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TimeSearcher: Interactive Querying for Identification of Patterns in Genetic Data

TimeSearcher: Interactive Querying for Identification of Patterns in Genetic Data. Harry Hochheiser Eric Baehrecke Stephen Mount Ben Shneiderman. Harry Hochheiser is supported by a fellowship from America Online. Time Series Data. Real-Valued function over time Goal: find patterns

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TimeSearcher: Interactive Querying for Identification of Patterns in Genetic Data

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  1. TimeSearcher: Interactive Querying for Identification of Patterns in Genetic Data Harry Hochheiser Eric Baehrecke Stephen Mount Ben Shneiderman Harry Hochheiser is supported by a fellowship from America Online.

  2. Time Series Data • Real-Valued function over time • Goal: find patterns • “Starts Low, Ends High” • Outliers • Periodic Patterns • Laggards and Leaders • Hypothesis generation

  3. Microarray Data Chu, et al. The transcriptional program of sporulation in budding yeast, Science 1998 Oct 23; 282(5389): 699-705.

  4. Timeboxes • Rectangular query regions • Value must be in range for all time points in region • Combine multiple timeboxes for conjunctive query Sharp Rise Panic Reversal

  5. TimeSearcher/Microrarray demo

  6. TimeSearcher • Interactive exploration of time-series data • Dynamic queries (<100ms) • Linear display of individual items • Create queries on graph area • Move, scale timeboxes to modify query • Drag-and-Drop for query-by-example

  7. Other Applications • “Time”: linear ordered sequence • Use TimeSearcher for general sequences • E.g., DNA

  8. TimeSearcher for analysis of weak signals in nucleotide sequences: Application to the case of the Arabidopsis thaliana branch site consensus splicing signal. Steve Mount Cell Biology and Molecular Genetics Harry Hochheiser and Ben Shneiderman Human Computer Interaction Lab Steven Salzberg The Institute for Genomic Research U1 Exon 1 SF1 Splicing signals are recognized during early steps in the biochemical process of splicing. U2AF65 Branch Site U2AF35 Exon 2 (Y)n AG

  9. Consensus sequences: Two-step pre-mRNA splicing mechanism with branched intermediate: Yeast (Saccharomyces cerevisiae) Invariant: TACTAAC Humans (Homo sapiens) Consensus: TNYTRAYY Fruit flies (Drosophila melanogaster) Invariant: WCTAATY Weeds (Arabidopsis thaliana): Invariant: CTRAY Diagram courtesy of Dr. Martinez Hewlett Y = C or T; W = A or T; R = A or G; N = A, C, G or T Here we sought to verify and extend the experimentally determined branch site consensus CTRAY determined by Simpson et al. (2002). Our long-term goal is the characterization of an even weaker signal, the ‘exonic splicing enhancer.’

  10. Conclusions: TimeSearcher can be used to identify weak signals in aligned nucleotide sequences. Analysis of 8,550 exons from Arabidopsis supports the branch site consensus WYTRAY. ACTAA ACTGA ATAAC ATTGA CTAAA CTAAC CTAAT CTCAT CTGAC TAACG TAACT TCTAA TGACT TGATT TTAAC WYTRAY one sigma Branch site Number of over-represented words two sigma Pyrimidines Y = C or T; W = A or T; R = A or G; N = A, C, G or T Distance to 3’ splice site

  11. Future Work: Extensions to query model • Leaders and Laggards • Identification of regulatory genes • Multiple time-varying values • Variable Time timeboxes • Collaborations with biologists inform design What sort of queries are of interest?

  12. Conclusions • TimeSearcher: interactive tool for graphical exploration of time series data • Ongoing use for analyzing microarray data and sequence data We’re interested in working with motivated users & real data sets www.cs.umd.edu/hcil/timesearcher

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