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SolrSherlock: Linkfinding among Biomolecules with Literature-based Discovery
The document discusses the potential link between the HFE gene, associated with hereditary hemochromatosis, and the BCR-ABL fusion, linked to chronic myelogenous leukemia. Evidence suggests that the HFE C282Y mutation could have a protective role against chronic myeloproliferative disease (CMPD). It also outlines a framework for literature-based discovery in biology, utilizing a concept called 'hypermembrane' to organize relationships from literature into an associative structure.
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SolrSherlock: Linkfinding among Biomolecules with Literature-based Discovery
- 1. HFE & BCR-ABL InSearch of Links © 2014, TopicQuests Foundation Licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 3.0 Unported License. Jack Park BigData Science Meetup Freemont, CA: 17 May, 2014 Shyam Sarkar, Organizer
- 2. Target Benefits • SolrSherlockwill support: – Hypothesis formation – Research/Experiment planning – Deep Question Answering • Personal medical issues • … “Therefore psychologically we must keep all the theories in our heads, and every theoretical physicist who is any good knows six or seven different theoretical representations for exactly the same physics.” ―Richard Feynman “Why, sometimes I've believed as many as six impossible things before breakfast.” ―The Queen: Through The Looking Glass
- 3. What We HaveRead: HFE • Human hemochromatosis protein also known as the HFE protein is a protein which in humans is encoded by the HFE gene. The HFE gene is located on short arm of chromosome 6 at location 6p22.2* – Some mutations which are associated with Hereditary Hemochromatosis (a genetic disease)**: • C282Y • H63D *http://en.wikipedia.org/wiki/HFE_%28gene%29 **http://www.genome.gov/10001214
- 4. What We HaveRead: BCR-ABL aka: Philadelphia Chromosome • Philadelphia chromosome or Philadelphia translocation is a specific chromosomal abnormality that is associated with chronic myelogenous leukemia (CML). It is the result of a reciprocal translocation between chromosome 9 and 22, and is specifically designated t(9;22)(q34;q11)* *http://en.wikipedia.org/wiki/Philadelphia_chromosome
- 5. Are HFE andBCR-ABL Linked? • One document instance which suggests they are linked: – “We found that HFE C282Y might be associated with a protective role against CMPD. Because chronic iron deficiency or latent anemia may trigger disease susceptibility for CMPD, HFE C282Y positivity may be a genetic factor influencing this effect.”* • Note: this response is simply evidence of a link, a signal; it leaves open many questions CMPD: Chronic Myeloproliferative Disease * http://www.ncbi.nlm.nih.gov/pubmed/19258483
- 6. Where do wego from here? • We have read about some actors • We seek evidence for relationships between those actors • We have one small piece of evidence • We turn to Literature-based Discovery (LBD) – Read and process many papers – Assemble an evidence field – Determine answers and confidence levels
- 7. Sensemaking In BiologicalResearch http://www.biomedcentral.com/content/pdf/1471-2105-15-117.pdf Figure 1 © 2014 Mirel and Görg; licensee BioMed Central Ltd (cc by)
- 8. Literature-based Discovery • Swanson’sABC Model • Two Varieties of LBD – Closed Discovery – Open Discovery
- 9. SolrSherlock Block Level •Models – Process Models – Conceptual Graphs – OpenBEL • Identity – Topic Map • Topics • Relations • Associations – Bayes – DeepLearning – HyperMembrane • Interface Interface Associations Identity Models Data
- 10. SolrSherlock’s HyperMembrane • SolrSherlockBig Picture – Documents to harvest – Sentences to parse • WordGrams from the sentences – Lenses to interpret the sentences » NTuples from the WordGrams – Lenses to interpret whole documents • HyperMembrane as a fabric woven from the Ntuples – Organizes statements read from literature into a kind of associative fabric, linked into a topic map
