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Large-Scale Automatic Feature Selection for Biomarker Discovery in High-Dimensional OMICs Data
No full textThe identification of biomarker signatures in omics molecular profiling is usually performed to predict outcomes in a precision medicine context, such as patient disease susceptibility, diagnosis, prognosis, and treatment response. To identify these signatures, we have developed a biomarker discovery tool, called BioDiscML. From a collection of samples and their associated characteristics, i.e., the biomarkers (e.g., gene expression, protein levels, clinico-pathological data), BioDiscML exploits various feature selection procedures to produce signatures associated to machine learning models that will predict efficiently a specified outcome. To this purpose, BioDiscML uses a large variety of machine learning algorithms to select the best combination of biomarkers for predicting categorical or continuous outcomes from highly unbalanced datasets. The software has been implemented to automate all machine learning steps, including data pre-processing, feature selection, model selection, and performance evaluation. BioDiscML is delivered as a stand-alone program and is available for download at https://github.com/mickaelleclercq/BioDiscML
The Influence of Contrasting Microbial Lifestyles on the Pre-symbiotic Metabolite Responses of Eucalyptus grandis Roots
No full textPlant roots co-inhabit the soil with a diverse consortium of microbes of which a number attempt to enter symbiosis with the plant. These microbes may be pathogenic, mutualistic, or commensal. Hence, the health and survival of plants is heavily reliant on their ability to perceive different microbial lifestyles and respond appropriately.[br/]
Emerging research suggests that there is a pivotal role for plant root secondary metabolites in responding to microbial colonization. However, it is largely unknown if plants are able to differentiate between microbes of different lifestyles and respond differently during the earliest stages of pre-symbiosis (i.e., prior to physical contact).[br/]
In studying plant responses to a range of microbial isolates, we questioned: (1) if individual microbes of different lifestyles and species caused alterations to the plant root metabolome during pre-symbiosis, and (2) if these early metabolite responses correlate with the outcome of the symbiotic interaction in later phases of colonization.
We compared the changes of the root tip metabolite profile of the model tree Eucalyptus grandis during pre-symbiosis with two isolates of a pathogenic fungus (Armillaria luteobubalina), one isolate of a pathogenic oomycete (Phytophthora cinnamomi), two isolates of an incompatible mutualistic fungus (Suillus granulatus), and six isolates of a compatible mutualistic fungus (Pisolithus microcarpus).[br/]
Untargeted metabolite profiling revealed predominantly positive root metabolite responses at the pre-symbiosis stage, prior to any observable phenotypical changes of the root tips. Metabolite responses in the host tissue that were specific to each microbial species were identified. A deeper analysis of the root metabolomic profiles during pre-symbiotic contact with six strains of P. microcarpus showed a connection between these early metabolite responses in the root with later colonization success.[br/]
Further investigation using isotopic tracing revealed a portion of metabolites found in root tips originated from the fungus. RNA-sequencing also showed that the plant roots undergo complementary transcriptomic reprogramming in response to the fungal stimuli.[br/]
Taken together, our results demonstrate that the early metabolite responses of plant roots are partially selective toward the lifestyle of the interacting microbe, and that these responses can be crucial in determining the outcome of the interaction
Bacteroidetes use thousands of enzyme combinations to break down glycans
