The baboon kidney transcriptome: analysis of transcript sequence, splice variants, and abundance

Abstract

The baboon is an invaluable model for the study of human health and disease, including many complex diseases of the kidney. Although scientists have made great progress in developing this animal as a model for numerous areas of biomedical research, genomic resources for the baboon, such as a quality annotated genome, are still lacking. To this end, we characterized the baboon kidney transcriptome using high-throughput cDNA sequencing (RNA-Seq) to identify genes, gene variants, single nucleotide polymorphisms (SNPs), insertion-deletion polymorphisms (InDels), cellular functions, and key pathways in the baboon kidney to provide a genomic resource for the baboon. Analysis of our sequencing data revealed 45,499 high-confidence SNPs and 29,813 InDels comparing baboon cDNA sequences with the human hg18 reference assembly and identified 35,900 cDNAs in the baboon kidney, including 35,150 transcripts representing 15,369 genic genes that are novel for the baboon. Gene ontology analysis of our sequencing dataset also identified numerous biological functions and canonical pathways that were significant in the baboon kidney, including a large number of metabolic pathways that support known functions of the kidney. The results presented in this study catalogues the transcribed mRNAs, noncoding RNAs, and hypothetical proteins in the baboon kidney and establishes a genomic resource for scientists using the baboon as an experimental model.

Figure 1. Graphical representation of oxidative phosphorylation and mitochondrial dysfunction pathways revealed significant genes in baboon kidney.

IPA was used to identify canonical pathways from the IPA library that were most significant in the baboon kidney RNA-Seq dataset. Molecules from the dataset that met a fold coverage cutoff of 302.8 and were associated with a canonical pathway in Ingenuity's knowledge Base were considered for the analysis. Oxidative phosphorylation and mitochondrial dysfunction were identified as the two most significant pathways in the dataset. Groups of molecules in the oxidative phosphorylation and mitochondrial dysfunction pathways are represented as various shades of red. The intensity of the node color indicates the degree of fold coverage in the RNA-Seq dataset. Nodes shown in gray represent genes from the dataset that did not meet the fold coverage cutoff, and nodes shown in white represent genes that are in IPA's Knowledge Base but not in the dataset. Members within each significant group of molecules are shown in Table S20.

Figure 2. Network of genes associated with cancer, cell death, cellular assembly and organization in baboon kidney.

Each transcript and corresponding fold coverage value was imported into IPA and mapped to its corresponding gene in the IPA Knowledge Base. A fold coverage value of 302.8 was set to limit the number of molecules considered for the analysis. Genes meeting the cutoff criteria were overlaid onto a global molecular network developed from information within the IPA Knowledge Base, and the networks were then algorithmically generated based on their connectivity. Graphical representation of the network reveals genes with highest fold coverage in the baboon kidney. Genes are represented as nodes of various shapes to represent the functional class of the gene product, and the biological relationship between two nodes is represented as a line. The intensity of the node color indicates the degree of fold coverage.