Open data, compound repurposing, and rare diseases -- Point Loma Nazarene University
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2017-01-30
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Open data, compound repurposing, and rare diseases -- Point Loma Nazarene University
- 1. Open data, compound repurposing, and rare diseases Andrew Su, Ph.D. @andrewsu asu@scripps.edu http://sulab.org January 30, 2017 Slides: slideshare.net/andrewsu
- 2. 2 Programmer/ Comp sci Statistician/ Mathematician Biologist Data scientist Adapted from http://blog.fejes.ca/?p=2418 …teach STEM students the importance of connecting computational, mathematical, and natural sciences.
- 5. Rare disease case study #1 5 Photo: Retta Beery
- 6. 6 Bainbridge et al., STM, 2011
- 8. Rare disease case study #2 8
- 9. 9 … but no obvious treatments
- 10. 10 Bainbridge et al., STM, 2011 SPR
- 11. What differentiates SPR and NGLY1? 11 SPR
- 13. 13 NGLY1 (11 PubMed articles) Congenital disorders of glycosylation (822) PNGase (686) ERAD (1330) glycosylation (48,862) alacrima (164) Genetic interactors (3016) symptoms (109,928) 25 million articles in PubMed
- 14. The biomedical literature is massive… 14 0 200,000 400,000 600,000 800,000 1,000,000 1,200,000 1,400,000 1985 1990 1995 2000 2005 2010 2015 Number of new PubMed-indexed articles
- 15. … but it is very hard to query and compute 15
- 16. … but it is very hard to query and compute 16 Imatinib Crizotinib Erlotinib Gefitinib Sorafenib Lapatinib Dasatinib … Acute myeloid leukemia Acute lymphoblastic leukemia Chronic myelogenous leukemia Chronic lymphocytic leukemia Hodgkin lymphoma Non-Hodgkin lymphoma Myeloma … AND Gleevec Glivec STI-571 STI 571 STI571 ST1571 ST 1571 CGP-57148 CGP 57148 CGP57148 CGP57148B …
- 17. … but it is very hard to query and compute 17 EntrezGene ID HGNC symbol Description 10884 MRPS30 mitochondrial ribosomal protein S30 10914 PAPOLA poly(A) polymerase alpha 11333 PDAP1 PDGFA associated protein 1 11334 TUSC2 tumor suppressor candidate 2 130120 REG3G regenerating islet-derived 3 gamma 5068 REG3A regenerating islet-derived 3 alpha 50807 ASAP1 ArfGAP with SH3 domain, ankyrin repeat and PH domain 1 55 ACPP acid phosphatase, prostate 8853 ASAP2 ArfGAP with SH3 domain, ankyrin repeat and PH domain 2 Human genes referred to as “PAP”
- 18. 18 Biomedical research relies on effective PietroBellini https://flic.kr/p/k5jmja KNOWELDGE MANAGEMENT
- 19. Information extraction from biomedical text 19 1. Identify biomedical concepts in text … We report a case of familial systemic mastocytosis with the rare KIT K509I germ line mutation. In vitro treatment with imatinib, dasatinib and PKC412 reduced cell viability of primary mast cells harboring KIT K509I mutation. Both patients with familial systemic mastocytosis had remarkable hematological and skin improvement after three months of imatinib treatment. Leuk Res. 2014 Oct;38(10):1245-51. doi: 10.1016/j.leukres. GENES DISEASES DRUGS VARIANTS
- 20. Information extraction from biomedical text 20 imatinib dasatinib PKC412 Familial systemic mastocytosis KIT K509I 1. Identify biomedical concepts in text 2. Identify relationships between concepts Mutation of Mutation causes causes treats inhibits
- 21. 21 Goal: Assemble a network of biomedical knowledge that is comprehensive, current, computable and traceable.
