title: Prediction and characterization of noncoding RNAs in C. elegans by integrating conservation, secondary structure, and high-throughput sequencing and array data.
abstract: We present an integrative machine learning method, incRNA, for whole-genome identification of noncoding RNAs (ncRNAs). It combines a large amount of expression data, RNA secondary-structure stability, and evolutionary conservation at the protein and nucleic-acid level. Using the incRNA model and data from the modENCODE consortium, we are able to separate known C. elegans ncRNAs from coding sequences and other genomic elements with a high level of accuracy (97% AUC on an independent validation set), and find more than 7000 novel ncRNA candidates, among which more than 1000 are located in the intergenic regions of C. elegans genome. Based on the validation set, we estimate that 91% of the approximately 7000 novel ncRNA candidates are true positives. We then analyze 15 novel ncRNA candidates by RT-PCR, detecting the expression for 14. In addition, we characterize the properties of all the novel ncRNA candidates and find that they have distinct expression patterns across developmental stages and tend to use novel RNA structural families. We also find that they are often targeted by specific transcription factors (∼59% of intergenic novel ncRNA candidates). Overall, our study identifies many new potential ncRNAs in C. elegans and provides a method that can be adapted to other organisms.
authors.affiliation: Program in Computational Biology and Bioinformatics, Yale University, New Haven, Connecticut 06520, USA.
authors.forename: Zhi John
authors.initials: ZJ
authors.lastname: Lu
authors.forename: Kevin Y
authors.initials: KY
authors.lastname: Yip
authors.forename: Guilin
authors.initials: G
authors.lastname: Wang
authors.forename: Chong
authors.initials: C
authors.lastname: Shou
authors.forename: Ladeana W
authors.initials: LW
authors.lastname: Hillier
authors.forename: Ekta
authors.initials: E
authors.lastname: Khurana
authors.forename: Ashish
authors.initials: A
authors.lastname: Agarwal
authors.forename: Raymond
authors.initials: R
authors.lastname: Auerbach
authors.forename: Joel
authors.initials: J
authors.lastname: Rozowsky
authors.forename: Chao
authors.initials: C
authors.lastname: Cheng
authors.forename: Masaomi
authors.initials: M
authors.lastname: Kato
authors.forename: David M
authors.initials: DM
authors.lastname: Miller
authors.forename: Frank
authors.initials: F
authors.lastname: Slack
authors.forename: Michael
authors.initials: M
authors.lastname: Snyder
authors.forename: Robert H
authors.initials: RH
authors.lastname: Waterston
authors.forename: Valerie
authors.initials: V
authors.lastname: Reinke
authors.forename: Mark B
authors.initials: MB
authors.lastname: Gerstein
mesh_terms: D000465:Algorithms; D000818:Animals; D001665:Binding Sites / Q000235:genetics; D017173:Caenorhabditis elegans / Q000235:genetics*; D021901:DNA, Intergenic / Q000235:genetics; D020869:Gene Expression Profiling; D059014:High-Throughput Nucleotide Sequencing; D058977:Molecular Sequence Annotation; D009690:Nucleic Acid Conformation; D020411:Oligonucleotide Array Sequence Analysis; D012319:RNA Polymerase II / Q000378:metabolism; D022661:RNA, Untranslated / Q000737:chemistry* / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism
chemical_list: D021901:DNA, Intergenic; D022661:RNA, Untranslated; D014157:Transcription Factors; D012319:RNA Polymerase II