RESUMO
BACKGROUND: The genome annotations of rhesus (Macaca mulatta) and cynomolgus (Macaca fascicularis) macaques, two of the most common non-human primate animal models, are limited. METHODS: We analyzed large-scale macaque RNA-based next-generation sequencing (RNAseq) data to identify un-annotated macaque transcripts. RESULTS: For both macaque species, we uncovered thousands of novel isoforms for annotated genes and thousands of un-annotated intergenic transcripts enriched with non-coding RNAs. We also identified thousands of transcript sequences which are partially or completely 'missing' from current macaque genome assemblies. We showed that many newly identified transcripts were differentially expressed during SIV infection of rhesus macaques or during Ebola virus infection of cynomolgus macaques. CONCLUSIONS: For two important macaque species, we uncovered thousands of novel isoforms and un-annotated intergenic transcripts including coding and non-coding RNAs, polyadenylated and non-polyadenylated transcripts. This resource will greatly improve future macaque studies, as demonstrated by their applications in infectious disease studies.
Assuntos
Doença pelo Vírus Ebola/genética , Macaca fascicularis , Macaca mulatta , Doenças dos Macacos/genética , Síndrome de Imunodeficiência Adquirida dos Símios/genética , Transcriptoma , Animais , Ebolavirus/fisiologia , Doença pelo Vírus Ebola/virologia , Sequenciamento de Nucleotídeos em Larga Escala , Índia , Maurício , Dados de Sequência Molecular , Doenças dos Macacos/virologia , RNA não Traduzido/genética , RNA não Traduzido/metabolismo , Análise de Sequência de RNA , Síndrome de Imunodeficiência Adquirida dos Símios/virologia , Vírus da Imunodeficiência Símia/fisiologiaRESUMO
MOTIVATION: The sequencing of the Plasmodium yoelii genome, a model rodent malaria parasite, has greatly facilitated research for the development of new drug and vaccine candidates against malaria. Unfortunately, only preliminary gene models were annotated on the partially sequenced genome, mostly by in silico gene prediction, and there has been no major improvement of the annotation since 2002. RESULTS: Here we report on a systematic assessment of the accuracy of the genome annotation based on a detailed analysis of a comprehensive set of cDNA sequences and proteomics data. We found that the coverage of the current annotation tends to be biased toward genes expressed in the blood stages of the parasite life cycle. Based on our proteomic analysis, we estimate that about 15% of the liver stage proteome data we have generated is absent from the current annotation. Through comparative analysis we identified and manually curated a further 510 P. yoelii genes which have clear orthologs in the P. falciparum genome, but were not present or incorrectly annotated in the current annotation. This study suggests that improvements of the current P. yoelii genome annotation should focus on genes expressed in stages other than blood stages. Comparative analysis will be critically helpful for this re-annotation. The addition of newly annotated genes will facilitate the use of P. yoelii as a model system for studying human malaria. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.