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ThaiBinh’s final project for CBB545: Finding biologically relevant information using ADIOS April 19, 2007 The current state of affairs in natural language processing • NLP: Converting human language into representations that are easier for computers to understand • Most natural language processing requires a tagged training set • Tagging = time consuming/costly http://en.wikipedia.org/wiki/Natural_language_processing http://www.ldc.upenn.edu/Catalog/CatalogEntry.jsp?catalogId=LDC99T42 http://www.ldc.upenn.edu/Catalog/CatalogEntry.jsp?catalogId=LDC99T42 ADIOS • “Unsupervised learning of natural languages” • ADIOS: Automatic distillation of structure • Input: A corpus of characters (most likely, untagged sentences) • Output: A grammar “Unsupervised learning of natural languages”, Solan, et al., PNAS vol. 102, August 2005. A very quick primer on grammars • A set of “rules” for making a “sentence” • Ex. The grammar: A possible derivation: SS+S S S+S S1 S+S+S Sa 1+S+S 1+1+S 1+1+a A very quick primer on grammars • We can visualize the expansion as a tree, and read the leaves The grammar: SS+S S1 Sa A possible derivation: S S+S S+S+S 1+S+S 1+1+S 1+1+a S S 1 + S S 1 + S a A very quick primer on grammars • We can visualize the expansion as a tree, and read the leaves The grammar: SS+S S1 Sa A possible derivation: S S+S S+S+S 1+S+S 1+1+S 1+1+a S S 1 + S S 1 + S a ADIOS • The system builds a graph using the first sentence • With each successive sentence, it tries to find overlapping “subpaths” (patterns) ADIOS • Also try to generalize the path by looking for equivalence classes • Search for patterns and equivalence classes until no new ones are found ADIOS: A quick example • Input a corpus of sentences * * * * * * * * * * * * * * * * Chong had a presentation in CBB545 # on Tuesday Chong had a presentation # next Thursday Laura has a presentation # ThaiBinh has a presentation in CBB545 # ThaiBinh has a presentation today # today ThaiBinh has a presentation # Chong had a presentation # Hugo has a presentation in CBB545 today # ThaiBinh has a presentation in CBB545 today # Laura has a presentation in CBB545 next Thursday # Hugo has a presentation today # Chong had a presentation on Tuesday # Chong had a presentation in CBB545 on Tuesday # Laura has a presentation next Thursday # in CBB545 ThaiBinh has a presentation # today ThaiBinh has a presentation in CBB545 # ADIOS: A quick example • Output is a grammar P18 P19 E20 P21 P22 P23 P24 (a,presentation) (E20,has,P18) {Hugo,Laura,ThaiBinh} (Chong,had) (in,CBB545) (P19,P22) (P21,P18) P18 P19 E20 P21 P22 P23 P24 (a,presentation) (E20,has,P18) {Hugo,Laura,ThaiBinh} (Chong,had) (in,CBB545) (P19,P22) (P21,P18) P18 P19 E20 P21 P22 P23 P24 (a,presentation) (E20,has,P18) {Hugo,Laura,ThaiBinh} (Chong,had) (in,CBB545) (P19,P22) (P21,P18) (P19,P22) (E20,has,P18) {Hugo,Laura, ThaiBinh} (a,presentation) (in,CBB545) P18 P19 E20 P21 P22 P23 P24 (a,presentation) (E20,has,P18) {Hugo,Laura,ThaiBinh} (Chong,had) (in,CBB545) (P19,P22) (P21,P18) (P21,P18) (Chong,had) (a,presentation) P18 P19 P20 E21 P22 P23 P24 (Chong,had,a) (has,a) (E21,P19,presentation) {Hugo,Laura,ThaiBinh} (in,CBB545) (P20,P22) (P18,presentation) Two different grammars: Same end result P18 P19 P20 E21 P22 P23 P24 (Chong,had,a) (has,a) (E21,P19,presentation) {Hugo,Laura,ThaiBinh} (in,CBB545) (P20,P22) (P18,presentation) P18 P19 E20 P21 P22 P23 P24 (a,presentation) (E20,has,P18) {Hugo,Laura,ThaiBinh} (Chong,had) (in,CBB545) (P19,P22) (P21,P18) ADIOS • Able to generate sentences using the grammar it created • Can test if new sentence fits one of the grammar rules • Can be applied to wide variety of domains – Bible in various languages – Classify protein function based on amino