Crowdsourcing Biology: The Gene Wiki, BioGPS, and Citizen Science

  • Published on
    23-Aug-2014

  • View
    1.307

  • Download
    0

Embed Size (px)

DESCRIPTION

Screencast video now at: https://www.youtube.com/watch?v=oe7pjHJU-z4 Talk info at http://1.usa.gov/1kPcRxC

Transcript

  • Crowdsourcing Biology: The Gene Wiki, BioGPS and GeneGames.org Andrew Su, Ph.D. @andrewsu asu@scripps.edu http://sulab.org May 14, 2014 CBIIT Slides: slideshare.net/andrewsu Citizen Science!
  • Few genes are well annotated 2 Data: NCBI, February 2013 41% 65% CTNNB1 VEGFA SIRT1 FGFR2 TGFB1 TP53 MEF2C BMP4 LEF1 WNT5A TNF 20,473 protein- coding genes Genes, sorted by decreasing counts GOAnnotation Counts
  • because the literature is sparsely curated? 3 0 200,000 400,000 600,000 800,000 1,000,000 1,200,000 1983 1988 1993 1998 2003 2008 2013 Number of new PubMed-indexed articles
  • because the literature is sparsely curated? 4 0 10 20 30 40 1983 1988 1993 1998 2003 2008 2013 Average capacity of human scientist
  • 5 311,696 articles (1.5% of PubMed) have been cited by GO annotations
  • 6 0 Sooner or later, the research community will need to be involved in the annotation effort to scale up to the rate of data generation.
  • The Long Tail is a prolific source of content 7 Short Head Long Tail Content produced Contributors (sorted) News : Video: Product reviews: Food reviews: Talent judging: Newspapers TV/Hollywood Consumer reports Food critics Olympics Blogs YouTube Amazon reviews Yelp American Idol
  • Wikipedia is reasonably accurate 8
  • Wikipedia has breadth and depth 9 http://en.wikipedia.org/wiki/Wikipedia:Size_comparisons, July 2008 Articles Words (millions) Wikipedia Britannica Online
  • 10 We can harness the Long Tail of scientists to directly participate in the gene annotation process.
  • From crowdsourcing to structured data 11 The Gene Wiki Citizen Science
  • Filtering, extracting, and summarizing PubMed Documents Concepts Review article
  • Filtering, extracting, and summarizing PubMed Documents Concepts
  • Wiki success depends on a positive feedback 14 Gene wiki page utility Number of users Number of contributors 1001 2002
  • 10,000 gene stubs within Wikipedia 15 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 Utility Users Contributors
  • Gene Wiki has a critical mass of readers 16 Total: 4.0 million views / month Huss, PLoS Biol, 2008; Good, NAR, 2011 Utility Users Contributors
  • Gene Wiki has a critical mass of editors 17 Increase of ~10,000 words / month from >1,000 edits Currently 1.42 million words Approximately equal to 230 full-length articles Good, NAR, 2011 Utility Users Contributors Editorcount Editors Edits Editcount
  • A review article for every gene is powerful 18 References to the literature Hyperlinks to related concepts Reelin: 98 editors, 703 edits since July 2002 Heparin: 358 editors, 654 edits since June 2003 AMPK: 109 editors, 203 edits since March 2004 RNAi: 394 editors, 994 edits since October 2002
  • Making the Gene Wiki more computable 19 Structured annotationsFree text
  • Filling the gaps in gene annotation 20 Wikilink GO exact match Gene Wiki mapping NCBI Entrez Gene: 334 Candidate assertion GO:0006897 6319 novel GO annotations 2147 novel DO annotations
  • Gene Wiki content improves enrichment analysis 23 p-value (PubMed only) p-value (PubMed + GW) Muscle contraction More significant PubMed + GW More significant PubMed only Good BM et al., BMC Genomics, 2011
  • Making the Gene Wiki more computable 24 Structured annotationsFree text Analyses
  • Expansion through outreach and incentives 26 SP-A1 SP-A2 KIF11 LIG3 MIR155 EPHX2
