title: Comparative validation of the D. melanogaster modENCODE transcriptome annotation.
abstract: Accurate gene model annotation of reference genomes is critical for making them useful. The modENCODE project has improved the D. melanogaster genome annotation by using deep and diverse high-throughput data. Since transcriptional activity that has been evolutionarily conserved is likely to have an advantageous function, we have performed large-scale interspecific comparisons to increase confidence in predicted annotations. To support comparative genomics, we filled in divergence gaps in the Drosophila phylogeny by generating draft genomes for eight new species. For comparative transcriptome analysis, we generated mRNA expression profiles on 81 samples from multiple tissues and developmental stages of 15 Drosophila species, and we performed cap analysis of gene expression in D. melanogaster and D. pseudoobscura. We also describe conservation of four distinct core promoter structures composed of combinations of elements at three positions. Overall, each type of genomic feature shows a characteristic divergence rate relative to neutral models, highlighting the value of multispecies alignment in annotating a target genome that should prove useful in the annotation of other high priority genomes, especially human and other mammalian genomes that are rich in noncoding sequences. We report that the vast majority of elements in the annotation are evolutionarily conserved, indicating that the annotation will be an important springboard for functional genetic testing by the Drosophila community.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Zhen-Xia
authors.initials: ZX
authors.lastname: Chen
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: David
authors.initials: D
authors.lastname: Sturgill
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Jiaxin
authors.initials: J
authors.lastname: Qu
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Huaiyang
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authors.lastname: Jiang
authors.affiliation: Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
authors.forename: Soo
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authors.lastname: Park
authors.affiliation: Department of Statistics, University of California, Berkeley, California 94720, USA;
authors.forename: Nathan
authors.initials: N
authors.lastname: Boley
authors.affiliation: Technology Development Group, RIKEN Omics Science Center and RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama City, Kanagawa, Japan 230-0045;
authors.forename: Ana Maria
authors.initials: AM
authors.lastname: Suzuki
authors.affiliation: Division of Computational Bioscience, Center For Information Technology, National Institutes of Health, Bethesda, Maryland 20814, USA;
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Fletcher
authors.affiliation: Department of Evolution and Ecology, University of California, Davis, California 95616, USA;
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authors.initials: DC
authors.lastname: Plachetzki
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Peter C
authors.initials: PC
authors.lastname: FitzGerald
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Carlo G
authors.initials: CG
authors.lastname: Artieri
authors.affiliation: Department of Evolution and Ecology, University of California, Davis, California 95616, USA;
authors.forename: Joel
authors.initials: J
authors.lastname: Atallah
authors.affiliation: Department of Evolution and Ecology, University of California, Davis, California 95616, USA;
authors.forename: Olga
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authors.lastname: Barmina
authors.affiliation: Department of Statistics, University of California, Berkeley, California 94720, USA;
authors.forename: James B
authors.initials: JB
authors.lastname: Brown
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Kerstin P
authors.initials: KP
authors.lastname: Blankenburg
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Emily
authors.initials: E
authors.lastname: Clough
authors.affiliation: Clinical Trials and Outcomes Branch, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Abhijit
authors.initials: A
authors.lastname: Dasgupta
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Sai
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authors.lastname: Gubbala
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Yi
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authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Joy C
authors.initials: JC
authors.lastname: Jayaseelan
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Divya
authors.initials: D
authors.lastname: Kalra
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Yoo-Ah
authors.initials: YA
authors.lastname: Kim
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Christie L
authors.initials: CL
authors.lastname: Kovar
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Lee
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Mingmei
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authors.lastname: Li
authors.affiliation: Division of Computational Bioscience, Center For Information Technology, National Institutes of Health, Bethesda, Maryland 20814, USA;
authors.forename: James D
authors.initials: JD
authors.lastname: Malley
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: John H
authors.initials: JH
authors.lastname: Malone
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Tittu
authors.initials: T
authors.lastname: Mathew
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Nicolas R
authors.initials: NR
authors.lastname: Mattiuzzo
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Mala
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authors.lastname: Munidasa
