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 MountBen Shneiderman

Harry Hochheiser is supported by a fellowship from America Online.

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Time Series Data• Real-Valued function over time• Goal: find patterns

– “Starts Low, Ends High”– Outliers– Periodic Patterns– Laggards and Leaders

• Hypothesis generation

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Microarray Data

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

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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

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TimeSearcher/Microrarray demo

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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

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Other Applications

• “Time”: linear ordered sequence• Use TimeSearcher for general sequences

– E.g., DNA

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SF1Splicing signals are recognized during earlysteps in the biochemical process of splicing.U2AF65

Exon 1U1

U2AF35

(Y)n AGExon 2

BranchSite

Application to the case of the Arabidopsis thaliana branch site consensus splicing signal.

Steve MountCell Biology and Molecular Genetics

Harry Hochheiser and Ben ShneidermanHuman Computer Interaction Lab

Steven SalzbergThe Institute for Genomic Research

TimeSearcher for analysis of weak signals in nucleotide sequences:

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Two-step pre-mRNA splicing mechanism with branched intermediate:

Diagram courtesy of Dr. Martinez Hewlett

Yeast (Saccharomyces cerevisiae)Invariant: TACTAAC

Humans (Homo sapiens)Consensus: TNYTRAYY

Fruit flies (Drosophila melanogaster)Invariant: WCTAATY

Weeds (Arabidopsis thaliana):Invariant: CTRAY

Consensus sequences:

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.’

Y = C or T; W = A or T; R = A or G; N = A, C, G or T

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ACTAA ACTGA ATAAC ATTGA CTAAA CTAAC CTAAT CTCAT CTGAC TAACG TAACT TCTAA TGACT TGATT TTAAC WYTRAY

Branch site

Pyrimidines

Distance to 3’ splice site

Num

ber

of

over-

repre

sente

d w

ord

s

one sigma

two sigma

Y = C or T; W = A or T; R = A or G; N = A, C, G or T

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.

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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?

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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