  • Cardiovascular Gene Wiki Portal 27 CAMK2D -- CaM kinase II subunit delta CSRP3 -- Cysteine and glycine-rich protein 3 GJA1 -- Gap junction alpha-1 protein / Connexin-43 MAPK14 -- Mitogen-activated protein kinase 14 / p38- MYL7 -- Myosin regulatory light chain 2, atrial isoform MYL2 -- Myosin regulatory light chain 2, ventricular/cardiac isoform PECAM1 -- Platelet endothelial cell adhesion molecule/CD31 RYR2 -- Ryanodine receptor 2 ATP2A2 -- Sarcoplasmic/endoplasmic reticulum calcium ATPase 2 / SERCA2 TNNI3 -- Troponin I, cardiac muscle TNNT2 -- Troponin T, cardiac muscle Peipei Ping UCLA
  • The Long Tail of scientists is a valuable source of information on gene function 28
  • From crowdsourcing to structured data 29 The Gene Wiki Citizen Science
  • Gene databases are numerous and overlapping 30 and hundreds more
  • Why is there so much redundancy? 31 Users Requests Resources Time Community development BioGPS emphasizes community extensibility
  • Why do developers define the gene report view? 32 BioGPS emphasizes user customizability
  • http://biogps.org Community extensibility and user customizability 33
  • Utility UsersContributors Utility: A simple and universal plugin interface 34
  • Utility UsersContributors Utility: A simple and universal plugin interface 35
  • Utility UsersContributors Utility: A simple and universal plugin interface 36
  • Utility UsersContributors Utility: A simple and universal plugin interface 37
  • Utility UsersContributors Utility: A simple and universal plugin interface 38
  • Utility: A simple and universal plugin interface 39 Utility UsersContributors Total of > 540 gene-centric online databases registered as BioGPS plugins
  • Users: BioGPS has critical mass 40 > 6400 registered users 14,000 unique visitors per month 155,000 page views per month 1. Harvard 2. NIH 3. UCSD 4. Scripps 5. MIT 6. Cambridge 7. U Penn 8. Stanford 9. Wash U 10. UNC Top 10 organizations Daily pageviewsUtility UsersContributors
  • Contributors: Explicit and implicit knowledge 41 540 plugins registered (>300 publicly shared) by over 120 users spanning 280+ domains Utility UsersContributors
  • Gene Annotation Query as a Service 42 http://mygene.info High performance 3M hits/month Highly scalable 13k species 16M genes Weekly data updates JSON output REST interface Python/R/JS libraries
  • The Long Tail of bioinformaticians can collaboratively build a gene portal. 43
  • From crowdsourcing to structured data 44 The Gene Wiki Citizen Science
  • The biomedical literature is growing fast 45 0 200,000 400,000 600,000 800,000 1,000,000 1,200,000 1983 1988 1993 1998 2003 2008 2013 Number of new PubMed-indexed articles
  • Information Extraction 46 1. Find mentions of high level concepts in text 2. Map mentions to specific terms in ontologies 3. Identify relationships between concepts
  • Disease mentions in PubMed abstracts 47 NCBI Disease corpus 793 PubMed abstracts (100 development, 593 training, 100 test) 12 expert annotators (2 annotate each abstract) 6,900 disease mentions Doan, Rezarta, and Zhiyong Lu. "An improved corpus of disease mentions in PubMed citations." Proceedings of the 2012 Workshop on Biomedical Natural Language Processing. Association for Computational Linguistics.
  • Four types of disease mentions 48 Specific Disease: Diastrophic dysplasia Disease Class: Cancers Composite Mention: prostatic , skin , and lung cancer Modifier: ..the familial breast cancer gene , BRCA2.. Doan, Rezarta, and Zhiyong Lu. "An improved corpus of disease mentions in PubMed citations." Proceedings of the 2012 Workshop on Biomedical Natural Language Processing. Association for Computational Linguistics.
  • Question: Can a group of non-scientists collectively perform concept recognition in biomedical texts? 49
  • The Turk 50 http://en.wikipedia.org/wiki/The_Turk
  • The Turk 51 http://en.wikipedia.org/wiki/The_Turk
