TY - JOUR
T1 - Integrative analysis of multi-omics data reveals importance of collagen and the PI3K AKT signalling pathway in CAKUT
AU - Bayjanov, Jumamurat R.
AU - Doornbos, Cenna
AU - Ozisik, Ozan
AU - Shin, Woosub
AU - Queralt-Rosinach, Núria
AU - Wijnbergen, Daphne
AU - Saulnier-Blache, Jean Sébastien
AU - Schanstra, Joost P.
AU - Buffin-Meyer, Bénédicte
AU - Klein, Julie
AU - Fernández, José M.
AU - Kaliyaperumal, Rajaram
AU - Baudot, Anaïs
AU - ’t Hoen, Peter A.C.
AU - Ehrhart, Friederike
N1 - Funding Information:
The authors would like to thank Matthias Haimel, Laura Rodriguez-Navas, Franz Sch\u00E4fer, Nazli Sila Kara, Ugur Sezerman, Ana Rath, and Chris Evelo for helpful discussions, and the anDREa team for technical support. This work is funded by the European Union\u2019s Horizon 2020 research and innovation programme under the EJP RD COFUND-EJP N\u00B0 825575. OOs work is supported by the Excellence Initiative of Aix-Marseille University\u2014A*Midex, a French \u201CInvestissements d\u2019Avenir\u201D programme. BBM, JK, JS, and JSB\u2019s part of the work was financed by the French \u201CProgramme Hospitalier de Recherche Clinique\u201D (PHRC) number N\u00B0 10 138 01\u2014N\u00B0 RCB 2010-AO1151-38, by Grants from the \"Fondation pour la Recherche M\u00E9dicale\" (Grant number DEQ20170336759), and by the European Commission Seventh Framework Programme (FP7/2007-2013) grant agreement no. 305608 (EURenOmics). BBM is supported by \"Agence de la Biom\u00E9decine\" (METAPhOR project).
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12/1
Y1 - 2024/12/1
N2 - Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is the leading cause of childhood chronic kidney failure and a significant cause of chronic kidney disease in adults. Genetic and environmental factors are known to influence CAKUT development, but the currently known disease mechanism remains incomplete. Our goal is to identify affected pathways and networks in CAKUT, and thereby aid in getting a better understanding of its pathophysiology. With this goal, the miRNome, peptidome, and proteome of over 30 amniotic fluid samples of patients with non-severe CAKUT was compared to patients with severe CAKUT. These omics data sets were made findable, accessible, interoperable, and reusable (FAIR) to facilitate their integration with external data resources. Furthermore, we analysed and integrated the omics data sets using three different bioinformatics strategies: integrative analysis with mixOmics, joint dimensionality reduction and pathway analysis. The three bioinformatics analyses provided complementary features, but all pointed towards an important role for collagen in CAKUT development and the PI3K-AKT signalling pathway. Additionally, several key genes (CSF1, IGF2, ITGB1, and RAC1) and microRNAs were identified. We published the three analysis strategies as containerized workflows. These workflows can be applied to other FAIR data sets and help gaining knowledge on other rare diseases.
AB - Congenital Anomalies of the Kidney and Urinary Tract (CAKUT) is the leading cause of childhood chronic kidney failure and a significant cause of chronic kidney disease in adults. Genetic and environmental factors are known to influence CAKUT development, but the currently known disease mechanism remains incomplete. Our goal is to identify affected pathways and networks in CAKUT, and thereby aid in getting a better understanding of its pathophysiology. With this goal, the miRNome, peptidome, and proteome of over 30 amniotic fluid samples of patients with non-severe CAKUT was compared to patients with severe CAKUT. These omics data sets were made findable, accessible, interoperable, and reusable (FAIR) to facilitate their integration with external data resources. Furthermore, we analysed and integrated the omics data sets using three different bioinformatics strategies: integrative analysis with mixOmics, joint dimensionality reduction and pathway analysis. The three bioinformatics analyses provided complementary features, but all pointed towards an important role for collagen in CAKUT development and the PI3K-AKT signalling pathway. Additionally, several key genes (CSF1, IGF2, ITGB1, and RAC1) and microRNAs were identified. We published the three analysis strategies as containerized workflows. These workflows can be applied to other FAIR data sets and help gaining knowledge on other rare diseases.
U2 - 10.1038/s41598-024-71721-8
DO - 10.1038/s41598-024-71721-8
M3 - Article
SN - 2045-2322
VL - 14
JO - Scientific Reports
JF - Scientific Reports
IS - 1
M1 - 20731
ER -