We propose to generate comprehensive nonhuman primate (NHP) reference transcriptome databases using lllumina's next-generation sequencing platform. These databases will contain information on protein-coding, long noncoding, and small noncoding transcripts, and will provide vast amounts of new information regarding gene and transcript structure, expression, and regulation. To enhance this resource, we will also generate a tissue-specific transcriptome atlas for rhesus macaque and whole transcriptome information from a NHP model of AIDS. These databases will serve as a resource for scientists working on evolution, comparative biology, genetics, genomics, and NHP models of human disease.
In Aim 1, we will collaborate with lllumina scientists to generate whole transcriptome (protein-coding and long noncoding) information for 14 NHP species/subspecies, lllumina will perform this sequencing at no cost to the application. The majority of these NHP genomes will be sequenced within the year, and transcriptome information will facilitate genome assembly, annotation, development of new tools for systems biology research, while also providing broad resources for evolutionary biologists. To complement the whole transcriptome project, we will use our lllumina Genome Analyzer to generate a tissue specific transcriptome for rhesus macaque, the most widely used NHP in biomedical research.
In Aim 2, we will sequence protein-coding, long noncoding, and small noncoding transcripts from an independently funded study focused on a NHP acute infection model of AIDS. The resulting data will expand the NHP reference transcriptome databases to include new information on virus-host interactions, innate immunity, inflammatory processes, the transition to the adaptive immune response, and infection-induced transcripts. Finally, whole transcriptome data from both Aims will enable the discovery and quantification of noncoding RNAs, which have widespread functionality but are not well understood. Given the importance of NHP primates as models for human health and disease, it is imperative that whole transcriptome information be available for these animals.
We will use new sequencing technologies to generate information about the structure of nonhuman primate genomes;and the vast diversity of transcripts that these genomes express. This information will have a wide variety of uses, including helping to understand the role of these transcripts in human diseases such as AIDS, the identification of new drug targets, or the design of new vaccine strategies.
|Barrenas, Fredrik; Palermo, Robert E; Agricola, Brian et al. (2014) Deep transcriptional sequencing of mucosal challenge compartment from rhesus macaques acutely infected with simian immunodeficiency virus implicates loss of cell adhesion preceding immune activation. J Virol 88:7962-72|
|Li, Sheng; Tighe, Scott W; Nicolet, Charles M et al. (2014) Multi-platform assessment of transcriptome profiling using RNA-seq in the ABRF next-generation sequencing study. Nat Biotechnol 32:915-25|
|Falzarano, Darryl; de Wit, Emmie; Feldmann, Friederike et al. (2014) Infection with MERS-CoV causes lethal pneumonia in the common marmoset. PLoS Pathog 10:e1004250|
|Peng, Xinxia; Sova, Pavel; Green, Richard R et al. (2014) Deep sequencing of HIV-infected cells: insights into nascent transcription and host-directed therapy. J Virol 88:8768-82|
|Couger, M Brian; Pipes, Lenore; Squina, Fabio et al. (2014) Enabling large-scale next-generation sequence assembly with Blacklight. Concurr Comput 26:2157-2166|
|Peng, Xinxia; Pipes, Lenore; Xiong, Hao et al. (2014) Assessment and improvement of Indian-origin rhesus macaque and Mauritian-origin cynomolgus macaque genome annotations using deep transcriptome sequencing data. J Med Primatol 43:317-28|
|Selinger, Christian; Katze, Michael G (2013) Mathematical models of viral latency. Curr Opin Virol 3:402-7|