  • Amazon Mechanical Turk (AMT) 52 Requester Amazon For each task, specify: a qualification test how many workers per task how much we will pay per task Manages: parallel execution of jobs worker access to tasks via qualification tests payments task advertising Workers 1. Create tasks 2. Execute 3. Aggregate
  • Instructions to workers 53 Highlight all diseases and disease abbreviations ...are associated with Huntington disease ( HD )... HD patients received... The Wiskott-Aldrich syndrome ( WAS ) , an X-linked immunodeficiency Highlight the longest span of text specific to a disease ... contains the insulin-dependent diabetes mellitus locus Highlight disease conjunctions as single, long spans. ... a significant fraction of familial breast and ovarian cancer , but undergoes Highlight symptoms - physical results of having a disease XFE progeroid syndrome can cause dwarfism, cachexia, and microcephaly. Patients often display learning disabilities, hearing loss, and visual impairment.
  • Qualification test 54 Test #1: Myotonic dystrophy ( DM ) is associated with a ( CTG ) in trinucleotide repeat expansion in the 3-untranslated region of a protein kinase-encoding gene , DMPK , which maps to chromosome 19q13 . 3 . Test #2: Germline mutations in BRCA1 are responsible for most cases of inherited breast and ovarian cancer . However , the function of the BRCA1 protein has remained elusive . As a regulated secretory protein , BRCA1 appears to function by a mechanism not previously described for tumour suppressor gene products. Test #3: We report about Dr . Kniest , who first described the condition in 1952 , and his patient , who , at the age of 50 years is severely handicapped with short stature , restricted joint mobility , and blindness but is mentally alert and leads an active life . This is in accordance with molecular findings in other patients with Kniest dysplasia and 26 yes / no questions
  • Qualification test results 55 Threshold for passing 33/194 passed 17% Workers qualified workers
  • Simple annotation interface 56 Click to see instructions Highlight disease mentions
  • Experimental design Task: Identify the disease mentions in the 593 abstracts from the NCBI disease corpus $0.06 per Human Intelligence Task (HIT) HIT = annotate one abstract from PubMed 5 workers annotate each abstract 57
  • This molecule inhibits the growth of a broad panel of cancer cell lines, and is particularly efficacious in leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) patient tumor samples. Thus, inhibition of CDK9 may represent an interesting approach as a cancer therapeutic target especially in hematologic malignancies. This molecule inhibits the growth of a broad panel of cancer cell lines, and is particularly efficacious in leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) patient tumor samples. Thus, inhibition of CDK9 may represent an interesting approach as a cancer therapeutic target especially in hematologic malignancies. Aggregation function based on simple voting 58 5 1 or more votes (K=1) This molecule inhibits the growth of a broad panel of cancer cell lines, and is particularly efficacious in leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) patient tumor samples. Thus, inhibition of CDK9 may represent an interesting approach as a cancer therapeutic target especially in hematologic malignancies. K=2 K=3 K=4 This molecule inhibits the growth of a broad panel of cancer cell lines, and is particularly efficacious in leukemia cells, including orthotopic leukemia preclinical models as well as in ex vivo acute myeloid leukemia (AML) and chronic lymphocytic leukemia (CLL) patient tumor samples. Thus, inhibition of CDK9 may represent an interesting approach as a cancer therapeutic target especially in hematologic malignancies.
  • Comparison to gold standard 59 F = 0.81, k = 2, N = 5 593 documents 7 days 17 workers $192.90
  • Comparisons to text-mining algorithms 64
  • ...