1. Pescadillo affects rRNA Processing which may affect the S Phase, since the WDR12 Gene affects Cell Physiology with which rRNA Processing coexists.2 However, the S Phase or synthesis phase of the cell cycle is also a process of Aneuploidy which has negatively effect on cell growth. 3. Since DNA replication is known to occur between he G1 and G2 phases of the S Phase, mutations of Pescadillo could lead to G1 Phase arrest thereby showing growth arrest. 4. By confirmation in the text, a specific temperature sensitive mutant experiences this condition.
48th ACM Southeast Conference. ACMSE 2010.Oxford, Mississippi. April 15-17, 2010. Semantic Predications for Complex Information Needs in Biomedical Literature Delroy Cameron, RamakanthKavuluru, Pablo N. Mendes AmitP. Sheth, KrishnaprasadThirunarayan Ohio Center for Excellence in Knowledge-enabled Computing kno.e.sisCenter, Wright State University Dayton, OH 45435, USA Olivier Bodenreider National Library of Medicine Bethesda, MD 20894, USA 2011 International Conference on Bioinformatics and Biomedicine (BIBM) 12-15 November, 2011 Atlanta, Georgia
MOTIVATION • Information Retrieval Interaction Sequence – Keyword Search – Document Selection – Document Inspection – Query Reformulation Exploratory Search Document-Centric Model – Hyperlink-driven Browsing – Information is within Documents Limitations – Query Reformulation – Constrained Navigation 2
“How do mutations in the Presenilin-1 (PS1) gene affect Alzheimer’s disease (AD)?” PS1 associated_withAlzheimer’s Disease . . . mutations in PS1 lead to Alzheimer’s disease by increasing the extracellular levels of [amyloid peptide 42] A42. (Source: PMID10652366) Semantic Predications . . . familial early onset Alzheimer’s disease is caused by point mutations in the amyloid precursor protein gene on chromosome 21, in the presenilin 2(PS2)1 gene on chromosome 1, or, most frequently, in the presenilin chromosome14 finding_site_ofpresenilin1 1(PS1) gene on chromosome14. . . (Source:PMID9013610)
COMPLEX INFO NEEDS Literature-Based Discovery (LBD) Don R. Swanson’s Hypotheses o Raynaud’s Syndrome-Dietary Fish Oil o Magnesium-Migraine Question Answering Text REtrieval Conference (TREC) 2006, 28 questions TREC Genomics Track - http://ir.ohsu.edu/genomics/ 6
REACHABILITY “the notion of being able to get from one vertex in a directed graph to some other vertex” Labeled Graph Calcium Channel Blocker ISA a INVERSE_ISA Magnesium b c 8
REACHABILITY-DOCS “is the notion of being able to cover the documents in a document set, usingthe vertices in a directed graph from one vertex to some other vertex” Predications Graph Plane Document Plane 9
11Knowledge Abstraction • Stopping Conditions C0007613 – Cell physiology – No Reachable Docs in PG – No Successors in PG +Reachable Docs in DP – No Successors in PG + No Reachable Docs in DP coexists_with coexists_with C1261468 - Cell fusion C0040682 - cell transformation Predications Graph Plane Document Plane
DATASET • TREC 2006 Corpus 26 Questions 162,259 full text documents 12,641,116 text items Gold Standard 1381 Gold Standard Documents 3461 Text items •Biomedical Knowledge Repository (BKR) 13 million from UMLS Metathesaurus 8 million from Literature using SemRep TREC Genomics Track - http://ir.ohsu.edu/genomics/ 13
OBSERVATIONS Absence of predications in text Predication extraction methods (SemRep) Absence of direct connections among text item Ambiguity in written language Abstractions may lead to information overflow Quality of background knowledge 17
“How do mutations in the Pes gene affect cell growth?” DNA Replication G1_phase G2_phase
CONCLUSION • Novel Knowledge-driven framework • Semantic Predications to link scientific content • Alternative to Query reformulation • Background knowledge boost recall • Effective at Coarse granularity • Poor at fine granularity 19
ACKNOWLEDGEMENT National Library of Medicine (NIH/NLM) Human Performance & Cognition Ontology Project @knoesis CarticRamakrishnan Michael Cooney Gary Alan Smith Paul Fultz II Jeffrey Ali Hyacinthe Thomas C. Rindflesch Mohamed Cyclegar Dongwook Shin John Nguyen May Cheh 21
TREC Genomics Track 2006 (Questions) Topic ID Question 160 What is the role of PrnP in mad cow disease? 161 What is the role of IDE in Alzheimers disease 163 What is the role of APC (adenomatouspolyposis coli) in colon cancer? 165 How do Cathepsin D (CTSD) and apolipoprotein E (ApoE) interactions contribute to Alzheimers disease? 167 How does nucleoside diphosphatekinase (NM23) contribute to tumor progression? 168 How does BARD1 regulate BRCA1 activity? 169 How does APC (adenomatouspolyposis coli) protein affect actin assembly 170 How does COP2 contribute to CFTR export from the endoplasmic reticulum? 172 How does p53 affect apoptosis? 173 How do alpha7 nicotinic receptor subunits affect ethanol metabolism? 174 How does BRCA1 ubiquitinating activity contribute to cancer? 176 How does Sec61-mediated CFTR degradation contribute to cystic fibrosis? 177 How do Bop-Pes interactions affect cell growth? 178 How do interactions between insulin-like GFs and the insulin receptor affect skin biology? 179 How do interactions between HNF4 and COUP-TF1 suppress liver function? 180 How do Ret-GDNF interactions affect liver development? 184 How do mutations in the Pes gene affect cell growth? 185 How do mutations in the hypocretin receptor 2 gene affect narcolepsy? 186 How do mutations in the Presenilin-1 gene affect Alzheimers disease?
24Most Relevant Subtree a Level-0 Level-1 Level-2 Level-3 Level-4