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- 13. Sentence Parse • SalientWordGrams in that sentence: – C282Y – might be associated with a – protective role against • Transforms to: protect against – CMPD We found that HFE C282Y might be associated with a protective role against CMPD +-----------------MVp-----------------------------------+ | +---------Js------------+ | +---Cet------+ | | +-------Ds---------+ | +-Sp-+--TH--+ +--G-+--Ss--+--Ix---+---Pv-----+---MVp--+ | +----A---+ +--Js--+ | | | | | | | | | | | | | | we found.p that.c HFE C282Y might.v be.v associated.v with a protective.a role.n against CMPD Parse produced by a Java implementation of Link Grammar Parser
- 14. WordGram instances created whileprocessing the sentence WordGram Example • Sentence: – CO2 causes climate change • WordGrams – Terminals • CO2 • causes • climate • Change – Pairs • CO2 causes • causes climate • climate change – Triples • CO2 causes climate • causes climate change – Quads • CO2 causes climate change • Parsed Result—representation of the sentence: – CO2 (terminal, noun) – cause (terminal, verb, transformed causescause) – climate change (pair, noun phrase) • Resulting NTuple – {CO2, cause, climate change} • Where the names are replaced with topic locators from the topic map These WordGram instances represent the sentence; they are wired into the fabric. This Ntuple participates in high-level structure formation and in question answering WordGram instances created while processing the sentence WordGram instances created while processing the sentence WordGram instances created while processing the sentence
- 15. Lenses • Simple Interpreters –Based on Canonical Predicates – Build structures from parsed sentences and WordGrams – Examples from biology • Cause • Bind • Augment • Prevent • Increase • Decrease • Believe
- 16. Multiple Lenses • Considerthis sentence: – We believe that A causes B – Two Lenses in play • Believe • Cause – Result is a nested NTuple • {We, believe, {A, cause, B}}
- 17. Canonical Predicate • Resultsfrom transformations on predicates – E.g. • A causes B, A can cause B, A will cause B A cause B • A is caused by B B cause A
- 18. Actors: Named Entities •For any given named entity, there will be one and only one WordGram – Issue of Ambiguity • Same name string can serve different topics in the topic map – Topic map maintains identity for disambiguation • Thus, a single WordGram might be associated with more than one individual actor • This means: – Fibers (threads) flowing through the fabric must be maintained in bundles according to their context (topic)
- 19. Lens Selection andAction • The Lens: – ProtectAgainst • Selected by the WordGram for “protect against” – Is a transformation of the WordGram for “protective role against” • Lens Action: – Create an NTuple • {C282Y, protect against, CMPD} • We will call that NTuple an Assertion We found that HFE C282Y might be associated with a protective role against CMPD
- 20. Weaving an InformationFabric • Background: – One and only one WordGram for each Actor (named entity) – One and only one WordGram for each canonical Predicate – One and only one NTuple for each Assertion • WordGrams which form an NTuple are strung together as beads on a string in the fabric. – Thus, it is the detection of NTuple structures (Assertions) which form the HyperMembrane’s fabric. Note: it is next to impossible to diagram the fabric, but it will likely look like a very tangled knotted structure. https://www.flickr.com/photos/fermicat/27 3539481/in/set-72157601620157588/
- 21. Fabric Example • TwoNTuples – {Jack Park, AuthoredBook, The Wind Power Book} – {Jack Park, AuthoredBook, Ohio State University Football Vault} JP101 JP102 Book101 AuthoredBook Wind Power Book OSU Football… Book102 Jack Park Topic Map organizes fiber bundles
- 22. Looking Forward • Lenses,today, are hardwired – Opportunity for adaptive learning of new lenses • Fabric, today, is simple – Opportunity to use cardinalities, frequency counts in the fabric for: • Probabilistic modeling • Topological studies • Opportunity for a Domain-Specific Language (DSL) to emerge
- 23. Completed Representation antioxidants kill free radicals Contraindicates macrophagesuse free radicals to kill bacteria Bacterial Infection Antioxidants Because Appropriate For Compromised Host Let us co-create Cognitive Agents for Discovery jackpark@topicquests.org Thanks to Mei Lin Fung, David Alexander Price, and Patrick Durusau for valuable comments SolrSherlock at: http://debategraph.org/SolrSherlock and https://github.com/SolrSherlock