Biology subjects

Porto-Neto, L. R.

Publications and source records attributed to Porto-Neto, L. R..

4 recordsLinked to original sources

bioRxiv2021

Correlation scan: identifying genomic regions that affect genetic correlations applied to fertility traits

Reproductive traits are often genetically correlated. Yet, we dont fully understand the complexities, synergism, or trade-offs between male and female fertility. Here, we introduce correlation scan, a novel framework for identifying the drivers or antagonizers of the genetic correlation between male and female fertility traits across the bovine genome. The identification of these regions facilitates the understanding of the complexity of these traits. Although the methodology was applied to cattle phenotypes, using high-density SNP genotypes, the general framework developed can be applied to any species or traits, and it can easily accommodate genome sequence data.

genetics↗

bioRxiv2020

Genome-wide co-expression distributions as a metric to prioritize genes of functional importance

Genome-wide gene expression is routinely used as a tool to gain a systems-level understanding of complex, biological processes. Numerical approaches that have been used to highlight influential genes include abundance, differential expression, differential variation, network connectivity and differential connectivity. Network connectivity tends to be built on a small subset of extremely high co-expression signals that are deemed significant, but this overlooks the vast majority of pairwise signals. Here, we aimed to assess a complementary strategy, namely whether the entire shape of the distribution of genome-wide co-expression values contains a meaningful biological signal that has hitherto remained hidden from view. We have developed a computational pipeline to assign one of 8 distributions (including normal, skewed, bimodal, kurtotic, inverted) to every gene. We then used a hypergeometric enrichment process to determine if particular genes (regulators versus non-regulators) and properties (differentially expressed or not) tend to be associated with particular distributions greater than would be expected by chance. Examination of several distinct data sets spanning 4 species indicates that there is indeed an additional biological signal present in the genome-wide distribution of co-expression values which would be overlooked by currently adopted approaches. Author summaryHigh-throughput technologies, such as RNA-Seq, enables access to a vast amount of data. Here, we describe a new approach to interrogate these data and extract further information to help researchers to understand complex phenotypes. Our method is based on gene-level co-expression distributions which were compared to eight possible template shapes to group genes with similar behaviours. The method was tested using five different datasets and the consistency of the results indicate it can be used as a complementary strategy to analyse transcriptomic data.

bioinformatics↗

bioRxiv2019

Association analysis of loci implied in “buffering” epistasis

The existence of buffering mechanisms is an emerging property of biological networks, and this results in the possible existence of \"buffering\" loci, that would allow buildup of robustness through evolution. So far, there are no explicit methods to find loci implied in buffering mechanisms. However, buffering can be seen as interaction with genetic background. Here we develop this idea into a tractable model for quantitative genetics, in which the buffering effect of one locus with many other loci is condensed into a single (statistical) effect, multiplicative on the total (statistical) additive genetic effect. This allows easier interpretation of the results, and it also simplifies the problem of detecting epistasis from quadratic to linear in the number of loci. Armed with this formulation, we construct a linear model for genome-wide association studies that estimates, and declares significance, of multiplicative epistatic effects at single loci. The model has the form of a variance components, norm reaction model and likelihood ratio tests are used for significance. This model is a generalization and explanation of previous ones. We then test our model using bovine data: Brahman and Tropical Composite animals, phenotyped for body weight at yearling and genotyped up to [~]770,000 Single Nucleotide Polymorphisms (SNP). After association analysis and based on False Discovery Rate rules, we find a number of loci with buffering action in one, the other, or both breeds; these loci do not have significant statistical additive effect. Most of these loci have been reported in previous studies, either with an additive effect, or as footprints of selection. We identify epistatic SNPs present in or near genes encoding for proteins that are functionally enriched for peptide activity and transcription factors reported in the context of signatures of selection in multi-breed cattle population studies. These include loci known to be associated with coat color, fertility and adaptation to tropical environments. In these populations we found loci that have a non-significant statistical additive effect but a significant epistatic effect. We argue that the discovery and study of loci associated with buffering effects allows attacking the difficult problems, among others, of release of maintenance variance in artificial and natural selection, of quick adaptation to the environment, and of opposite signs of marker effects in different backgrounds. We conclude that our method and our results generate promising new perspectives for research in evolutionary and quantitative genetics based on the study of loci that buffer effect of other loci.

genetics↗

bioRxiv2018

Systems biology reveals NR2F6 and TGFB1 as key regulators of feed efficiency in beef cattle

Systems biology approaches are used as strategy to uncover tissue-specific perturbations and regulatory genes related to complex phenotypes. We applied this approach to study feed efficiency (FE) in beef cattle, an important trait both economically and environmentally. Poly-A selected RNA of five tissues (adrenal gland, hypothalamus, liver, skeletal muscle and pituitary) of eighteen young bulls, selected for high and low FE, were sequenced (100bp, pared-end). From the 17,354 expressed genes, 1,317 were prioritized by five selection categories (differentially expressed, harbouring SNPs associated with FE, tissue-specific, secreted in plasma and key regulators) and used for network construction. NR2F6 and TGFB were identified and validated by motif discovery as key regulators of hepatic inflammatory response and muscle tissue development, respectively, two biological processes demonstrated to be associated to FE. Moreover, we indicated potential biomarkers of FE which are related to hormonal control of metabolism and sexual maturity. By using robust methodologies and validation strategies, we confirmed main biological processes related to FE in Bos indicus and indicated candidate genes as regulators or biomarkers of superior animals.

systems biology↗