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• Longitudinal analysis of bone marrow heterogeneity reveals the co-evolution of malignant B cells and their T-cell niche supporting follicular lymphoma persistence

  Follicular Lymphoma (FL) is an indolent lymphoid malignancy characterized by cycles of remission and relapse, reflecting the inability of current therapies to fully eradicate tumor cells. Our hypothesis is that rare cancer precursor/persister cells (CPCs) evade treatment by homing to a protective tumor microenvironment, particularly within the bone marrow (BM), and/or by adopting specific cellular states, and form a rare reservoir of residual cells seeding lymphoma recurrence. To adress this, we collected paired BM samples at diagnosis and one year post-therapy from a clinical trial (FLIRT trial, NCT02303119) and applied multi-modal single-cell analysis to dissect the transcriptomics determinants of rare drug-tolerant persister cells and their surrounding T-cell niche.

  Study EGAS50000001295

• NHLBI TOPMed: TReating Children to Prevent EXacerbations of Asthma (TREXA)

  TREXA is a 44-week randomized, double-blind, double-masked, four-treatment, parallel trial that will evaluate the weaning strategy that provides the best protection against the development of exacerbations in children whose asthma is acceptably controlled on a low dose of ICS (per NAEPP guidelines). Following the 4 weeks of the run-in period on a 1x dose of ICS (100 µg fluticasone b.i.d. or its equivalent), children who do not meet the definition of acceptable asthma control will be randomized to the parallel BADGER protocol; those who meet the definition of acceptable asthma control will be enrolled into the 44-week treatment phase of the study. The primary outcome measure will be time to first exacerbation requiring a prednisone course.

  Study phs001732

• Construction of endoscopic biopsy banking for understanding the intestinal environment in colorectal diseases and exploratory studies using these banking systems.

  Colorectal cancer is the most common type of cancer in Japan. Although some colorectal cancers have a genetic background, most colorectal cancers are sporadic. Known risk factors for colorectal cancer include smoking, obesity, lack of exercise, and red and processed meat. Furthermore, although it has been suggested that changes in the intestinal environment due to changes in diet and lifestyle may be involved in the increased incidence of colorectal cancer in Japan, the molecular mechanism has not yet been fully elucidated. The main objective of this study is to elucidate the changes in the intestinal environment that cause colorectal tumors, and also to contribute to the establishment of colorectal mucosal tissue banking in Japan.

  Study JGAS000655

• NMR metabolic biomarkers in Biobank Japan generated by Nightingale Health Japan

  The BioBank Japan (BBJ) is a biobank established in the Institute of Medical Science, the University of Tokyo to collect clinical information and biological materials (DNA and serum samples). It collected about 200 thousand participants of 47 diseases started in 2003 (BBJ 1st cohort), and 67 thousand participants of 38 diseases started in 2013 (BBJ 2nd cohort), both in collaboration with 12 medical centers through the MEXT and AMED's "The BioBank Japan Project." This project is aiming at further utilization of the materials, and clinical and genomic information managed by BBJ to contribute to precision medicine by storing, managing, and providing the materials and data, as well as identifying biomarkers associated with disease risk, prognosis, and drug sensitivity.

  Study JGAS000561

• CRISPR-screening identifies mechanisms of resistance to KRASG12C and SHP2 inhibitor combinations in non-small cell lung cancer

  Although KRASG12C inhibitors show clinical activity in patients with KRAS G12C mutated NSCLC and other solid tumor malignancies, response is limited by multiple mechanisms of resistance. The KRASG12C inhibitor JDQ443 shows enhanced preclinical antitumor activity combined with the SHP2 inhibitor TNO155, and the combination is currently under clinical evaluation. To identify rational combination strategies that could help overcome or prevent some types of resistance, we evaluated the duration of tumor responses to JDQ443 �� TNO155, alone or combined with the PI3K�� inhibitor alpelisib and/or the CDK4/6 inhibitor ribociclib, in xenograft models derived from a KRASG12C-mutant NSCLC line and investigated the genetic mechanisms associated with loss of response to combined KRASG12C/SHP2 inhibition.

