), X-linked dominant (XLD), X-linked recessive (XLR), X-linked (XL), Mitochondrial (MT), Digenic recessive (DR), or Y- linked (YL). May include Mendelian AND SOMATIC (hereditary cancer syndromes). Exclude relationships with modifiers (i.e. susceptibility = - ) Moderate-confidence Mendelian relationships (137): Mendelian relationships that have modifiers: susceptibility for (SUSCEPTIBILITY), modifier of (MODIFIES), protection against (PROTECTIVE), resistance to (RESISTANCE), reduced risk of (REDUCED). Low-confidence relationships (335): Relationships thatdon t have a Mendelian inheritance(i.e. inheritance = - ) Somatic (166): Inheritance = SOMATIC (i.e. not Mendelian and not unknown) 4/19/2025 Genetics and SPOKE 7