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Donna M
authors.initials: DM
authors.lastname: Muzny
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Fiona
authors.initials: F
authors.lastname: Ongeri
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Lora
authors.initials: L
authors.lastname: Perales
authors.affiliation: National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Teresa M
authors.initials: TM
authors.lastname: Przytycka
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Ling-Ling
authors.initials: LL
authors.lastname: Pu
authors.affiliation: Department of Statistics, University of California, Berkeley, California 94720, USA;
authors.forename: Garrett
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authors.lastname: Robinson
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Rebecca L
authors.initials: RL
authors.lastname: Thornton
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
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authors.initials: N
authors.lastname: Saada
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Steven E
authors.initials: SE
authors.lastname: Scherer
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Harold E
authors.initials: HE
authors.lastname: Smith
authors.affiliation: National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Charles
authors.initials: C
authors.lastname: Vinson
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Crystal B
authors.initials: CB
authors.lastname: Warner
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Kim C
authors.initials: KC
authors.lastname: Worley
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Yuan-Qing
authors.initials: YQ
authors.lastname: Wu
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Xiaoyan
authors.initials: X
authors.lastname: Zou
authors.affiliation: Department of Biology, Indiana University, Bloomington, Indiana 47405, USA;
authors.forename: Peter
authors.initials: P
authors.lastname: Cherbas
authors.affiliation: Computer Science and Artificial Intelligence Laboratory, Massachusetts Institute of Technology, Cambridge, Massachusetts 20139, USA;
authors.forename: Manolis
authors.initials: M
authors.lastname: Kellis
authors.affiliation: Molecular and Cell Biology, University of California, Berkeley, California 94720, USA;
authors.forename: Michael B
authors.initials: MB
authors.lastname: Eisen
authors.affiliation: Department of Biology, New York University, New York, New York 10003, USA;
authors.forename: Fabio
authors.initials: F
authors.lastname: Piano
authors.affiliation: Department of Biology, New York University, New York, New York 10003, USA;
authors.forename: Karin
authors.initials: K
authors.lastname: Kionte
authors.affiliation: Department of Biology, New York University, New York, New York 10003, USA;
authors.forename: David H
authors.initials: DH
authors.lastname: Fitch
authors.affiliation: HHMI and Division of Biology, California Institute of Technology, Pasadena, California 91125, USA;
authors.forename: Paul W
authors.initials: PW
authors.lastname: Sternberg
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, M5S 3B2, Canada;
authors.forename: Asher D
authors.initials: AD
authors.lastname: Cutter
authors.affiliation: Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030-6403, USA.
authors.forename: Michael O
authors.initials: MO
authors.lastname: Duff
authors.affiliation: Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
authors.forename: Roger A
authors.initials: RA
authors.lastname: Hoskins
authors.affiliation: Department of Genetics and Developmental Biology, Institute for Systems Genomics, University of Connecticut Health Center, Farmington, Connecticut 06030-6403, USA.
authors.forename: Brenton R
authors.initials: BR
authors.lastname: Graveley
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Richard A
authors.initials: RA
authors.lastname: Gibbs
authors.affiliation: Department of Statistics, University of California, Berkeley, California 94720, USA;
authors.forename: Peter J
authors.initials: PJ
authors.lastname: Bickel
authors.affiliation: Department of Evolution and Ecology, University of California, Davis, California 95616, USA;
authors.forename: Artyom
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authors.lastname: Kopp
authors.affiliation: Technology Development Group, RIKEN Omics Science Center and RIKEN Center for Life Science Technologies, Division of Genomic Technologies, Yokohama City, Kanagawa, Japan 230-0045;
authors.forename: Piero
authors.initials: P
authors.lastname: Carninci
authors.affiliation: Department of Genome Dynamics, Life Sciences Division, Lawrence Berkeley National Laboratory, Berkeley, California 94720, USA;
authors.forename: Susan E
authors.initials: SE
authors.lastname: Celniker
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892, USA;
authors.forename: Brian
authors.initials: B
authors.lastname: Oliver
authors.affiliation: Human Genome Sequencing Center, Baylor College of Medicine, Houston, Texas 77030, USA;
authors.forename: Stephen
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authors.lastname: Richards
mesh_terms: D000818:Animals; D016000:Cluster Analysis; D019295:Computational Biology / Q000379:methods*; D004331:Drosophila melanogaster / Q000145:classification / Q000235:genetics*; D019143:Evolution, Molecular; D005091:Exons; D005260:Female; D020869:Gene Expression Profiling; D049750:Genome, Insect; D006801:Humans; D008297:Male; D058977:Molecular Sequence Annotation; D059372:Nucleotide Motifs; D010802:Phylogeny; D056510:Position-Specific Scoring Matrices; D011401:Promoter Regions, Genetic; D017393:RNA Editing; D022821:RNA Splice Sites; D012326:RNA Splicing; D015203:Reproducibility of Results; D024363:Transcription Initiation Site; D059467:Transcriptome
chemical_list: D022821:RNA Splice Sites