  Study JGAS000643

• ICGC PanCancer Analysis of Whole Genomes

  The Pancancer Analysis of Whole Genomes (PCAWG) study is an international collaboration to identify common patterns of mutation in more than 2,800 cancer whole genomes from the International Cancer Genome Consortium. Building upon previous work which examined cancer coding regions (Cancer Genome Atlas Research Network, The Cancer Genome Atlas Pan-Cancer analysis project, Nat. Genet. 2013 45:1113), this project is exploring the nature and consequences of somatic and germline variations in both coding and non-coding regions, with specific emphasis on cis-regulatory sites, non-coding RNAs, and large-scale structural alterations.

  Study EGAS00001001692

• Mutational_landscape_in_haemochromatosis__WGS_

  Somatic mutation has recently been shown to play a role in disease other than cancer. Driver mutations associated with lipid metabolism and insulin pathway have been identified in non-alcoholic fatty liver disease (NAFLD). It is plausible that driver mutations seen in NAFLD are a consequence of selection pressure exerted on hepatocytes in the context of excess fat accumulation. It has not been investigated whether selection pressure and driver landscape varies between chronic liver diseases of different aetiologies. This study aims to investigate mutational landscape in haemochromatosis, which is a disorder caused by a build-up of iron in the liver. We aim to use data generated by whole-genome sequencing of laser-dissected microbiopsies from diseased livers to characterize driver landscape and mutational signatures in haemochromatosis patients.

  Study EGAS00001005157

• H3Africa - An integrated approach to the identification of genetic determinants of susceptibility to trypanosomiasis

  The over-arching aim of this network is to improve the health of people living in some of the poorest countries in the world that carry a disproportionate burden of infectious diseases. Despite their importance, the study of many tropical diseases has lagged behind that of diseases of developed countries. This network will redress the balance by performing high quality research into two neglected tropical diseases, human African Trypanosomiasis (HAT) and schistosomiasis. Our aim is to investigate the genetic determinants of the human reservoirs of HAT and schistosomiasis, filling an important knowledge gap, while extending and strengthening the underpinning infrastructure to deliver these scientific objectives in particular by developing the next generation of African geneticists.

  Study EGAS00001007173

• Comprehensive genetic analysis of uveal melanoma heterogeneity during metastatic progression

  Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. Despite improvement of diagnosis and treatment of the primary tumor, there is no effective treatment of metastatic disease and approximately half of patients will die within one year or less following metastases detection. Tumor heterogeneity has been proposed as a key factor of drug resistance. However, it has been scarcely studied in UM. The present project aims searching for specific drivers of the metastatic progression, describing the genomic and transcriptomic landscape of metastatic UM, exploring tumor heterogeneity and investigating its role in drug resistance. Thus whole exome sequencing and transcriptomics have been performed on constitutional, primary tumor and metastatic samples from 28 UM patients.

  Study EGAS00001002761

• Low_coverage_whole_genome_sequencing_of_samples_from_the__Cretan_Greek_isolate_collection_HELIC_MANOLIS

  Whole-genome sequencing at 1x of samples from the Cretan Greek isolate collection HELIC-MANOLIS. Genome-wide association studies of complex traits have been successful in identifying common variant associations, but a substantial heritability gap remains. The field of complex trait genetics is shifting towards the study of low frequency and rare variants, which are hypothesised to have larger effects. The study of these variants can be empowered by focusing on isolated populations, in which rare variants may have increased in frequency and linkage disequilibrium tends to be extended. This work focuses on an isolated population from Crete, Greece. Sequencing is very efficient in isolated populations, because variants found in a few samples will be shared by others in extended haplotype contexts, supporting accurate imputation.

  Study EGAS00001000392