"Junk" DNA Proves to be Highly Valuable1What was once thought of as DNA with zero value in plants--dubbed "junk" DNA--may turn out to be key in helping scientists improve the control of gene expression in transgenic crops.2Cooper and collaborators investigated "junk" DNA in the model plant Arabidopsis thaliana, using a computer program to find short segments of DNA that appeared as molecular patterns…These linked patterns are called pyknons…This discovery in plants illustrates that the link between coding DNA and junk DNA crosses higher orders of biology and suggests a universal genetic mechanism at play that is not yet fully understood. 1-Alfredo Flores, June 2, 2009; http://www.ars.usda.gov/is/pr/2009/090602.htm.2-Bret Cooper, Soybean Genomics and Improvement Laboratory, Agricultural Research Service, USDA.

“Perhaps it is time tobid farewell to the term ‘junk’ DNA – we knew not your true nature.” (Regulatory RNAs and the demise of ‘junk’ DNA. Genome Biology 2006, 7:328)The genomegenesFunctional elements?Functional Elements: 90%?? Junk: 10%??"...a certain amount of hubris was required for anyone to call any part of the genome 'junk,' given our level of ignorance."(Francis Collins, 2006)

Fig. 1. Pyknons in the 3' UTRs of the apoptosis inhibitor birc4 (shown above the horizontal line) and nine other genesRigoutsos, Isidore et al. (2006) Proc. Natl. Acad. Sci. USA 103, 6605-6610Copyright ©2006 by the National Academy of Sciences

WordSeekerA Software Suite for Discovery and Characterization of Genomic Words and Genome-Wide Patterns

www.word-seeker.org

word discovery methodssequence-driven(alignment-based)pattern-driven(enumerative)exhaustiveoptimizedprobabilisticoptimizationdeterministicoptimizationYMFpreprocesscombine short patternsAlignAceMEMEWINNOWERheuristicexactTeiresias,WordSeekersuffix tree,WeederGuhaThakurta D., Computational identification of transcriptional regulatory elements in DNA sequence. Nucleic Acids Res. 2006 Jul 19;34(12):3585-98. Print 2006. Review. Sandve GK, Drabløs F., A survey of motif discovery methods in an integrated framework. Biol Direct. 2006 Apr 6;1:11.

The WORDIFIER Pattern for Functional and Regulatory Genomicssequence(s)wordsWORDIFIERscientistscientist

OWEF: An Open Source Word Enumeration Framework for BioinformaticsKyle Kurz, Lonnie R. Welch, Frank Drews, Lee Nau, Jens LichtenbergOhio University School of EECS Bioinformatics Laboratory

MotivationCreate a robust Motif Discovery framework using abstracted core algorithmsUse a modular design, allowing new methods and algorithms to be implemented quickly and easilyAbstract C++ classesEasily extensibleSupport the Scientific Discovery process

Approach

Project InformationProject: http://bio-s1.cs.ohiou.edu/~wordseek/download/Open Source License: GNU General Public License (GPL v3)Language: C++Applications:Currently in final testing phaseFuture Work:Will provide backend for WordSeeker tool at Ohio University and Ohio Supercomputer CenterWill be used to fully analyze the Arabidopsis thaliana genome

Open Source Implementation of Batch Extraction for Coding and Non-Coding SequencesJens Lichtenberg, Lonnie R. WelchBioinformatics LaboratorySchool of EECSOhio University

MotivationRegulatory Genomics tools return and operate on lists of Gene Symbols (e.g. STAT5A, Cd59a, Slc35f4)To our knowledge, no currently supported, open source “tool” that allows extraction of specific non-coding sequences for any organismEnsembl API provides limited functionality

Approachconnect to Ensembl databaseInputOutputSet up repositoryRetrieve Gene Adaptorcreate gene objectGene SymbolRetrieve 5’UTRRetrieve 3’UTRRetrieve ExonsRetrieve Upstream AdaptorRetrieve IntronsRetrieve PromoterPromoter lengthOutput Files

Project InformationProject: http://opensource.msseeker.orgGNU General Public License (GPL)Language: PerlIntegrated in WordSeeker motif discovery tool of Ohio University Bioinformatics LabFuture Work:Connection to Genbank repository informationRelease into BioPerl or CPAN

AcknowledgementsThomas Bitterman, OSCLaura Elnitski, NHGRISusan Evans, OUMatt Geisler, SIUErich Grotewold , OSUEdwin Jacox, NHGRIStephen S. Lee, U. IdahoPooja M. Majmudar, OUPaul Morris, BGSUChase Nelson, OberlinEric Stockinger , OSUSarah Wyatt, OUAlper Yilmaz, OSUJeffrey Parvin, OSUKun Huang, OSUThomas Mitchell , OSUKengo Morohashi, OSURebecca Lamb , OSUJohn Finer, OSULonnie WelchJens LichtenbergRami AlouranFrank DrewsKyle KurzXiaoyu LiangLee NauMatt WileyRazvan BunescuJoshua D. Welch Klaus EckerMohit AlamNathaniel GeorgeDazhang GuEric PetriJosiah SeamanKaiyu ShenCollaboratorsWordSeeker TeamFormer Members of the team

Lonnie Welch

Jens Lichtenberg

Rami Alouran

Frank Drews

Kyle Kurz

Xiaoyu Liang

Lee Nau

Matt Wiley

Razvan Bunescu

Joshua D. Welch

Klaus Ecker

Mohit Alam

Nathaniel George

Dazhang Gu

Eric Petri

Josiah Seaman

Kaiyu Shen

a pattern “describes a problem which occurs over and over again in our environment, and then describes the core of the solution to that problem, in such a way that you can use the solution a million times over, without ever doing it the same way twice [1].” C. Alexander, S. Ishikawa, and M. Silverstein, A Pattern Language: Towns, Buildings, Construction. Oxford University Press, 1977.

Alexander Pattern Format Picture – a representative example Introductory paragraph - sets the contextHeadline - the essence of the problem in one or two sentences. Body – empirical background of the pattern evidence for its validity range of different ways the pattern can be manifestedSolutionrelationships which are required to solve the stated problem in the stated context. stated in the form of an instruction—so that you know exactly what you need to do, to build the patternDiagram - shows the solution, with labels to indicate its main componentsA paragraph which ties the pattern to all those smaller patterns in the language, which are needed to complete this pattern, to embellish it, to fill it out…

empirical background of the pattern

evidence for its validity

range of different ways the pattern can be manifested

relationships which are required to solve the stated problem in the stated context.

stated in the form of an instruction—so that you know exactly what you need to do, to build the pattern

Picture, Introduction, HeadlineWith the availability of the genomic sequences ofnumerous organisms, life scientists are working in conjunction with bioinformaticians to decipher the meanings of the genomes. Projects such as Encyclopedia of Genomic Elements (ENCODE) [2] and Pyknons [3], seek to identify and charatcetrize the functional elements in genomes. The functional elements are often referred to as words.Given a genomic sequence (or a set of sequences), an important problem is the enumeration of all subsequences (words) contained in the sequence (or the set of sequences).The WORDIFIER Pattern for Functional and Regulatory Genomics