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EECS 730 Introduction to Bioinformatics Function. Luke Huan Electrical Engineering and Computer Science http://people.eecs.ku.edu/~jhuan/. Overview. Gene ontology Challenges What is gene ontology construct gene ontology - PowerPoint PPT Presentation
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EECS 730Introduction to Bioinformatics
Function
Luke HuanElectrical Engineering and Computer Science
http://people.eecs.ku.edu/~jhuan/
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Overview
Gene ontology
Challenges
What is gene ontology
construct gene ontology
Text mining, natural language processing and
information extraction: An Introduction
Summary
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Ontology <philosophy> A systematic account of Existence. <artificial intelligence> (From philosophy) An explicit formal specification
of how to represent the objects, concepts and other entities that are assumed to exist in some area of interest and the relationships that hold among them.
<information science> The hierarchical structuring of knowledge about things by subcategorising them according to their essential (or at least relevant and/or cognitive) qualities.
This is an extension of the previous senses of "ontology" (above) which has become common in discussions about the difficulty of maintaining subject indices.
The philosophy of indexing everything in existence?
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Aristotele’s (384-322 BC) Ontology Substance
plants, animals, ... Quality Quantity Relation Where When Position Having Action Passion
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Ontology and -informatics
In information sciences, ontology is better defined as: “a domain of knowledge, represented by facts and their logical connections, that can be understood by a computer”.
(J. Bard, BioEssays, 2003)
“Ontologies provide controlled, consistent vocabularies to describe concepts and relationships, thereby enabling knowledge sharing”
(Gruber, 1993)
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Information Exchange in Bio-sciences
Basic challenges: Definition, definition, definition
What is a name? What is a function?
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Cell
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Cell
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Cell
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Cell
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Cell
Image from http://microscopy.fsu.edu
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What’s in a name?
The same name can be used to describe different concepts
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What’s in a name?
Glucose synthesis Glucose biosynthesis Glucose formation Glucose anabolism Gluconeogenesis
All refer to the process of making glucose from simpler components
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What’s in a name?
The same name can be used to describe different concepts
A concept can be described using different names
Comparison is difficult – in particular across species or across databases
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Function (what) Process (why)
Drive nail (into wood) Carpentry
Drive stake (into soil) Gardening
Smash roach Pest Control
Clown’s juggling object Entertainment
What is Function? The Hammer Example
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Information Explosion
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Entering the Genome Sequencing Era
Eukaryotic Genome Sequences Year Genome # GenesSize (Mb)
Yeast (S. cerevisiae) 1996 12 6,000
Worm (C. elegans) 1998 97 19,100
Fly (D. melanogaster) 2000 120 13,600
Plant (A. thaliana) 2001 125 25,500
Human (H. sapiens, 1st Draft) 2001 ~3000 ~35,000
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A Common Language for Annotation of Genes from
Yeast, Flies and Mice
What is the Gene Ontology?
…and Plants and Worms
…and Humans
…and anything else!
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http://www.geneontology.org/
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What is the Gene Ontology?
Gene annotation system
Controlled vocabulary that can be applied to all organisms Organism independent
Used to describe gene products proteins and RNA - in any organism
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Molecular Function = elemental activity/task the tasks performed by individual gene products; examples
are carbohydrate binding and ATPase activity
Biological Process = biological goal or objective broad biological goals, such as mitosis or purine
metabolism, that are accomplished by ordered assemblies of molecular functions
Cellular Component = location or complex subcellular structures, locations, and macromolecular
complexes; examples include nucleus, telomere, and RNA polymerase II holoenzyme
The 3 Gene Ontologies
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Cellular Component where a gene product acts
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Cellular Component
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Cellular Component
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Cellular Component
Enzyme complexes in the component ontology refer to places, not activities.
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Molecular Function
insulin binding
insulin receptor activity
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Molecular Function activities or “jobs” of a gene product
glucose-6-phosphate isomerase activity
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Molecular Function
A gene product may have several functions; a function term refers to a single reaction or activity, not a gene product.
Sets of functions make up a biological process.
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Biological Processa commonly recognized series of events
cell division
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Biological Process
transcription
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Biological Process
Metabolism: degradation or synthesis of biomelecules
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Biological Process
Development: how a group of cell become a tissue
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Biological Process
social behavior
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Ontology applications
Can be used to: Formalise the representation of biological knowledge Standardise database submissions Provide unified access to information through
ontology-based querying of databases, both human and computational
Improve management and integration of data within databases.
Facilitate data mining
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Gene Ontology Structure
Ontologies can be represented as directed acyclic graphs (DAG), where the nodes are connected by edges Nodes = terms in biology Edges = relationships between the terms
is-a part-of
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Parent-Child Relationships
Chromosome
Cytoplasmic chromosome
Mitochondrialchromosome
Plastid chromosome
Nuclear chromosome
A child is a subset or instances of
a parent’s elements
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Parent-Child Relationshipscell
membrane chloroplast
mitochondrial chloroplastmembrane membrane
is-apart-of
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Annotation in GO
A gene product is usually a protein but can be a functional RNA
An annotation is a piece of information associated with a gene product
A GO annotation is a Gene Ontology term associated with a gene product
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Terms, Definitions, IDs Term: MAPKKK cascade (mating sensu Saccharomyces)
Goid: GO:0007244
Definition: OBSOLETE. MAPKKK cascade involved in transduction of mating pheromone signal, as described in Saccharomyces.
