Publications by authors named "Ruggero Barbieri"

4 Publications

  • Page 1 of 1

Inflammation status modulates the effect of host genetic variation on intestinal gene expression in inflammatory bowel disease.

Nat Commun 2021 02 18;12(1):1122. Epub 2021 Feb 18.

Department of Gastroenterology and Hepatology, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

More than 240 genetic risk loci have been associated with inflammatory bowel disease (IBD), but little is known about how they contribute to disease development in involved tissue. Here, we hypothesized that host genetic variation affects gene expression in an inflammation-dependent way, and investigated 299 snap-frozen intestinal biopsies from inflamed and non-inflamed mucosa from 171 IBD patients. RNA-sequencing was performed, and genotypes were determined using whole exome sequencing and genome wide genotyping. In total, 28,746 genes and 6,894,979 SNPs were included. Linear mixed models identified 8,881 independent intestinal cis-expression quantitative trait loci (cis-eQTLs) (FDR < 0.05) and interaction analysis revealed 190 inflammation-dependent intestinal cis-eQTLs (FDR < 0.05), including known IBD-risk genes and genes encoding immune-cell receptors and antibodies. The inflammation-dependent cis-eQTL SNPs (eSNPs) mainly interact with prevalence of immune cell types. Inflammation-dependent intestinal cis-eQTLs reveal genetic susceptibility under inflammatory conditions that can help identify the cell types involved in and the pathways underlying inflammation, knowledge that may guide future drug development and profile patients for precision medicine in IBD.
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http://dx.doi.org/10.1038/s41467-021-21458-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7892863PMC
February 2021

Exome Sequencing in Patient-Parent Trios Suggests New Candidate Genes for Early-onset Primary Sclerosing Cholangitis.

Liver Int 2021 Feb 16. Epub 2021 Feb 16.

University of Groningen, University Medical Center Groningen, Department of Genetics, Groningen, the Netherlands.

Background & Aims: Primary sclerosing cholangitis (PSC) is a rare bile duct disease strongly associated with inflammatory bowel disease (IBD). Whole-exome sequencing (WES) has contributed to understanding the molecular basis of very early-onset IBD, but rare protein-altering genetic variants have not been identified for early-onset PSC. We performed WES in patients diagnosed with PSC ≤ 12 years to investigate the contribution of rare genetic variants to early-onset PSC.

Methods: In this multicenter study, WES was performed on 87 DNA samples from 29 patient-parent trios with early-onset PSC. We selected rare (minor allele frequency < 2%) coding and splice-site variants that matched recessive (homozygous and compound heterozygous variants) and dominant (de novo) inheritance in the index patients. Variant pathogenicity was predicted by an in-house developed algorithm (GAVIN), and PSC-relevant variants were selected using gene expression data and gene function.

Results: In 22 out of 29 trios we identified at least 1 possibly pathogenic variant. We prioritized 36 genes, harboring a total of 54 variants with predicted pathogenic effects. In 18 genes we identified 36 compound heterozygous variants, whereas in the other 18 genes we identified 18 de novo variants. Twelve of 36 candidate risk genes are known to play a role in transmembrane transport, adaptive and innate immunity, and epithelial barrier function.

Conclusions: The 36 candidate genes for early-onset PSC need further verification in other patient cohorts and evaluation of gene function before a causal role can be attributed to its variants.
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http://dx.doi.org/10.1111/liv.14831DOI Listing
February 2021

MOLGENIS research: advanced bioinformatics data software for non-bioinformaticians.

Bioinformatics 2019 03;35(6):1076-1078

Genomics Coordination Center, University of Groningen and University Medical Center Groningen, Groningen, The Netherlands.

Motivation: The volume and complexity of biological data increases rapidly. Many clinical professionals and biomedical researchers without a bioinformatics background are generating big '-omics' data, but do not always have the tools to manage, process or publicly share these data.

Results: Here we present MOLGENIS Research, an open-source web-application to collect, manage, analyze, visualize and share large and complex biomedical datasets, without the need for advanced bioinformatics skills.

Availability And Implementation: MOLGENIS Research is freely available (open source software). It can be installed from source code (see http://github.com/molgenis), downloaded as a precompiled WAR file (for your own server), setup inside a Docker container (see http://molgenis.github.io), or requested as a Software-as-a-Service subscription. For a public demo instance and complete installation instructions see http://molgenis.org/research.
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http://dx.doi.org/10.1093/bioinformatics/bty742DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6419911PMC
March 2019

Proteogenomics: Key Driver for Clinical Discovery and Personalized Medicine.

Adv Exp Med Biol 2016 ;926:21-47

Department of Analytical Biochemistry, Research Institute of Pharmacy, University of Groningen, Antonius Deusinglaan 1, 9713 AV, Groningen, The Netherlands.

Proteogenomics is a multi-omics research field that has the aim to efficiently integrate genomics, transcriptomics and proteomics. With this approach it is possible to identify new patient-specific proteoforms that may have implications in disease development, specifically in cancer. Understanding the impact of a large number of mutations detected at the genomics level is needed to assess the effects at the proteome level. Proteogenomics data integration would help in identifying molecular changes that are persistent across multiple molecular layers and enable better interpretation of molecular mechanisms of disease, such as the causal relationship between single nucleotide polymorphisms (SNPs) and the expression of transcripts and translation of proteins compared to mainstream proteomics approaches. Identifying patient-specific protein forms and getting a better picture of molecular mechanisms of disease opens the avenue for precision and personalized medicine. Proteogenomics is, however, a challenging interdisciplinary science that requires the understanding of sample preparation, data acquisition and processing for genomics, transcriptomics and proteomics. This chapter aims to guide the reader through the technology and bioinformatics aspects of these multi-omics approaches, illustrated with proteogenomics applications having clinical or biological relevance.
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http://dx.doi.org/10.1007/978-3-319-42316-6_3DOI Listing
June 2017