Accurate Identification of Novel Human Genes Through Simultaneous Gene Prediction in Human, Mouse, and Rat

Dewey, Colin N.; Wu, Jia Qian; Cawley, S.; Alexandersson, Marina; Gibbs, Richard A.; Pachter, Lior

doi:10.1101/gr.1939804

Cited by 28 publications

(11 citation statements)

References 19 publications

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“…In general, the states of the model now contain probability distributions for an alignment of two residues, and by using several different states, a pHMM can be used to model different patterns of conservation. For example, pHMM systems to identify protein-coding genes [36,37] include different states corresponding to pairs of aligned coding and noncoding nucleotides as well as splice sites. The standard HMM algorithms have been generalized and described in more detail for pHMMs [22,37] or, more generally, phylogenetic HMMs [30,38].…”

Section: Methodsmentioning

confidence: 99%

Recognition of Unknown Conserved Alternatively Spliced Exons

2005

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The split structure of most mammalian protein-coding genes allows for the potential to produce multiple different mRNA and protein isoforms from a single gene locus through the process of alternative splicing (AS). We propose a computational approach called UNCOVER based on a pair hidden Markov model to discover conserved coding exonic sequences subject to AS that have so far gone undetected. Applying UNCOVER to orthologous introns of known human and mouse genes predicts skipped exons or retained introns present in both species, while discriminating them from conserved noncoding sequences. The accuracy of the model is evaluated on a curated set of genes with known conserved AS events. The prediction of skipped exons in the ~1% of the human genome represented by the ENCODE regions leads to more than 50 new exon candidates. Five novel predicted AS exons were validated by RT-PCR and sequencing analysis of 15 introns with strong UNCOVER predictions and lacking EST evidence. These results imply that a considerable number of conserved exonic sequences and associated isoforms are still completely missing from the current annotation of known genes. UNCOVER also identifies a small number of candidates for conserved intron retention.

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Section: Methodsmentioning

confidence: 99%

Recognition of Unknown Conserved Alternatively Spliced Exons

2005

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“…); on the other hand, de novo approaches, while less accurate, can reliably identify genes with no transcriptional evidence beforehand. The simultaneous use of two or more genomes by de novo gene predictors (called comparative gene predictors) has proven extremely effective, not only in improving sensitivity over single-genome methods but also in finding novel genes (5–7), where novel specifies genes that fall outside a core set of annotated gene loci for a given genome. Here, we use SGP2 as a comparative gene predictor (8).…”

Section: Introductionmentioning

confidence: 99%

Comparative gene finding in chicken indicates that we are closing in on the set of multi-exonic widely expressed human genes

Castelo¹

2005

Nucleic Acids Research

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The recent availability of the chicken genome sequence poses the question of whether there are human protein-coding genes conserved in chicken that are currently not included in the human gene catalog. Here, we show, using comparative gene finding followed by experimental verification of exon pairs by RT–PCR, that the addition to the multi-exonic subset of this catalog could be as little as 0.2%, suggesting that we may be closing in on the human gene set. Our protocol, however, has two shortcomings: (i) the bioinformatic screening of the predicted genes, applied to filter out false positives, cannot handle intronless genes; and (ii) the experimental verification could fail to identify expression at a specific developmental time. This highlights the importance of developing methods that could provide a reliable estimate of the number of these two types of genes.

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“…Here we employed a comparative genomics approach on a large number of organisms. Comparative genomics approaches have been proven to be very powerful in gene finding (Dewey et al, 2004;Taher SMALL RNAS IN BACTERIAL GENOMES 69 FIG. 7.…”

Section: Discussionmentioning

confidence: 99%

Comparative Genomics of Small RNAs in Bacterial Genomes

Luban¹

2007

OMICS: A Journal of Integrative Biology

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In recent years, various families of small non-coding RNAs (sRNAs) have been discovered by experimental and computational approaches, both in bacterial and eukaryotic genomes. Although most of them await elucidation of their function, it has been reported that some play important roles in gene regulation. Here we carried out comparative genomics analysis of possible sRNAs that are computationally identified in 30 bacterial genomes from gamma- and alpha-proteobacteria and Deinococcus radiodurans. Identified sRNAs are clustered by a complete-linkage clustering method to see conservation among the organisms. On average, sRNAs are found in approximately 30% of intergenic regions of each genome sequence. Of these, 25.7% are conserved among three or more organisms. Approximately 60% of the conserved sRNAs do not locate in orthologous intergenic regions, implying that sRNAs may be shuffled their positions in genomes. The current study implies that sRNAs may be involved in a more extensive range of functions in bacteria.

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Accurate Identification of Novel Human Genes Through Simultaneous Gene Prediction in Human, Mouse, and Rat

Cited by 28 publications

References 19 publications

Recognition of Unknown Conserved Alternatively Spliced Exons

Recognition of Unknown Conserved Alternatively Spliced Exons

Comparative gene finding in chicken indicates that we are closing in on the set of multi-exonic widely expressed human genes

Comparative Genomics of Small RNAs in Bacterial Genomes

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