Biomedical Genomics Group

CNAG-CRG

GROUP LEADER:
Ivo Glynne Gut

POSTDOCTORAL FELLOWS:
Gian-Andri Thun, Miranda Stobbe, Ryoji Takahashi, Justin Whalley (until July)

PhD STUDENTS:
Lukasz Roguski (until July), Andrea Dieguez (from September)

Summary

The Biomedical Genomics Group works on deepening the understanding of the function of the genome in relation to disease. We apply computational methods to determine genetic and genomic causes of disease and reversely also study the effects of the disease on the genome. For our studies we use data that is generated at the CNAG and combine it with data that we retrieve from other sources. This allows us to increase the power of our studies and ask the data questions that were not necessarily at the base of the initial study design. Combining multiple different levels of omics data such as genomics, epigenomics, transcriptomics, proteomics and metabolomics provides an additional layer from which to extract insights. However, techniques for multi-omic analysis still require the development of suitable analytical approaches. Our focus is on three classes of diseases: 1) Cancer, 2) Rare diseases, and 3) Respiratory disorders.

Research Projects

  • Cancer: Our main effort here continues to be on the ICGC-PanCancer study, where we have been investigating the origin of somatic mutations in cancer genomes and the reasons for somatic mutations to occur as the same place in different patients. We have been coordinating the Quality Control working group of the ICGC-PanCancer study and delivered a quality framework and assessment of the over 2700 cancer genomes of this study. Our downstream analysis of the somatic mutations in these 2700 cancer genomes has given some highly interesting insights into the relationship of certain types of mutations and the tissue of origin of a cancer, and pan-cancer classes of cancers, such a microsatellite instable or immunoglobulin hyper-mutating tumours.
  • Rare Disease: In rare diseases we have been concentrating on the RD-Connect project and data with the objective to mine the data for phenotype-specific modifier variants. We are also developing new tools to connect to the RD-Connect Genome-Phenome Analysis Platform. Particular focus is on the effect of rare disease causing genetic variants on protein changes and structural changes of the proteins in the context of their interacting partners.
  • Respiratory Disorders: In respiratory disorders we have been investigating the manifestation of genomic alterations and their relation to gene expression and clinical phenotypes with a particular focus on the presentation of early signs of known and potentially causal genomic events.

Selected Publications

Boycott KM, Rath A, Chong JX, Hartley T, Alkuraya FS, Baynam G, Brookes AJ, Brudno M, Carracedo A, den Dunnen JT, Dyke SOM, Estivill X, Goldblatt J, Gonthier C, Groft SC, Gut I, Hamosh A, Hieter P, Höhn S, Hurles ME, Kaufmann P, Knoppers BM, Krischer JP, Macek M Jr, Matthijs G, Olry A, Parker S, Paschall J, Philippakis AA, Rehm HL, Robinson PN, Sham PC, Stefanov R, Taruscio D, Unni D, Vanstone MR, Zhang F, Brunner H, Bamshad MJ, Lochmüller H.
“International Cooperation to Enable the Diagnosis of All Rare Genetic Diseases.”
Am J Hum Genet, 100(5):695-705 (2017).

Grey C, Clément JA, Buard J, Leblanc B, Gut I, Gut M, Duret L, de Massy B.
“In vivo binding of PRDM9 reveals interactions with noncanonical genomic sites.”
Genome Res, 27(4):580-590 (2017).

Xue S, Maluenda J, Marguet F, Shboul M, Quevarec L, Bonnard C, Ng AY, Tohari S, Tan TT, Kong MK, Monaghan KG, Cho MT, Siskind CE, Sampson JB, Rocha CT, Alkazaleh F, Gonzales M, Rigonnot L, Whalen S, Gut M, Gut I, Bucourt M, Venkatesh B, Laquerrière A, Reversade B, Melki J.
“Loss-of-Function Mutations in LGI4, a Secreted Ligand Involved in Schwann Cell Myelination, Are Responsible for Arthrogryposis Multiplex Congenita.”
Am J Hum Genet, 100(4):659-665 (2017).

Curiel-Olmo S, Mondéjar R, Almaraz C, Mollejo M, Cereceda L, Marès R, Derdak S, Campos-Martín Y, Batlle A, González de Villambrosía S, Gut M, Blanc J, Traverse-Glehen A, Verney A, Baseggio L, Camacho FI, Wotherspoon A, Stamatopoulos K, Xochelli A, Papadaki T, Kanellis G, Ponzoni M, García-Cosío M, Vaqué JP, Beltrán S, Gut I, Piris MA, Martínez N.
“Splenic diffuse red pulp small B-cell lymphoma displays increased expression of cyclin D3 and recurrent CCND3 mutations.”
Blood, 129(8):1042-1045 (2017).

Tost J, Gut IG.
“Molecular Techniques for DNA Methylation Studies, in Molecular Diagnostics (Third Edition).”
Elsevier, Edited by George P. Patrinos, Philip B. Danielson and Wilhelm J. Ansorge. ISBN: 978-0-12-802971-8 (2017).