finding biologically relevant information using adios thaibinh’s final project for cbb545: april...
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Finding biologically relevant information using ADIOS
ThaiBinh’s final project for CBB545:
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:S S + SS 1S a
A possible derivation:SS + SS + S + S1 + S + S1 + 1 + S1 + 1 + a
A very quick primer on grammars
• We can visualize the expansion as a tree, and read the leaves
The grammar:S S + SS 1S a
A possible derivation:SS + SS + S + S1 + S + S1 + 1 + S1 + 1 + a
S
S S
S S1
1 a
+
+
A very quick primer on grammars
• We can visualize the expansion as a tree, and read the leaves
S
S S
S S1
1 a
+
+
The grammar:S S + SS 1S a
A possible derivation:SS + SS + S + S1 + S + S1 + 1 + S1 + 1 + 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 grammarP18 (a,presentation) P19 (E20,has,P18)E20 {Hugo,Laura,ThaiBinh}P21 (Chong,had)P22 (in,CBB545)P23 (P19,P22)P24 (P21,P18)
P18 (a,presentation) P19 (E20,has,P18)E20 {Hugo,Laura,ThaiBinh}P21 (Chong,had)P22 (in,CBB545)P23 (P19,P22)P24 (P21,P18)
P18 (a,presentation) P19 (E20,has,P18)E20 {Hugo,Laura,ThaiBinh}P21 (Chong,had)P22 (in,CBB545)P23 (P19,P22)P24 (P21,P18)
(P19,P22)
(E20,has,P18)
{Hugo,Laura,ThaiBinh}
(a,presentation) (in,CBB545)
P18 (a,presentation) P19 (E20,has,P18)E20 {Hugo,Laura,ThaiBinh}P21 (Chong,had)P22 (in,CBB545)P23 (P19,P22)P24 (P21,P18)
(P21,P18)
(Chong,had)
(a,presentation)
P18 (Chong,had,a) P19 (has,a)P20 (E21,P19,presentation)E21 {Hugo,Laura,ThaiBinh}P22 (in,CBB545) P23 (P20,P22) P24 (P18,presentation)
P18 (Chong,had,a) P19 (has,a)P20 (E21,P19,presentation)E21 {Hugo,Laura,ThaiBinh}P22 (in,CBB545) P23 (P20,P22) P24 (P18,presentation)
P18 (a,presentation) P19 (E20,has,P18)E20 {Hugo,Laura,ThaiBinh}P21 (Chong,had)P22 (in,CBB545)P23 (P19,P22)P24 (P21,P18)
Two different grammars: Same end result
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)
AbnerFind mentions of genes
“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]
MetamapFind mentions of diseases
The Project: Input
• Replace any mention of a gene with a generic term
• Ex.
GeneOne antagonizes GeneTwo signaling in the nucleus
Smad7 antagonizes TGF-{beta} signaling in the nucleus
GeneOne negatively regulates expression of GeneTwo
PTEN negatively regulates expression of cyclin D1
The Project: Input
• Replace any mention of a gene/disease with a generic term
• Ex.p16 is consistently expressed in endometrial tubal metaplasia
The expression of cyclin D1 is more often correlated with prognosis in cancers of ampulla of vater
GeneOne is consistently expressed in DiseaseOne
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 GeneTwoantagonizes
negatively regulates
GeneOnez GeneTwoincreases transcription
positively regulates
GeneOne GeneTwo
GeneOnez GeneTwo
“Tagging” the patterns
GeneOne GeneTwoantagonizes
negatively regulates
GeneOnez GeneTwoincreases transcription
positively regulates
GeneOne GeneTwo
GeneOnez GeneTwo
“Tagging” the patterns
GeneOne GeneTwo
antagonizes
negatively regulates
inhibits
GeneOne GeneTwo
increases transcription
positively regulates
activates
Seeing a new sentence
Ras/Erk pathway positively regulates Jak1/STAT6 activity
Seeing a new sentence
GeneOne GeneTwo
increases transcription
positively regulates
activates
Ras/Erk pathway positively regulates Jak1/STAT6 activity
Seeing a new sentence
Ras/Erk Jak1/STAT6
increases transcription
positively regulates
activates
The big picture…Automatic extraction of regulation
Ras/Erk pathway positively regulates Jak1/STAT6 activity
GeneOne action GeneTwoSmad7 inhibit TGF-Beta
PTEN inhibit Cyclin D1
Ras/ERK activate Jak1/Stat6
Smad7 antagonizes TGF-{beta} signaling in the nucleus
PTEN negatively regulates expression of cyclin D1
GeneOne expression DiseaseOnep53 down-
regulatedNeck cancer
p16 upregulated Endo. tubal metaplasia
Loss of p53 Expression Correlates with… Neck Cancer
p16 is consistently expressed in endometrial 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/disease-mentions) 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/disease-mentions) are not always accurate
• Is it even feasible?– Stay tuned…