No full textUnlike proteins, glycan chains are not directly encoded by DNA, but by the specificity of the enzymes that assemble them. Theoretical calculations have proposed an astronomical number of possible isomers (>10(12) hexasaccharides) but the actual diversity of glycan structures in nature is not known. Bacteria of the Bacteroidetes phylum are considered primary degraders of polysaccharides and they are found in all ecosystems investigated. In Bacteroidetes genomes, carbohydrate-degrading enzymes (CAZymes) are arranged in gene clusters termed polysaccharide utilization loci (PULs). The depolymerization of a given complex glycan by Bacteroidetes PULs requires bespoke enzymes; conversely, the enzyme composition in PULs can provide information on the structure of the targeted glycans. Here we group the 13,537 PULs encoded by 964 Bacteroidetes genomes according to their CAZyme composition. We find that collectively Bacteroidetes have elaborated a few thousand enzyme combinations for glycan breakdown, suggesting a global estimate of diversity of glycan structures much smaller than the theoretical one
Relative effects of location relative to the corpus luteum and lactation on the transcriptome of the bovine oviduct epithelium
No full textBackgroundLactation and associated metabolic stresses during the post-partum period have been shown to impair fertility in dairy cows. The oviduct plays key roles in embryo development and the establishment of pregnancy in cattle. The aim of this study was to investigate the effects of lactation and location relative to the corpus luteum (CL) on the transcriptome of the bovine oviduct epithelium.ResultsAn original animal model was used. At 60days post-partum, Holstein lactating (n=4) and non-lactating (i.e. never milked after calving; n=5) cows, as well as control nulliparous heifers (n=5), were slaughtered on Day 3 following induced estrus, and epithelial samples from the oviductal ampulla and isthmus ipsilateral and contralateral to the corpus luteum (CL) were recovered for RNA sequencing. In the oviduct ipsilateral to the CL, differentially expressed genes (DEGs) were identified between heifers compared with both postpartum cow groups. However, only 15 DEGs were identified between post-partum lactating and non-lactating cows in the ipsilateral isthmus and none were identified in the ipsilateral ampulla. In contrast, 192 and 2583 DEGs were identified between ipsilateral and contralateral ampulla and isthmus, respectively. In both regions, more DEGs were identified between ipsilateral and contralateral oviducts in non-lactating cows and heifers than in lactating cows. Functional annotation of the DEGs associated with comparisons between metabolic groups highlighted a number of over-represented biological functions and cell pathways including immune response and cholesterol/steroid biosynthesis.ConclusionsGene expression in the oviduct epithelium, particularly in the isthmus, was more affected by the location relative to the CL than by lactation at Day 3 post-estrus. Furthermore, the effect of the proximity to the CL was modulated by the metabolic status of the cow
Trout myomaker contains 14 minisatellites and two sequence extensions but retains fusogenic function
No full textThe formation of new myofibers in vertebrates occurs by
myoblast fusion and requires fusogenic activity of the musclespecific membrane protein myomaker. Here, using in silico
(BLAST) genome analyses, we show that the myomaker gene
from trout includes 14 minisatellites, indicating that it has an
unusual structure compared with those of other animal species.
We found that the trout myomaker gene encodes a 434–amino
acid (aa) protein, in accordance with its apparent molecular
mass (40 kDa) observed by immunoblotting. The first half of
the trout myomaker protein (1–220 aa) is similar to the 221-aa
mouse myomaker protein, whereas the second half (222–234 aa)
does not correspond to any known motifs and arises from two
protein extensions. The first extension (70 aa) apparently
appeared with the radiation of the bony fish clade Euteleostei,
whereas the second extension (up to 236 aa) is restricted to the
superorder Protacanthopterygii (containing salmonids and
pike) and corresponds to the insertion of minisatellites having a
length of 30 nucleotides. According to gene expression analyses,
trout myomaker expression is consistently associated with the
formation of new myofibers during embryonic development,
postlarval growth, and muscle regeneration. Using cell-mixing
experiments, we observed that trout myomaker has retained the
ability to drive the fusion of mouse fibroblasts with C2C12 myoblasts. Our work reveals that trout myomaker has fusogenic
function despite containing two protein extensions
Correction to: Quantitative trait loci for resistance to Flavobacterium psychrophilum in rainbow trout: effect of the mode of infection and evidence of epistatic interactions
No full textSociel - La durabilité sociale des exploitations d'élevage dans leurs territoires.