acid sequence The Project • Use ADIOS to create grammar rules from biomedical sentences • Look for gene-gene associations • Look for gene-disease associations • Infer information about a pair of genes in an unseen sentence based on its sentence structure (pattern) Abner Find mentions of genes Metamap Find mentions of diseases “The clinical effects of cortisone and ACTH (adrenocorticotropic hormone) in the collagen diseases: acute disseminated lupus erythematosus, periarteritis nodosa, dermatomyositis and scleroderma; interim report.” Phrase: "in the collagen diseases" Meta Candidates (6) 1000 C0009326:Collagen Diseases [Disease or Syndrome] Phrase: "periarteritis nodosa," Meta Candidates (4) 1000 C0031036:Periarteritis Nodosa (Polyarteritis Nodosa) [Disease or Syndrome] Phrase: "dermatomyositis" Meta Candidates (2) 1000 C0011633:Dermatomyositis [Disease or Syndrome] 1000 C0221056:Dermatomyositis (Dermatomyositis, Adult Type) [Disease or Syndrome] Phrase: "scleroderma" Meta Candidates (4) 1000 C0011644:Scleroderma [Disease or Syndrome] 1000 C0036421:Scleroderma (Systemic Scleroderma) [Disease or Syndrome] The Project: Input • Replace any mention of a gene with a generic term • Ex. Smad7 antagonizes TGF-{beta} signaling in the nucleus GeneOne antagonizes GeneTwo signaling in the nucleus PTEN negatively regulates expression of cyclin D1 GeneOne negatively regulates expression of GeneTwo The Project: Input • Replace any mention of a gene/disease with a generic term • Ex. p16 is consistently expressed in endometrial tubal metaplasia GeneOne is consistently expressed in DiseaseOne The expression of cyclin D1 is more often correlated with prognosis in cancers of ampulla of vater The expression of GeneOne is more often correlated with prognosis in DiseaseOne Let ADIOS work its “magic”… Let ADIOS work its “magic”… Out pops patterns to describe the sentences (the grammar) “Tagging” the patterns GeneOne antagonizes GeneTwo GeneOne negatively regulates GeneTwo GeneOnez increases transcription GeneTwo GeneOnez positively regulates GeneTwo “Tagging” the patterns GeneOne antagonizes GeneTwo GeneOne negatively regulates GeneTwo GeneOnez increases transcription GeneTwo GeneOnez positively regulates GeneTwo “Tagging” the patterns inhibits antagonizes GeneOne GeneTwo negatively regulates increases transcription GeneOne GeneTwo positively regulates activates Seeing a new sentence Ras/Erk pathway positively regulates Jak1/STAT6 activity Seeing a new sentence increases transcription GeneOne GeneTwo Ras/Erk pathway positively regulates Jak1/STAT6 activity positively regulates activates Seeing a new sentence increases transcription Ras/Erk Jak1/STAT6 positively regulates activates The big picture… Automatic extraction of regulation Smad7 antagonizes TGF{beta} signaling in the nucleus GeneOne action GeneTwo PTEN negatively regulates expression of cyclin D1 Smad7 inhibit TGF-Beta PTEN inhibit Cyclin D1 Ras/Erk pathway positively regulates Jak1/STAT6 activity Ras/ERK activate Jak1/Stat6 Loss of p53 Expression Correlates with… Neck Cancer p16 is consistently expressed in endometrial tubal metaplasia GeneOne expression DiseaseOne p53 downregulated Neck cancer p16 upregulated Endo. tubal metaplasia Potential (inevitable) problems • The data/sentences – Amount • ADIOS’S data usually had 1000’s of sentences – Quality • ABNER/MetaMap (used for finding gene/diseasementions) are not always accurate • Is it even feasible? – Biologists/Scientists are very creative in coming of with various ways of saying the same thing Potential (inevitable) problems • The data/sentences – Amount • ADIOS’S data usually had 1000’s of sentences – Quality • ABNER/MetaMap (used for finding gene/diseasementions) are not always accurate • Is it even feasible? – Stay tuned…