Proposal for a 6-month internship in 2022 (Master 2 degree): Analysis and integration of RNAseq data to model fetal-maternal interactions at the end of gestation (pig model)

Job Type: 
Stage Master 2

Co-encadrement :
Laurence Liaubet
Agnès Bonnet

Laboratoire INRAE GenPhySE, 31326 Castanet-Tolosan
Equipe Genorobust

Context: CO-LOcATION project (funding: ANR)
The substantial increase in pre-weaning piglet mortality is a major concern in pig production. The most critical period is the perinatal period, essentially the first 24 hours after birth. The high mortality of piglets represents a significant economic loss as well as an ethical problem with regard to animal welfare. The early mortality of piglets depends greatly on their maturity at birth, which is acquired at the end of gestation. In particular, fetal-maternal interactions regulate the distribution of resources between mother and fetus, impacting its development and future health.

The objective of this project is to analyze the transcriptomic data obtained on two tissues in direct contact, the endometrium (maternal tissue) and the placenta (fetal tissue) from 224 fetuses. The experimental set-up comprises samples taken at two stages of late gestation, 90 days and 110 days, the birth being at 114 days in pigs. Fetuses are classified into three maturity categories and around twenty phenotypic measurements are associated with them. The sows are of two different genotypes, Large White (LW) whose piglets are more prone to high neonatal mortality and Meishan (MS) whose more robust piglets show little or no mortality at birth. Among the 224 fetuses, there are also crossed fetuses of mother LW and father MS (MSLW) or mother MS and father LW (LWMS).

Objective of the internship
Thanks to this original experimental model and from RNAseq data, the student will participate in the following objectives:
• Identify the genes expressed in each tissues,
• Identify the differential genes between stages, genotypes and degree of maturity for each tissue,
• Identify the differential genes for the stage x genotype interaction to characterize the biological mechanisms related to a more optimal development of MS compared to LW.
• Study the correlations between the genes expressed and the phenotypes of the fetuses for each tissue.
Next, covariations between the two tissues will be sought in order to characterize groups of genes that can describe the exchange of information between the two maternal and fetal tissues.

Statistical processing: Initially, unsupervised (PCA, classification, CAH) and supervised (PLS-DA) data explorations will be carried out as well as linear models to identify the differential genes in response to the various questions. Then, data integration methods will be used to highlight relationships between the different datasets (PLS methods). All analyzes will be done with R software (RStudio); special attention should be paid to producing readable and commented R codes (R Markdown).
Functional annotation will be realized by search for significant enrichments in different databases (Gene Ontologies, KEGG, …).

Scientific Keywords: feto-maternal interaction, placenta, endometrium, maturity, birth survival
Technical Keywords: RNAseq, linear mixed models, data integration, multivariate methods, systems biology
Level: M2 master’s degree in data analysis, bioinformatics, systems biology.
Skills: statistics, bioinformatics, mastery of R software, systems biology
Duration and period: 6 months

Some references:
Lefort G, Servien R, Quesnel H, Billon Y, Canario L, Iannuccelli N, Canlet C, Paris A, Vialaneix N, Liaubet L. The maturity in fetal pigs using a multi-fluid metabolomic approach. Sci Rep. 2020 Nov 16;10(1):19912. doi: 10.1038/s41598-020-76709-8.

Gondret F, Guével B, Père MC, Quesnel H, Billon Y, Com E, Canario L, Louveau I, Liaubet L. Proteomic analysis of adipose tissue during the last weeks of gestation in pure and crossbred Large White or Meishan fetuses gestated by sows of either breed. J Anim Sci Biotechnol. 2018 Apr 3;9:28. doi: 10.1186/s40104-018-0244-2.

Voillet V, San Cristobal M, Père MC, Billon Y, Canario L, Liaubet L, Lefaucheur L. Integrated Analysis of Proteomic and Transcriptomic Data Highlights Late Fetal Muscle Maturation Process. Mol Cell Proteomics. 2018 Apr;17(4):672-693. doi: 10.1074/mcp.M116.066357.

Yao Y, Voillet V, Jegou M, SanCristobal M, Dou S, Romé V, Lippi Y, Billon Y, Père MC, Boudry G, Gress L, Iannucelli N, Mormède P, Quesnel H, Canario L, Liaubet L, Le Huërou-Luron I. Comparing the intestinal transcriptome of Meishan and Large White piglets during late fetal development reveals genes involved in glucose and lipid metabolism and immunity as valuable clues of intestinal maturity. BMC Genomics. 2017 Aug 22;18(1):647. doi: 10.1186/s12864-017-4001-2.

Voillet V, SanCristobal M, Lippi Y, Martin PG, Iannuccelli N, Lascor C, Vignoles F, Billon Y, Canario L, Liaubet L. Muscle transcriptomic investigation of late fetal development identifies candidate genes for piglet maturity. BMC Genomics. 2014 Sep 17;15(1):797. doi: 10.1186/1471-2164-15-797.


Laurence Liaubet

Laurence dot Liaubet at inra dot fr