BackgroundAnimal’s efficiency in converting feed into lean gain is a critical issue for the profitability of meat industries. This study aimed to describe shared and specific molecular responses in different tissues of pigs divergently selected over eight generations for residual feed intake (RFI).ResultsPigs from the low RFI line had an improved gain-to-feed ratio during the test period and displayed higher leanness but similar adiposity when compared with pigs from the high RFI line at 132 days of age. Transcriptomics data were generated from longissimus muscle, liver and two adipose tissues using a porcine microarray and analyzed for the line effect (n = 24 pigs per line). The most apparent effect of the line was seen in muscle, whereas subcutaneous adipose tissue was the less affected tissue. Molecular data were analyzed by bioinformatics and subjected to multidimensional statistics to identify common biological processes across tissues and key genes participating to differences in the genetics of feed efficiency. Immune response, response to oxidative stress and protein metabolism were the main biological pathways shared by the four tissues that distinguished pigs from the low or high RFI lines. Many immune genes were under-expressed in the four tissues of the most efficient pigs. The main genes contributing to difference between pigs from the low vs high RFI lines were CD40, CTSC and NTN1. Different genes associated with energy use were modulated in a tissue-specific manner between the two lines. The gene expression program related to glycogen utilization was specifically up-regulated in muscle of pigs from the low RFI line (more efficient). Genes involved in fatty acid oxidation were down-regulated in muscle but were promoted in adipose tissues of the same pigs when compared with pigs from the high RFI line (less efficient). This underlined opposite line-associated strategies for energy use in skeletal muscle and adipose tissue. Genes related to cholesterol synthesis and efflux in liver and perirenal fat were also differentially regulated in pigs from the low vs high RFI lines.ConclusionsNon-productive functions such as immunity, defense against pathogens and oxidative stress contribute likely to inter-individual variations in feed efficiency.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-017-3639-0) contains supplementary material, which is available to authorized users.
BackgroundBecause the cost of cereals is unstable and represents a large part of production charges for meat-type chicken, there is an urge to formulate alternative diets from more cost-effective feedstuff. We have recently shown that meat-type chicken source is prone to adapt to dietary starch substitution with fat and fiber. The aim of this study was to better understand the molecular mechanisms of this adaptation to changes in dietary energy sources through the fine characterization of transcriptomic changes occurring in three major metabolic tissues – liver, adipose tissue and muscle – as well as in circulating blood cells.ResultsWe revealed the fine-tuned regulation of many hepatic genes encoding key enzymes driving glycogenesis and de novo fatty acid synthesis pathways and of some genes participating in oxidation. Among the genes expressed upon consumption of a high-fat, high-fiber diet, we highlighted CPT1A, which encodes a key enzyme in the regulation of fatty acid oxidation. Conversely, the repression of lipogenic genes by the high-fat diet was clearly associated with the down-regulation of SREBF1 transcripts but was not associated with the transcript regulation of MLXIPL and NR1H3, which are both transcription factors. This result suggests a pivotal role for SREBF1 in lipogenesis regulation in response to a decrease in dietary starch and an increase in dietary PUFA. Other prospective regulators of de novo hepatic lipogenesis were suggested, such as PPARD, JUN, TADA2A and KAT2B, the last two genes belonging to the lysine acetyl transferase (KAT) complex family regulating histone and non-histone protein acetylation. Hepatic glycogenic genes were also down-regulated in chickens fed a high-fat, high-fiber diet compared to those in chickens fed a starch-based diet. No significant dietary-associated variations in gene expression profiles was observed in the other studied tissues, suggesting that the liver mainly contributed to the adaptation of birds to changes in energy source and nutrients in their diets, at least at the transcriptional level. Moreover, we showed that PUFA deposition observed in the different tissues may not rely on transcriptional changes.ConclusionWe showed the major role of the liver, at the gene expression level, in the adaptive response of chicken to dietary starch substitution with fat and fiber.Electronic supplementary materialThe online version of this article (10.1186/s12864-018-4520-5) contains supplementary material, which is available to authorized users.
BackgroundIn the context of high-throughput molecular data analysis it is common that the observations included in a dataset form distinct groups; for example, measured at different times, under different conditions or even in different labs. These groups are generally denoted as batches. Systematic differences between these batches not attributable to the biological signal of interest are denoted as batch effects. If ignored when conducting analyses on the combined data, batch effects can lead to distortions in the results. In this paper we present FAbatch, a general, model-based method for correcting for such batch effects in the case of an analysis involving a binary target variable. It is a combination of two commonly used approaches: location-and-scale adjustment and data cleaning by adjustment for distortions due to latent factors. We compare FAbatch extensively to the most commonly applied competitors on the basis of several performance metrics. FAbatch can also be used in the context of prediction modelling to eliminate batch effects from new test data. This important application is illustrated using real and simulated data. We implemented FAbatch and various other functionalities in the R package bapred available online from CRAN.ResultsFAbatch is seen to be competitive in many cases and above average in others. In our analyses, the only cases where it failed to adequately preserve the biological signal were when there were extremely outlying batches and when the batch effects were very weak compared to the biological signal.ConclusionsAs seen in this paper batch effect structures found in real datasets are diverse. Current batch effect adjustment methods are often either too simplistic or make restrictive assumptions, which can be violated in real datasets. Due to the generality of its underlying model and its ability to perform well FAbatch represents a reliable tool for batch effect adjustment for most situations found in practice.Electronic supplementary materialThe online version of this article (doi:10.1186/s12859-015-0870-z) contains supplementary material, which is available to authorized users.
Supplementary data are available at Bioinformatics online.
BackgroundMicroarray technology allows the simultaneous analysis of thousands of genes within a single experiment. Significance analyses of transcriptomic data ignore the gene dependence structure. This leads to correlation among test statistics which affects a strong control of the false discovery proportion. A recent method called FAMT allows capturing the gene dependence into factors in order to improve high-dimensional multiple testing procedures. In the subsequent analyses aiming at a functional characterization of the differentially expressed genes, our study shows how these factors can be used both to identify the components of expression heterogeneity and to give more insight into the underlying biological processes.ResultsThe use of factors to characterize simple patterns of heterogeneity is first demonstrated on illustrative gene expression data sets. An expression data set primarily generated to map QTL for fatness in chickens is then analyzed. Contrarily to the analysis based on the raw data, a relevant functional information about a QTL region is revealed by factor-adjustment of the gene expressions. Additionally, the interpretation of the independent factors regarding known information about both experimental design and genes shows that some factors may have different and complex origins.ConclusionsAs biological information and technological biases are identified in what was before simply considered as statistical noise, analyzing heterogeneity in gene expression yields a new point of view on transcriptomic data.
The R package FAMT (factor analysis for multiple testing) provides a powerful method for large-scale significance testing under dependence. It is especially designed to select differentially expressed genes in microarray data when the correlation structure among gene expressions is strong. Indeed, this method reduces the negative impact of dependence on the multiple testing procedures by modeling the common information shared by all the variables using a factor analysis structure. New test statistics for general linear contrasts are deduced, taking advantage of the common factor structure to reduce correlation and consequently the variance of error rates. Thus, the FAMT method shows improvements with respect to most of the usual methods regarding the non discovery rate and the control of the false discovery rate (FDR). The steps of this procedure, each of them corresponding to R functions, are illustrated in this paper by two microarray data analyses. We first present how to import the gene expression data, the covariates and gene annotations. The second step includes the choice of the optimal number of factors, the factor model fitting, and provides a list of selected genes according to a preset FDR control level. Finally, diagnostic plots are provided to help the user interpret the factors using available external information on either genes or arrays.
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