Published on June 29, 2009
"Junk" DNA Proves to be Highly Valuable1
What 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.2
Cooper 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 genome genes Functional 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 genes Rigoutsos, Isidore et al. (2006) Proc. Natl. Acad. Sci. USA 103, 6605-6610 Copyright ©2006 by the National Academy of Sciences
WordSeekerA Software Suite for Discovery and Characterization of Genomic Words and Genome-Wide Patterns
word discovery methods sequence-driven (alignment-based) pattern-driven (enumerative) exhaustive optimized probabilistic optimization deterministic optimization YMF preprocess combine short patterns AlignAce MEME WINNOWER heuristic exact Teiresias, WordSeeker suffix tree, Weeder GuhaThakurta 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 Genomics sequence(s) words WORDIFIER scientist scientist
OWEF: An Open Source Word Enumeration Framework for Bioinformatics Kyle Kurz, Lonnie R. Welch, Frank Drews, Lee Nau, Jens Lichtenberg Ohio University School of EECS Bioinformatics Laboratory
Motivation Create a robust Motif Discovery framework using abstracted core algorithms Use a modular design, allowing new methods and algorithms to be implemented quickly and easily Abstract C++ classes Easily extensible Support the Scientific Discovery process
Project Information Project: http://bio-s1.cs.ohiou.edu/~wordseek/download/ Open Source License: GNU General Public License (GPL v3) Language: C++ Applications: Currently in final testing phase Future Work: Will provide backend for WordSeeker tool at Ohio University and Ohio Supercomputer Center Will be used to fully analyze the Arabidopsis thaliana genome
Open Source Implementation of Batch Extraction for Coding and Non-Coding Sequences Jens Lichtenberg, Lonnie R. Welch Bioinformatics Laboratory School of EECS Ohio University
Motivation Regulatory 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 organism Ensembl API provides limited functionality
Approach connect to Ensembl database Input Output Set up repository Retrieve Gene Adaptor create gene object Gene Symbol Retrieve 5’UTR Retrieve 3’UTR Retrieve Exons Retrieve Upstream Adaptor Retrieve Introns Retrieve Promoter Promoter length Output Files
Project Information Project: http://opensource.msseeker.org GNU General Public License (GPL) Language: Perl Integrated in WordSeeker motif discovery tool of Ohio University Bioinformatics Lab Future Work: Connection to Genbank repository information Release into BioPerl or CPAN
Acknowledgements Thomas Bitterman, OSC Laura Elnitski, NHGRI Susan Evans, OU Matt Geisler, SIU Erich Grotewold , OSU Edwin Jacox, NHGRI Stephen S. Lee, U. Idaho Pooja M. Majmudar, OU Paul Morris, BGSU Chase Nelson, Oberlin Eric Stockinger , OSU Sarah Wyatt, OU Alper Yilmaz, OSU Jeffrey Parvin, OSU Kun Huang, OSU Thomas Mitchell , OSU Kengo Morohashi, OSU Rebecca Lamb , OSU John Finer, OSU Lonnie WelchJens LichtenbergRami AlouranFrank DrewsKyle KurzXiaoyu LiangLee NauMatt WileyRazvan BunescuJoshua D. Welch Klaus EckerMohit AlamNathaniel GeorgeDazhang GuEric PetriJosiah SeamanKaiyu ShenCollaborators WordSeeker Team Former Members of the team
Joshua D. Welch
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 .” 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 manifestedSolution 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 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, Headline With the availability of the genomic sequences of numerous organisms, life scientists are working in conjunction with bioinformaticians to decipher the meanings of the genomes. Projects such as Encyclopedia of Genomic Elements (ENCODE)  and Pyknons , 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
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