From high-throughput to hypotheses: an integrated, data-driven approach to characterizing hepatic development and metabolic reprogramming in the post-hatch broiler chick
Date
2021
Authors
Journal Title
Journal ISSN
Volume Title
Publisher
University of Delaware
Abstract
Artificial selection of modern meat-producing chickens (broilers) for production characteristics has led to dramatic changes in phenotype, yet the impact of this selection on metabolic and molecular mechanisms is poorly understood. The first three weeks post-hatch represent a critical period of adjustment, during which the yolk lipid is depleted and the bird transitions to reliance on a carbohydrate-rich diet. As the liver is the major organ involved in macronutrient metabolism and nutrient allocation, an approach exploiting two types of high-throughput data (transcriptomics and metabolomics) has been implemented to characterize its development, and molecular fluctuations occurring over this important transition. ☐ • First, with an emphasis on metabolic reprogramming, we compared levels of transcripts and primary metabolites at Day 4 and Day 20 post-hatch, establishing differences in core metabolism. For example, at Day 4, metabolic flexibility allows for efficiency to meet the demands of rapid liver growth under oxygen-limiting conditions. At Day 20, the liver’s metabolism has shifted to process a carbohydrate-rich diet that supports the rapid overall growth of the modern broiler. ☐ • Secondly, we have used an integrated correlation network approach to identify clusters of genes, liver metabolites, and plasma metabolites showing synchronized patterns of abundance over the complete time course, and additionally relating these groups to blood chemistry measurements indicative of metabolic changes. This work exposed more nuanced trends occurring over the time course, and also provided insight into how changes in the liver translate to the system as a whole. ☐ • Lastly, we have developed a dynamic workflow to efficiently screen the entire dataset of over 30 thousand features for relation to a response variable (normalized liver mass), computationally reduce the pool of candidates based on significant association, and confirm supportive evidence for these relationships, culminating in novel and statistically significant predictions. This workflow is simple, scalable, and broadly applicable as a means of data exploration, feature prioritization, and hypothesis generation. ☐ Characterizing the changes associated with normal post-hatch hepatic development in the broiler chicken has generated testable hypotheses about the involvement of specific genes and metabolites, clarified the importance of hypoxia to rapid organ growth, and contributed to our understanding of the molecular changes affected by decades of artificial selection.
Description
Keywords
Metabolomics, Transcriptomics, WGCNA