BeeSpace Informatics: Interactive System for Functional Analysis

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BeeSpace InformaticsInteractive System for
Functional Analysis

• Bruce Schatz
• Institute for Genomic Biology
• University of Illinois at Urbana-Champaign
• www.beespace.uiuc.edu
• Fifth Annual Project Workshop
• IGB, Urbana IL May 22, 2009

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Concept Navigation in BeeSpace
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Informatics From Bases to Spaces

• data Bases support genome data
• e.g. FlyBase has sequences and maps
• Genes annotated by GeneOntology and
• linked to biological literature
• information Spaces support biological literature
• e.g. BeeSpace uses automatically generated
• conceptual relationships to navigate functions

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System Architecture

• BeeSpace

• Concepts

• Concepts

• SEQ

• Expressions

• Expressions

• Databases

• Bees

• Flies

• Documents

• Documents

• SEQ

• Community

• Community

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System Versions

• V1 Filter Concept Graph
• Search, Expand, Merge, Switch, Visualize
• V2 Cluster Conceptual Groupings
• Small Worlds (Natural), Language Model
  (Steerable), Concepts/Documents
• V3 Summarize Gene Descriptions
• Gene Extraction, Sentence Classification
• V4 Analyze Functional Concepts
• Concept Identification, Category Grouping
• V5 Answer Entity Relationships
• Entities, Relations, Templates

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Informatics Researchers (Faculty)

• Investigators
• Bruce Schatz, systems (Medical Information
  Science)
• ChengXiang Zhai, algorithms (Computer Science)
• Collaborators (students)
• Saurabh Sinha, Computer Science
• Jiawei Han, Computer Science
• Sheng Zhong, Bioengineering
• Nathan Price, Chemical Biomolecular Engineering
• Collaborators (advices)
• John MacMullen, Library Information Science
• Dan Roth, Computer Science
• Roxana Girju, Linguistics
• Karrie Karahalios, Computer Science

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Informatics Researchers (Staff)

• V1-V3
• Todd Littell, research programmer
• Jim Buell, research coordinator
• Nyla Ismail, biology postdoc
• Moushumi Sen Sarma, biology postdoc
• V4-V5
• David Arcoleo, research programmer
• Barry Sanders, research programmer
• Moushumi Sen Sarma, biology postdoc
• Radhika Khetani, biology postdoc

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Informatics Researchers (Students)

• V1 Filter (parse)
• Jing Jiang, Azadeh Shakery, Yuanhua Lv
• V2 Cluster (group)
• Brant Chee, Qiaozhu Mei, Peixiang Zhao
• V3 Summarize (classify)
• Xu Ling, Jing Jiang, Qiaozhu Mei, Xin He
• V4 Analyze (annotate)
• Xin He, Brant Chee, Moushumi Sarma, Xu Ling
• V5 Answer (extract)
• Xu Ling, Xin He, Yanen Li, Yue Lu

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Analysis Environment Features

• SPACE is a Paradigm not a Metaphor!
• Point of View for YOUR Problem
• Externally
• -Dynamically describe custom Region of Space
• -Merge Regions to form Hypothesis Space
• -Differentially express genes against Space

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Analysis Environment System

• Concepts and Genes are Universal Entities!
• Uniformly Represented
• Uniformly Manipulated
• Internally
• -Extract and Index Concepts within Collections
• -Navigate Concepts within Documents
• -Follow Genes from Documents into Databases

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Automatic Categorization v2

• Sorting of Spaces based on Metadata
• Sorting of Spaces based on Ontology
• MeSH for Medline Abstracts
• Gene Ontology computed for documents
• Sorting of Spaces based on Clustering
• Natural Maps from Small Worlds
• Steerable Maps from Language Models
• Semantic Indexing of Dynamic Spaces
• Fast System enables Interactive Sorting!

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Small World Graph
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Semantics Deeper and Faster

• Semantic Indexing across all of Medline
• Previous Attempts used Word Co-Occurrence
• Now Phrase Parser works general-purpose
• Now Mutual Information full differential
• Parallel Optimization of MI Graph
• Real-time Computation Shared Memory Cluster
• Interactive on our 16PC 256GB RAM workerbee
• Dynamic Spaces then Dynamic Semantic Indexing
• Interactive Clustering Natural Map
• Heuristic Approximation Small Worlds Graphs

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Dynamic Clustering

• Community Structure enables Dynamic Clustering
  with Large Vectors

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Automatic Curation v3

• Automatic Summarization of Genes
• Retrieve relevant sentences about gene
• Classify sentences into important aspects
• protein domain, homolog/ortholog
• expression pattern, phenotype function
• regulatory element, genetic interaction
• Generalizing to Biology Entities
• Genes, anatomical, behavior, chemical
• Question answering from biology factoids
• Computed Curation from Literature

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Gene Summary (FlyBase)
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Gene Summary (BeeSpace)

• Structured summary consists of relevant sentences
  covering 6 aspects of a gene
• Gene Products (GP)
• Expression Location (EL)
• Sequence Information (SI)
• Wild-type Function Phenotypic Information
  (WFPI)
• Mutant Phenotype (MP)
• Genetical Interaction (GI)

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Drosophila gene Abelson (Abl) tyrosine kinase
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Tribolium gene Scr
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Gene Summarizer New Aspects

• New categories (proposed by FlyBase curators)
• GP SI gt PS (protein domain or structure)
• SI gt HO (homologs or orthologs)
• EL gt EP (spatial/temporal expression patterns)
• SI gt RE (regulatory element information)
• WFPI MP gt PF (wild-type or mutant phenotype
  and function)
• GI gt IT (genetic or physical interaction)
• New (beyond FlyBase) gt PG (population genetics)
• Utilize cross-domain information for improving
  the GS on other organisms.

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BeeSpace System v3

• SPACES and REGIONS
• Dynamic and Relative
• Space is collection of documents
• Region is collection of terms
• Extract creates new Region from old Space
• Map creates new Space from old Region
• New from Old Spaces and Regions via merges
• Summarize classifies Gene within Space
• Annotate finds differential functional expression

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BeeSpace Semantic Operations

• Extract

• S

• R

• Map

• R

• S

• Merge (S1,S2) into S3
• Summarize (S) into Gene classify

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New Interface v4

• Single Window, Multiple Panes
• Space Panel, Service Tabs
• SPACES custom, system
• FILTER searching, sorting
• CLUSTER map natural and steerable
• SUMMARIZE categorize using space
• ANALYZE annotate using space

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Functional Analysis v4

• The software system goes beyond a searchable
  database, using statistical literature analyses
  to discover functional relationships between
  genes and behavior.
• This research will enable all scientists who
  study bee genes to live on the frontier of
  integrative biology, where biotechnology enables
  routine expression analysis and bioinformatics
  enables functional analysis
• unconstrained by pre-existing categories.
• Genelist Analyzer v4
• -Differential Expression of Gene Names against
  Space
• -Background is custom made Literature Space
• -Produces Concept List from Gene List
• -Analyze using Concept Navigation and Gene
  Summarization

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Question Answering v5

• Entities and Relations
• Question Answering templates
• Entity
• Gene, Anatomical
• Behavior, Chemical
• Relation
• Regulation (Gene-Gene)
• Expression (Gene-Anatomy)
• Function (Gene-Behavior) Biological Process
• Function (Gene-Chemical) Molecular Function

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Towards the Interspace

• The Analysis Environment technology is
  GENERAL! BirdSpace? BeeSpace?
• PigSpace? CowSpace?
• ArthropodSpace? AnimalSpace?
• BioSpace? MedSpace?