1. 1 The BioText Project Myers Seminar Sept 22, 2003 Marti Hearst Associate Professor SIMS, UC Berkeley Projected sponsored by NSF DBI-0317510, ARDA AQUAINT, and a gift from Genentech

2. 2 BioText Project Goals Provide fast, flexible, intelligent access to information for use in biosciences applications. Focus on –Textual Information –Tightly integrated with other resources Ontologies Record-based databases

3. 3 People Project Leaders: –PI: Marti Hearst Co-PI: Adam Arkin Computational Linguistics –Barbara Rosario –Presley Nakov Database Research –Ariel Schwartz –Gaurav Bhalotia (graduated) User Interface / Information Retrieval –Kevin Li –Emilia Stoica Bioscience –Dr. TingTing Zhang

4. 4 Outline Main Goals –System Architecture –Apoptosis problem statement Recent results in –Abbreviation definition recognition –Semantic relation recognition (from text) –Search User Interfaces –Hierarchical grouping of journals

5. 5 BioText: Main Goals Sophisticated Text Analysis Annotations in Database Improved Search Interface

6. 6 Recent Result (Schwartz & Hearst 03) Fast, simple algorithm for recognizing abbreviation definitions. –Simpler and faster than the rest –Higher precision and recall –Idea: Work backwards from the end Examples: –In eukaryotes, the key to transcriptional regulation of the Heat Shock Response is the Heat Shock Transcription Factor (HSF). –Gcn5-related N-acetyltransferase (GNAT) Idea: use redundancy across abstracts to figure out abbreviation meaning even when definition is not present.

7. 7 BioText: A Two-Sided Approach SwissProt Blast Mesh GO Word Net Medline Journal Full Text Sophisticated Database Design & Algorithms Empirical Computational Linguistics Algorithms

8. 8 Death Receptors Signaling Survival Factors Signaling Ca ++ Signaling P53 pathway Caspase 12 Effecter Caspases (3,6,7) Caspase 9 Apaf 1 IAPs NFkB Mitochondria Cytochrome c Bax, Bak Apoptosis Bcl-2 like BH3 only Apoptosis Network Smac ER Stress Genotoxic Stress Initiator Caspases (8, 10) AIF Lost of Attachment Cell Cycle stress, etc Slide courtesy TingTing Zhang

9. 9 The issues (courtesy TingTing Zhang): The network nodes are deduced from reading and processing of experimental knowledge by experts. Every month >1000 apoptosis papers are published. The supporting experimental data are gathered in different organs, tissues, cells using various techniques. There are various levels of uncertainty associated with different techniques used to answer certain questions. Depending on the expression patterns for the players in the network, the observation may or may not be extended to other contexts. We need to keep track of ALL the information in order to understand the system better.

10. 10 Simple cases: Mouse Bim proteins (isoforms EL, L, S) binds to human Bcl-2 (bacteriophoage screening using cDNA expression library from T-Lymphoma cell line KO52DA20). Human BimEL protein is 89% identical to mouse BimEL, Human BimL is 85% identical to mouse BimL (Hybridization of mouse bim cDNA to human fetal spleen and peripheral blood cDNA library). Bim mRNA is detected in B and T lyphoid cells (Northern blot analysis of mouse KO52DA20, WEHI 703, WEHI 707, WEHI7.1, CH1, WEHI231 WEHI415, B6.23.16BW2 cell extracts). BimL protein interact with Bcl-2 OR Bcl-XL, or Bcl-w proteins (Immuno- precipitation (anti-Bcl-2 OR Bcl-XL OR Bcl-w)) followed by Western blot (anti- EEtag) using extracts human 293T cells co-transfected with EE-tagged BimL AND (bcl-2 OR bcl-XL OR bcl-w) plasmids) BimL deleted of the BH3 domain does not bind to Bcl-2 OR Bcl-XL, or Bcl-w proteins (under experimental conditions mentioned above)

11. 11 Computational Language Goals Recognizing and annotating entities within textual documents Identifying semantic relations among entities To (eventually) be used in tandem with semi-automated reasoning systems.

12. 12 Main Ideas for NLP Approach Assign Semantics using –Statistics –Hierarchical Lexical Ontologies to generalize –Redundancy in the data Build up Layers of Representation –Syntactic and Semantic –Use these in a feedback loop

13. 13 Computational Linguistics Goals Mark up text with semantic relations

14. 14 Recent Result: Descent of Hierarchy Idea: –Use the top levels of a lexical hierarchy to identify semantic relations Hypothesis: –A particular semantic relation holds between all 2-word Noun Compounds that can be categorized by a MeSH pair.

15. 15 Definition NC: Any sequence of nouns that itself functions as a noun –asthma hospitalizations –health care personnel hand wash Technical text is rich with NCs Open-labeled long-term study of the subcutaneous sumatriptan efficacy and tolerability in acute migraine treatment.

16. 16 Identification Syntactic analysis (attachments) [Baseline [headache frequency]] [[Tension headache] patient] Our Goal: Semantic analysis Headache treatment  treatment for headache Corticosteroid treatment  treatment that uses corticosteroid NCs: Three tasks

17. 17 Main Idea: Top-level MESH categories can be used to indicate which relations hold between noun compounds headache recurrence –C23.888.592.612.441 C23.550.291.937 headache pain –C23.888.592.612.441 G11.561.796.444 breast cancer cells –A01.236 C04 A11

18. 18 Linguistic Motivation Can cast NC into head-modifier relation, and assume head noun has an argument and qualia structure. –(used-in): kitchen knife –(made-of): steel knife –(instrument-for): carving knife –(used-on): putty knife –(used-by): butcher’s knife

19. 19 Distribution of Frequent Category Pairs

20. 20 How Far to Descend? Anatomy: 250 CPs –187 (75%) remain first level –56 (22%) descend one level –7 (3%) descend two levels Natural Science (H01): 21 CPs –1 (4%) remain first level –8 (39%) descend one level –12 (57%) descend two levels Neoplasm (C04) 3 CPs: –3 (100%) descend one level

21. 21 Evaluation Apply the rules to a test set Accuracy: –Anatomy: 91% accurate –Natural Science: 79% –Diseases: 100% Total: –89.6% via intra-category averaging –90.8% via extra-category averaging

22. 22 Summary of NC Work Lexical hierarchy useful for inferring semantic relations Works because semantics are constrained and word sense ambiguity is not too much of a problem Can it be extended to other types of relations? –Preliminary results on one set of relations are promising.

23. 23 Database Research Issues Efficiently and effectively combining –Relational databases & Text –Hierarchical Ontologies –Layers of Annotations

24. 24 Interface Issues Create intuitive, appealing interfaces that are better than what’s currently out there. Start with existing assigned metadata As text analysis improves, incorporate the results into the interface.

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29. 29 Some Recent Work Organizing BioScience Journal Names –Currently there are > 3500

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32. 32 Some Recent Work Organizing BioScience Journal Names –Currently there are > 3500 Idea: –Group them into faceted hierarchies semi- automatically –Using clustering of title terms, synonym similarity via WordNet, and other techniques

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35. 35 Summary BioText aims to improve access to bioscience information via –Sophisticated language analysis –Integration of results into Annotated database Flexible user interface Eventual goal –Semi-automated mining and discovery

36. 36 There’s lots to do! biotext.berkeley.edu For more information: