Dataset Information

Cross-species gene expression analysis of species-specific differences in preclinical assessment of pharmaceutical compounds (rat)

ABSTRACT: Significant qualitative and quantitative differences exist between humans and the animal models used in research. However, significant quantitative and qualitative differences exist between humans and the animal models used in research. This is as a result of genetic variation between human and the laboratory animal. Therefore the development of a system that would allow the assessment of all molecular differences between species after drug exposure would have a significant impact on drug evaluation for toxicity and efficacy. Here we describe a cross-species microarray methodology that identifies and selects orthologous probes after cross-species sequence comparison to develop an orthologous cross-species gene expression analysis tool. The assumptions made by the use of this orthologous gene expression strategy for cross-species extrapolation is that; conserved changes in gene expression equate to conserved pharmacodynamic endpoints. This assumption is supported by the fact that evolution and selection have maintained the structure and function of many biochemical pathways over time, resulting in the conservation of many important processes. We demonstrate this difference using a cross-species methodology by investigating species specific differences of the peroxisome proliferator activator receptor (PPAR) alpha in rat and human.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE47695 | GEO | 2014/04/30

SECONDARY ACCESSION(S): PRJNA207329

REPOSITORIES: GEO

ACCESS DATA

Similar Datasets

Project description:Although Candida albicans and Candida dubliniensis are most closely related, both species significantly behave differently with respect to morphogenesis and virulence. In order to gain further insight into the divergent routes for morphogenetic adaptation in both species, we investigated qualitative along with quantitative differences in the transcriptomes of both organisms by cDNA deep sequencing. Following genome-associated assembly of sequence reads we were able to generate experimentally verified databases containing 6016 and 5972 genes for C. albicans and C. dubliniensis, respectively. About 95% of the transcriptionally active regions (TARs) contain open reading frames while the remaining TARs most likely represent non-coding RNAs. Comparison of our annotations with publically available gene models for C. albicans and C. dubliniensis confirmed approximately 95% of already predicted genes, but also revealed so far unknown novel TARs in both species. Qualitative cross-species analysis of these databases revealed in addition to 5802 orthologs also 399 and 49 species-specific protein coding genes for C. albicans and C. dubliniensis, respectively. Furthermore, quantitative transcriptional profiling using RNA-Seq revealed significant differences in the expression of orthologs across both species. We defined a core subset of 84 hyphal-specific genes required for both species, as well as a set of 42 genes that seem to be specifically induced during hyphal morphogenesis in C. albicans. Species specific adaptation in C. albicans and C. dubliniensis is governed by individual genetic repertoires but also by altered regulation of conserved orthologs on the transcriptional level. We investigated qualitative along with quantitative differences in the transcriptomes of both organisms by cDNA deep sequencing. In a first step, we reevaluated the in silico predicted gene models by collecting experimental data using FLX - technology for sequencing strand-specific and normalized cDNA libraries derived from blastospores and hyphae. In the second step, quantitative RNA-Seq (GAIIX) was applied to C. albicans hyphal cells and C. dubliniensis blastospore and hyphal cells to complement reevaluation of the gene models with FLX data as well as to measure differential gene expression across the species with two biological replicates.

Project description:Fusarium graminearum and F. verticillioides are devastating cereal pathogens with very different life history and ecological characteristics. F. graminearum is homothallic, and sexual spores are an important component of its life cycle, responsible for disease initiation. F. verticilloides is heterothallic, and produces only modest numbers of fruiting bodies, which are not a significant source of inoculum. To identify corresponding differences in the transcriptional program underlying fruiting body development in the two species, comparative expression was performed, analyzing six developmental stages. To accompany the transcriptional analysis, detailed morphological characterization of F. verticillioides development was performed and compared to a previous morphological analysis of F. graminearum. Morphological development was similar between the two species, except for the observation of possible trichogynes in F. verticillioides ascogonia, which have not been previously reported for any Fusarium species. Expression of over 9000 orthologous genes were measured for the two species. Functional assignments of highly expressed orthologous genes at each time-point revealed the majority of highly expressed genes fell into the M-bM-^@M-^XM-bM-^@M-^Xunclassified proteinsM-bM-^@M-^YM-bM-^@M-^Y category, reflecting the lack of characterization of genes for sexual development in both species. Simultaneous examination of morphological development and stage-specific gene expression suggests that degeneration of the paraphyses during sexual development is an apoptotic process. Expression of mating type genes in the two species differed, possibly reflecting the divergent roles they play in sexual development. Overall, the differences in gene expression reflect the greater role of fruiting bodies in the life cycle and ecology of F. graminearum versus F. verticillioides. mRNA were sampled and compared from six time points across sexual reproduction in two Fusarium species

Dataset Information

Cross-species gene expression analysis of species-specific differences in preclinical assessment of pharmaceutical compounds (rat)

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure