Computational Bioinformatics: Computational Bioinformatics: - PowerPoint PPT Presentation

Computational Bioinformatics: Computational Bioinformatics: Software and Databases Software and Databases Jason T. L. Wang, Professor Bioinformatics Program and Computer Science Department New Jersey Institute of Technology http://web.njit.edu/~wangj Work supported by NSF grant IIS-0707571 Presentation for NSF-Sponsored C2PRISM Program 7/31/2008 1

Outline • Introduction to Bioinformatics • Introduction to Computational RNA Genomics (Our Current Project) • RNA Informatics Tools • RNA Databases • Bioinformatics Center • Conclusion and Future Work 7/31/2008 2

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Gene: Gene: •Genetic information-containing elements •Genetic information-containing elements •Distributed to each cell when cell divides •Distributed to each cell when cell divides •Made of deoxyribonucleic acid --DNA •Made of deoxyribonucleic acid --DNA Gene Structure: •Promoter •Start codon •Introns •Exons •Stop codon •etc Gene: •Transcription : DNA to RNA • RNA Splicing: Remove Intons--mRNA •mRNA translation--Protein 7/31/2008 4

Gene Structure and Gene Expression CCCTGTGGAGCCACACCCTAGGGTTGGCCAATCTACTCCCAGGAGCAGG GAGGGCAGGAGCCAGGGCTGGGCATAAAAGTCAGGGCAGAGCCATCTAT TGCTTACATTTGCTTCTGACACAACTGTGTTCACTAGCAACTCAAACAG Exon 1 ACACCATGGTGCACCTGACTCCTGAGGAGAAGTCTGCCGTTACTGCCCT GTGGGCAAGGTGAACGTGGATGAAGTTGGTGGTGAGGCCCTGGGCAG GT TGGTATCAAGGTTACAAGACAGGTTTAAGGAGACCAATAGAAACTGGGC Acceptor site Acceptor site Start Codon Stop Codon Intron 1 ATGTGGAGACAGAGAAGACTCTTGGGTTTCTGATAGGCACTGACTCTCT Donor site Donor site Promoter CTGCCTATTGGTCTATTTTCCCACCCTT AG GCTGCTGGTGGTCTACCCT Intron 1 Intron 2 Exon 1 Exon 2 Exon 3 TGGACCCAGAGGTTCTTTGAGTCCTTTGGGGATCTGTCCACTCCTGATG Exon 2 CTGTATGGGCAACCCTAAGGTGAAGGCTCATGGCAAGAAAGTGCTCGGT GCCTTTAGTGATGGCCTGGCTCACCTGGACAACCTCAAGGGCACCTTTG Gene CCACACTGAGTGAGCTGCACTGTGACAAGCTGCACGTGGATCCTGAGAA CTTCAGG GT GAGTCTATGGGACCCTTGATGTTTTCTTTCCCCTTCTTTT CTATGGTTAAGTTCATGTCATAGGAAGGGGAGAAGTAACAGGGTACAGT Transcription TTAGAATGGGAAACAGACGAATGATTGCATCAGTGTGGAAGTCTCAGGA Acceptor site Acceptor site TCGTTTTAGTTTCTTTTATTGCTGTTCATAACAATTGTTTTCTTTTGTT Start Codon Stop Codon Donor site Donor site TAATTCTTGCTTTCTTTTTTTTTCTTCTCCGCAATTTTTACTATTATAC TTAATGCCTTAACATTGTGTATAACAAAAGGAAATATCTCTGAGATACA TTAAGTAACTTAAAAAAAAACTTTACACAGTCTGCCTAGTACATTACTA TTTGGAATATATGTGTGCTTATTTGCATATTCATAATCTCCCTACTTTA Intron 2 TTTTCTTTTATTTTTAATTGATACATAATCATTATACATATTTATGGGT pre-mRNA TAAAGTGTAATGTTTTAATATGTGTACACATATTGACCAAATCAGGGTA ATTTTGCATTTGTAAATTTTAAAAAATGCTTTCTTCTTTTAATATACTT TTTTGTTTATCTTATTTCTAATACTTTCCCTAATCTCTTTCTTTCAGGG Splicing( intron removal) CAATAATGATACAATGTATCATGCCTCTTTGCACCATTCTAAAGAATAA Start Codon Stop Codon CAGTGATAATTTCTGGGTTAAGGCAATAGCAATATTTCTGCATATAAAT ATTTCTGCATATAAATTGTAACTGATGTAAGAGGTTTCATATTGCTAAT AGCAGCTACAATCCAGCTACCATTCTGCTTTTATTTTATGGTTGGGATA AGGCTGGATTATTCTGAGTCCAAGCTAGGCCCTTTTGCTAATCATGTTC ATACCTCTATCTTCCTCCCAC AG CTCCTGGGCAACGTGCTGGTCTGTGT GCTGGCCCATCACTTTGGCAAAGAATTCACCCACCAGTGCAGGCTGCCT Exon 3 ATCAGAAAGTGGTGGCTGGTGTGGCTAATGCCCTGGCCCACAAGTATCA Splicing( RNA rejoining) CTAAGCTCGCTTTCTTGCTGTCCAATTTCTATTAAAGGTTCCTTTGTTC CCTAAGTCCAACTACTAAACTGGGGGATATTATGAAGGGCCTTGAGCAT Start Codon Stop Codon CTGGATTCTGCCTAATAAAAAACATTTATTTTCATTGCAATGATGTATT TAAATTATTTCTGAATATTTTACTAAAAAGGGAATGTGGGAGGTCAGTG CATTTAAAACATAAAGAAATGATGAGCTGTTCAAACCTTGGGAAAATAC ACTATATCTTAAACTCCATGAAAGAAGGTGAGGCTGCAACCAGCTAATG mRNA CACATTGGCAACAGCCCCTGATGCCTAATGCACATTGGCAACAGCCCCT GATGCCTATGCCTTATTCATCCCTCAGAAAAGGATTCTTGTAGAGGCTT GATTTGCAGGTTAAAGTTTTGCTATGCTGTATTTTACATTACTTATTGT TTTAGCTGTCCTCATGAATGTCTTTTC Translation Protein 7/31/2008 5

