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Integrative network analysis on the nutrigenomic control of reproductive development in cattle
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Abstract
Advancements in next generation sequencing technologies have greatly increased our understanding and capability in
deciphering the complex molecular control regulating important biological traits in cattle. More recently efforts have
been focused towards evaluating ‘omics’ datasets, (genomic, transcriptomic, proteomic), in unison, through systems
biology based analytical approaches. Such integrative analyses allow for a more comprehensive evaluation of the
underlying biology governing traits of interest, determining discrete relationships between genes towards a particular
trait as opposed to merely focusing on genes with the largest difference, evident through differential expression analysis
alone. Moreover, through gene co-expression analyses, networks of highly correlated genes may be derived, with the
additional utility of identifying ‘hub genes’. Hub genes are of particular interest as such genes are key to the regulation
of additional genes within a network and thus are key to controlling the expression of a particular trait. Furthermore,
the importance of hub genes to the regulation of a particular trait may not be apparent through differential expression
analyses alone, thus highlighting the functionality of gene co-expression analyses. Additionally, through the integration
of various types of genomic data, for example, genetic and transcriptomic, the functional role of specific SNPs may be
evaluated, based on the interaction between genes harbouring SNPs and the larger co-expression network. Recently,
we have applied such integrative molecular analyses towards deciphering the effect of enhanced nutritional status
on the regulation of reproductive development in prepubertal cattle. Transcriptomic and proteomic data from tissues
of the hypothalamic-pituitary-testicular (HPT) signalling axis were integrated. In particular a putative role of the
miR-2419 miRNA towards reproductive development within the HPT tissues of bull calves was apparent through
enrichment of processes related to metabolism, GnRH signalling, and cholesterol biosynthesis across tissues of the
HPT axis. Knowledge derived from such analyses may be used to identify more accurate genomic targets within the
context of genomically assisted breeding programs.