Application of Top-Down and Bottom-up Systems Approaches in Ruminant Physiology and Metabolism

Abstract

Systems biology is a computational field that has been used for several years across different scientific areas of biological research to uncover the complex interactions occurring in living organisms. Applications of systems concepts at the mammalian genome level are quite challenging, and new complimentary computational/experimental techniques are being introduced. Most recent work applying modern systems biology techniques has been conducted on bacteria, yeast, mouse, and human genomes. However, these concepts and tools are equally applicable to other species including ruminants (e.g., livestock). In systems biology, both bottom-up and top-down approaches are central to assemble information from all levels of biological pathways that must coordinate physiological processes. A bottom-up approach encompasses draft reconstruction, manual curation, network reconstruction through mathematical methods, and validation of these models through literature analysis (i.e., bibliomics). Whereas top-down approach encompasses metabolic network reconstructions using ‘omics’ data (e.g., transcriptomics, proteomics) generated through DNA microarrays, RNA-Seq or other modern high-throughput genomic techniques using appropriate statistical and bioinformatics methodologies. In this review we focus on top-down approach as a means to improve our knowledge of underlying metabolic processes in ruminants in the context of nutrition. We also explore the usefulness of tissue specific reconstructions (e.g., liver and adipose tissue) in cattle as a means to enhance productive efficiency.

Systems biology study of mucopolysaccharidosis using a human metabolic reconstruction network

“…Manual curation includes in-depth literature search to ensure high quality and coverage of the reconstruction [32]. These metabolic reconstructions are composed by a stoichiometric matrix that relates enzymes and metabolites substrates with the products of these reactions for a specific organism [32][33][34]. In this sense, these metabolic networks can be defined as large systems of chemical reactions [35].…”

Relative extended haplotype homozygosity signals across breeds reveal dairy and beef specific signatures of selection

“…Selection signals that result from environmental or anthropogenic pressures help us understand the processes that have led to breed formation. These studies are usually conducted with a “top-down” approach [ 3 ], from genotype to phenotype, whereby genomic data are statistically analysed to detect traces/marks/signs of directional selection. In analyses that aim at identifying selection signatures, the phenotype is considered in its broadest sense: breed, production aptitude or even adaptation to a specific environment.…”

Effect of Climate Change on Rice

“…Many previous 'omics' studies, which can reveal highly informative expression patterns of genes/proteins that reflect the differentiation of response among genotypes with contrasting stress tolerance, have been performed to unravel the abiotic stress-responsive mechanisms in plants [50][51][52]. Disclosure of new approach is gaining popularity among the molecular biologist, it is known as top-down approach which involves metabolic network reconstructions using 'omics' data (e.g., transcriptomics, proteomics) generated through DNA microarrays, RNA-Seq or other modern high-throughput genomic techniques using appropriate statistical and bioinformatics methodologies [53].…”