Computational RNA Genomics • Biochemical and genetic studies have demonstrated many functions associated with the UTRs in mRNAs. • Unlike proteins, RNA sequence search is insufficient for detecting similarity. 7/31/2008 6

Sequence Similarity vs. Structural Similarity >NM_000032 UUCGUUCGUCCUCAGUGCAGGGCAACAGGA ((((((.(((((......)))))))).))) >NM_014585 CAACUUCAGCUACAGUGUUAGCUAAGUUUG ((((((.(((((......)))))))).))) 7/31/2008 7

RSmatch and RADAR (BMC Bioinformatics 2005) (Nucleic Acids Research 2007) Alignment of two RNA secondary structures where the local matches found by RSmatch are in green. 7/31/2008 8

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Multiple Structural Alignment 7/31/2008 11

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GLEAN-UTR Database (BMC Genomics 2008) • Use RADAR, hierarchical clustering and Gene Ontology to mine RNA motifs in the UnTranslated Regions (UTRs) conserved between human and mouse orthologs in multiple genes sharing common biological pathways. • GLEAN-UTR DB contains 90 RNA motifs (structure groups) from 698 genes. Top two motifs are Iron response element (IRE) and histone 3’- UTR stem-loop structure. http://datalab.njit.edu/biodata/GLEAN-UTR-DB/ 7/31/2008 14

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Conclusion • We have developed a warehouse of informatics tools and databases for RNA genomics. • We want to invite high school students to our research team to conduct interesting research (Liberty Science Center Model) • Contact Dr. Jason Wang (wangj@njit.edu) • http://web.njit.edu/~wangj 7/31/2008 20

Computational Bioinformatics: Computational Bioinformatics: - PowerPoint PPT Presentation

Computational Bioinformatics: Computational Bioinformatics: Software and Databases Software and Databases Jason T. L. Wang, Professor Bioinformatics Program and Computer Science Department New Jersey Institute of Technology

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