No full textLa dimension sociale des exploitations d’élevage est nettement moins documentée que les dimensions
économique et environnementale. Nous proposons, à travers le projet Sociel, un cadre pour analyser la
durabilité sociale construit à partir des propos d'une trentaine d'éleveurs et d'autant d'acteurs provenant
de quatre petites régions contrastées (montagne, pastorale, polyculture–élevage périurbaine), pour tenir
compte de sa nature subjective et située. Ce projet, en s’organisant autour de sept grands volets
imbriqués les uns aux autres et en croisant des faits avec les ressentis des interviewés, permet
d’aborder la durabilité sociale des exploitations dans leur territoire en éclairant sa complexité. La
dimension sociale concerne l’individu, la famille mais aussi des collectifs plus larges. Elle s’intéresse à
la vie professionnelle mais aussi à la vie privée, à la participation des exploitations à la vitalité
territoriale, et à leur transmissibilité. Les débats auprès d’éleveurs, de conseillers, d’enseignants et
d’acteurs locaux confirment l'importance de cette dimension pour dessiner les avenirs de l'élevage.The social dimension of farm sustainability is significantly less well documented than the economic and
environmental ones. We propose a framework to analyze it, built on the words and feelings of thirty
breeders and as many other actors from four contrasting small regions to take into account its subjective
and context dependent nature. Organized around seven major intertwined sections, facts are crossed
with the feelings of the interviewees. By this way, such framework makes it possible to address the
social sustainability of farms in their territory by enlightening its complexity. This dimension of
sustainability concerns the individual, the family but also broader collectives. It deals also with
professional and private life, farms involvement in territorial vitality and farms transfer to other partners
or generation. Discussions with breeders, advisors, teachers and local actors confirm the importance of
this social dimension to draw the future of livestock
Sequence-based GWAS, network and pathway analyses reveal genes co-associated with milk cheese-making properties and milk composition in Montbéliarde cows
No full textBACKGROUND:
Milk quality in dairy cattle is routinely assessed via analysis of mid-infrared (MIR) spectra; this approach can also be used to predict the milk's cheese-making properties (CMP) and composition. When this method of high-throughput phenotyping is combined with efficient imputations of whole-genome sequence data from cows' genotyping data, it provides a unique and powerful framework with which to carry out genomic analyses. The goal of this study was to use this approach to identify genes and gene networks associated with milk CMP and composition in the Montbéliarde breed.
RESULTS:
Milk cheese yields, coagulation traits, milk pH and contents of proteins, fatty acids, minerals, citrate, and lactose were predicted from MIR spectra. Thirty-six phenotypes from primiparous Montbéliarde cows (1,442,371 test-day records from 189,817 cows) were adjusted for non-genetic effects and averaged per cow. 50 K genotypes, which were available for a subset of 19,586 cows, were imputed at the sequence level using Run6 of the 1000 Bull Genomes Project (comprising 2333 animals). The individual effects of 8.5 million variants were evaluated in a genome-wide association study (GWAS) which led to the detection of 59 QTL regions, most of which had highly significant effects on CMP and milk composition. The results of the GWAS were further subjected to an association weight matrix and the partial correlation and information theory approach and we identified a set of 736 co-associated genes. Among these, the well-known caseins, PAEP and DGAT1, together with dozens of other genes such as SLC37A1, ALPL, MGST1, SEL1L3, GPT, BRI3BP, SCD, GPAT4, FASN, and ANKH, explained from 12 to 30% of the phenotypic variance of CMP traits. We were further able to identify metabolic pathways (e.g., phosphate and phospholipid metabolism and inorganic anion transport) and key regulator genes, such as PPARA, ASXL3, and bta-mir-200c that are functionally linked to milk composition.
CONCLUSIONS:
By using an approach that integrated GWAS with network and pathway analyses at the whole-genome sequence level, we propose candidate variants that explain a substantial proportion of the phenotypic variance of CMP traits and could thus be included in genomic evaluation models to improve milk CMP in Montbéliarde cows