Evidence code: how annotation is done
Definition_reference: PMID:9561267
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Annotation Example
GO Term
Gene Product
nek2
centrosomeGO:0005813
Reference
PMID: 11956323
Evidence Code
IDAInferred fromDirect Assay
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GO Annotation
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GO Annotation
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GO Annotation
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Evidence Code
Indicate the type of evidence in the cited source that supports the association between the gene product and the GO term
http://www.geneontology.org/GO.evidence.html
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Types of evidence codes
Types of evidence code Experimental codes - IDA, IMP, IGI, IPI, IEP Computational codes - ISS, IEA, RCA, IGC Author statement - TAS, NAS Other codes - IC, ND
Two types of annotation Manual Annotation Electronic Annotation
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Beyond GO – Open Biomedical Ontologies
Orthogonal to existing ontologies to facilitate combinatorial approaches Share unique identifier space Include definitions
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Gene Ontology and Text Mining
Derive ontology from text data More general goal: understand text data
automatically
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Finding GO terms
In this study, we report the isolation and molecular characterization of the B. napus PERK1 cDNA, that is predicted to encode a novel receptor-like kinase. We have shown that like other plant RLKs, the kinase domain of PERK1 has serine/threonine kinase activity, In addition, the location of a PERK1-GTP fusion protein to the plasma membrane supports the prediction that PERK1 is an integral membrane protein…these kinases have been implicated in early stages of wound response…
Process: response to wounding GO:0009611
Function: protein serine/threonine kinase activity GO:0004674
Component: integral to plasma membrane GO:0005887
…for B. napus PERK1 protein (Q9ARH1)
PubMed ID: 12374299
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Mining Text DataData Mining / Knowledge Discovery
Structured Data Multimedia Free Text Hypertext
HomeLoan ( Loanee: Frank Rizzo Lender: MWF Agency: Lake View Amount: $200,000 Term: 15 years)
Frank Rizzo boughthis home from LakeView Real Estate in1992. He paid $200,000under a15-year loanfrom MW Financial.
<a href>Frank Rizzo</a> Bought<a hef>this home</a>from <a href>LakeView Real Estate</a>In <b>1992</b>.<p>...Loans($200K,[map],...)
(Taken from ChengXiang Zhai, CS 397cxz, UIUC, CS – Fall 2003)
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Bag-of-Tokens Approaches
Four score and seven years ago our fathers brought forth on this continent, a new nation, conceived in Liberty, and dedicated to the proposition that all men are created equal. Now we are engaged in a great civil war, testing whether that nation, or …
nation – 5civil - 1war – 2men – 2died – 4people – 5Liberty – 1God – 1…
FeatureExtraction
Loses all order-specific information!Severely limits context!
Documents Token Sets
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Natural Language Processing
A dog is chasing a boy on the playgroundDet Noun Aux Verb Det Noun Prep Det Noun
Noun Phrase Complex Verb Noun PhraseNoun Phrase
Prep PhraseVerb Phrase
Verb Phrase
Sentence
Dog(d1).Boy(b1).Playground(p1).Chasing(d1,b1,p1).
Semantic analysis
Lexicalanalysis
(part-of-speechtagging)
Syntactic analysis(Parsing)
A person saying this maybe reminding another person to
get the dog back…
Pragmatic analysis(speech act)
Scared(x) if Chasing(_,x,_).+
Scared(b1)
Inference
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General NLP—Too Difficult! Word-level ambiguity
“design” can be a noun or a verb (Ambiguous POS) “root” has multiple meanings (Ambiguous sense)
Syntactic ambiguity “natural language processing” (Modification) “A man saw a boy with a telescope.” (PP Attachment)
Anaphora resolution “John persuaded Bill to buy a TV for himself.”
(himself = John or Bill?) Presupposition
“He has quit smoking.” implies that he smoked before.
Humans rely on context to interpret (when possible).This context may extend beyond a given document!
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Reference for GO
Gene ontology teaching resources: http://www.geneontology.org/
GO.teaching.resources.shtml
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References for Text Ming
1. C. D. Manning and H. Schutze, “Foundations of Natural Language Processing”, MIT Press, 1999.
2. S. Russell and P. Norvig, “Artificial Intelligence: A Modern Approach”, Prentice Hall, 1995.
3. S. Chakrabarti, “Mining the Web: Statistical Analysis of Hypertext and Semi-Structured Data”, Morgan Kaufmann, 2002.
4. G. Miller, R. Beckwith, C. FellBaum, D. Gross, K. Miller, and R. Tengi. Five papers on WordNet. Princeton University, August 1993.
5. C. Zhai, Introduction to NLP, Lecture Notes for CS 397cxz, UIUC, Fall 2003.
6. M. Hearst, Untangling Text Data Mining, ACL’99, invited paper. http://www.sims.berkeley.edu/~hearst/papers/acl99/acl99-tdm.html
7. R. Sproat, Introduction to Computational Linguistics, LING 306, UIUC, Fall 2003.
8. A Road Map to Text Mining and Web Mining, University of Texas resource page. http://www.cs.utexas.edu/users/pebronia/text-mining/
9. Computational Linguistics and Text Mining Group, IBM Research, http://www.research.ibm.com/dssgrp/
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Acknowledge
Some slides are taken from http://www.tulane.edu/~wiser/cells/.
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