- 23. The Gene Wiki project, circa 2008 23 Protein structure Symbols and identifiers Tissue expression pattern Gene Ontology annotations Links to structured databases Gene summary Protein interactions Linked references Huss, PLoS Biol, 2008
- 24. 24
- 25. Lissencephaly Gene-disease annotation databases 25 Query: Reelin (RELN)
- 26. Gene-disease annotation databases 26 Lissencephaly Familial Temporal Lobe Epilepsy Query: Reelin (RELN)
- 27. Gene-disease annotation databases 27 Lissencephaly Familial Temporal Lobe Epilepsy Otosclerosis Schizophrenia Query: Reelin (RELN)
- 28. Gene-disease annotation databases 28 Lissencephaly Familial Temporal Lobe Epilepsy Otosclerosis Schizophrenia Bipolar Disorder Autistic Disorder Alzheimer Disease Schizophrenic Psychology Breast Neoplasms … Child Development Disorders, Pervasive Cognition Cognition Disorders Dominance, Cerebral Executive Function Field Dependence- Independence Functional Laterality Choice Behavior Precursor T-Cell Lymphoblastic Leukemia-Lymphoma 27 “diseases” Psychotic Disorders Attention Attention Deficit Disorder with Hyperactivity Memory Memory, Short-Term Mental Disorders Task Performance and Analysis Tobacco Use Disorder Weight Gain Schizophrenia, Paranoid Query: Reelin (RELN)
- 29. is to data is to text biomedical Provide a database of the world’s knowledge that anyone can edit - Denny Vrandečić
- 30. Subclass of Regulates Physically interacts with Protein Neural development Property:P279 Property:P128 Property:P129 Q8054 Q1345738 VLDL receptor Q1979313 Amyloid beta A4 Q423510 Q13561329 http://www.wikidata.org/wiki/Q13561329 Decreased expression in Property:P1910 Schizophrenia Q41112 Bipolar disorder Q131755
- 32. 32
- 33. Seeding Wikidata with biomedical data • All human, mouse genes and proteins • All Gene Ontology terms • All FDA approved drugs • 9,000+ human diseases • 120 reference microbial genomes Mitraka et al (2015) Semantic Web Applications for the Life Sciences Burgstaller-Muelbacher et al (2016) Database Putman et al (2016) Database
- 34. Centralizing key data storage 34 287 language editions of Wikipedia Bioinformatics community Toxicology community Epidemiology community … …
- 35. “Show all tyrosine kinase inhibitors that are used to treat hematologic cancers.”
- 36. “Show all human membrane proteins associated with colorectal cancer.”
- 37. “Show all monoclonal antibodies used to treat melanoma.”
- 38. 39 Crowdsourcing via Citizen Science Biomedical Linked Open Data
- 40. Question: Can a group of non-scientists collectively perform concept recognition in biomedical texts? 41
- 41. 42 Experts versus crowd for concept identification 593 PubMed abstracts 6,900 mentions of “disease concepts” F = 0.87F = 0.78 $$$
- 42. 43 Experts versus crowd for concept identification 593 PubMed abstracts 6,900 mentions of “disease concepts” F = 0.87F = 0.87 $$$ • 9 days • 145 workers • Total: $630.96
- 44. 46 Paid crowdsourcing • F = 0.84 • 28 days • 212 workers • Total cost: $0 $$$ • F = 0.87 • 9 days • 145 workers • Total: $630.96 “Help science, please” Citizen Science
- 45. Does Citizen Science scale? 47 1,000,000 articles * 10 AE / article 15,828 volunteers needed 10,275 AE * 365 days 212 annotators* 28 days AE = Annotation events = Number of annotation events per year Number of annotation events per year per volunteer
- 46. Does Citizen Science scale? 48 15,828 volunteers needed 200,000 volunteers 460,000 volunteers 37,000 volunteers 1,000,000+ volunteers
- 47. Mapping the biomedical network around NGLY1 49 NGLY1
- 49. 51 A preliminary view of the NGLY1- focused biological network 1,200 contributors 3,200 documents 787,400 annotations
- 50. Finding new indications for existing drugs or therapies 53 Raynaud’s Syndrome Fish oil Abnormal platelet activity Abnormal blood viscosity High blood viscosity Elevated RBC rigidity Vasodilation Low blood triglycerides Increased prostacyclins
- 51. Finding new indications for existing drugs or therapies 54
- 52. Finding new indications for existing drugs or therapies 55 Raynaud’s Syndrome Fish oil Abnormal platelet activity Abnormal blood viscosity High blood viscosity Elevated RBC rigidity Vasodilation Low blood triglycerides Increased prostacyclins A C B B B B B B B
- 53. 56 A preliminary view of the NGLY1- focused biological network A C B B B B B B B AB B B B B B B A B B B B B B B
- 54. 57 Biomedical research relies on effective PietroBellini https://flic.kr/p/k5jmja KNOWELDGE MANAGEMENT
- 55. 58 Paul Pavlidis, UBC Lynn Schriml, U Maryland Matt and Cristina Might, Crowd volunteers and partners (Salomon) (Lotz) (Yang, Maximov) (Topol)
- 56. Louis Gioia Julee Adesara Toby Li Karthik G Erick Scott Adam Mark Kevin Xin Jake Bruggemann Mike Mayers Andra Waagmeester Max Nanis Cyrus Afrasiabi Ian MacLeod Julia Turner Ginger Tsueng Sebastien Lelong Erik Clarke Jennifer Fouquier Ben GoodChunlei Wu Shirley Willis Tobias Meissner Katie Fisch Sandip Chatterjee Ramya Gamini Greg Stupp Sebastian Burgstaller Tim Putman Nuria Queralt Rosinach Sal Loguercio M2C M2C GW GW GW GW GW GW GW
- 57. 60