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• Characterization of MCSP+ melanoma DCC and MelDCC lines

  To dissect the sequence of genotypic and phenotypic progression during early metastatic colonization, we searched for the earliest detectable disseminated cancer cells (DCC) and identified MCSP+ melanoma cells as strong candidates for metastasis founder cells (MFC) in lymph nodes. We isolated MCSP+ DCC from various stages of metastatic colony-formation, performed scRNA-seq and unravelled their phenotypic progression. Further we performed bulk sequencing on patient-derived DCC models (MelDCC) and showed that they exhibit an immunosuppressive activity on CD8 T cells.

  Study EGAS00001006702

• Altered enhancer-promoter interaction leads to MNX1 expression in pediatric acute myeloid leukemia with t(7;12)(q36;p13)

  Acute myeloid leukemia (AML) with the t(7;12)(q36;p13) translocation occurs only in very young children and has a poor clinical outcome. The expected oncofusion between breakpoint partners (MNX1 and ETV6) has only been reported in a subset of cases. However, a universal feature is the strong transcript and protein expression of MNX1, a homeobox transcription factor that is normally not expressed in hematopoietic cells. Here, we map the translocation breakpoints on chromosomes 7 and 12 in affected patients to a region proximal to MNX1 and either introns 1 or 2 of ETV6. The frequency of MNX1 overexpression in pediatric AML (n=1556, own and published data) is 2.4% and occurs predominantly in t(7;12)(q36;p13) AML. Chromatin interaction assays in a t(7;12)(q36;p13) iPSC cell line model unravel an enhancer-hijacking event that explains MNX1 overexpression in hematopoietic cells. Our data suggest that enhancer-hijacking is a more common and overlooked mechanism for structural rearrangement-mediated gene activation in AML.

  Study EGAS50000000130

• BLUEPRINT DNA methylation profiles of graft donors in allogenic hematopoietic stem cell transplantation

  Allogenic hematopoietic stem cell transplantation (HSCT) is a curative treatment for many hematological conditions. Acute graft-versus-host disease (aGVHD) is a prevalent immune-mediated complication following HSCT. Current diagnostic biomarkers that correlate with aGVHD severity, progression, and therapy response in graft recipients are insufficient. We investigated whether epigenetic marks measured in peripheral blood of healthy graft donors stratify aGVHD severity in HLA-matched sibling recipients prior to HSCT. We measured genome-wide DNA methylation levels in peripheral blood of 91 HSCT donors using Illumina Infinium HumanMethylation450 BeadChips. We showed that epigenetic signatures underlying aGVHD severity in recipients correspond to immune pathways relevant to aGVHD etiology. We identified distinct DNA methylation marks in graft donors that are associated with aGVHD severity status in recipients. Together, our findings suggest that ‘epigenetic matching’ of HSCT donor-recipient pairs in a clinical setting may be used in conjunction with genetic matching to inform both donor selection and transplantation strategy, with the ultimate aim of improving patient outcome.

  Study EGAS00001001287

• Combined Metabolic Activators Reduces Liver Fat in Nonalcoholic Fatty Liver Disease Patients

  Nonalcoholic fatty liver disease (NAFLD) refers to excess fat accumulation in the liver. In animal experiments and human kinetic study, we found that administration of combined metabolic activators (CMA) promotes the oxidation of fat, attenuates the resulting oxidative stress, activates mitochondria and eventually removes excess fat from the liver. Here, we tested the safety and efficacy of CMA in NAFLD patients in a placebo-controlled 10-week study. We found that CMA significantly decreased hepatic steatosis and levels of aspartate aminotransferase, alanine aminotransferase, uric acid, and creatinine, whereas found no differences on these variables in the placebo group after adjustment for weight loss. By integrating clinical data with plasma metabolomics and inflammatory proteomics as well as oral and gut metagenomics data, we revealed the underlying molecular mechanisms associated with the reduced hepatic fat and inflammation in NAFLD patients and identified the key players involved in the host-microbiome interactions. In conclusion, we showed that CMA can be used to develop a pharmacological treatment strategy in NAFLD patients.

  Study EGAS00001005616

• Exome Sequencing for Head and Neck Cancer Susceptibility

  This study seeks to find low frequency or rare genetic variants in genes carried by subjects from families with unexplained familial risk of head and neck cancer. Whole exome sequencing was used to identify genetic variation in head and neck cancer cases.

  Study phs002571

• Comprehensive survey for the construction of an integrated database of food, gut microbiome, and health information (the "Sukoyaka Health Survey")

  We conducted a cohort-based study to investigate the association between the genetic background and diet/lifestyle in 59 healthy Japanese. We analyzed some participants living in Nagasaki. Shotgun metagenomic sequencing of fecal microbiome were analyzed.

  Study JGAS000681

• Targeted sequencing data of regulatory regions in 200 Spanish ASD trios

  This dataset consists of genomic sequencing data obtained through targeted sequencing of regulatory regions ( 85,394 human cCREs from ENCODE v2, version 2, https://screenv2.wenglab.org/) in 200 ASD (Autism Spectrum Disorder) trios (father and mother unaffected and proband affected)(600 samples total). Sequencing was carried out at the Centre for Genomic Regulation (CRG), Barcelona, Spain. Uploaded files are .vcf (600 samples). The goals of our study were to detect de novo and inherited variants in ASD probands. Sequencing data were obtained in an Illumina NovaSeq6000 instrument.

  Dac EGAC50000000695

• ZFHX4 is necessary for dopaminergic neuron differentiation and controls cell cycle by regulating LIN28A

  ZFHX4 as a transcription factor specifically induced during the in vitro differentiation of iPSC-derived mDANs. Depletion of ZFHX4 during neuronal differentiation led to a significant reduction in the number of mDANs while its overexpression did not lead to any changes in mDAN count. Identification of ZFHX4 target genes using CUT&Tag profiling and RNA-seq upon ZFHX4 knock-down (KD) revealed its involvement in cell cycle regulation during mDAN differentiation

  Dataset EGAD50000001605

• Variant calling from CC220-MM-001 cohorts A,B,D

  These are genomic and transcriptomic high risk molecular segments for 167 samples collected at baseline from deidentified patients enrolled in cohorts A,B or D in the CC-220-MM-001 clinical study. Data are provided in a patient call table in csv format. Calls are generated from WGS data with mutations called by mutect2 best practices pipeline, CNV calls from Battenberg; and RNA-seq aligned with star aligner and quantified by Salmon.

  Dataset EGAD50000000388

• Processed RNA-seq data for clinical efficacy and biomarker analysis of neoadjuvant atezolizumab in operable urothelial carcinoma in the ABACUS trial

  ABACUS is a single arm phase 2 study that investigated 2 cycles of atezolizumab (1200mg Q3) prior to cystectomy in 95 patients with muscle invasive transitional cell cancer (T2-4N0M0). Pathological complete response (pCR) occurring in ≥20% of patients was the primary endpoint. Biomarker analysis on sequential tissue was a co-primary endpoint. This dataset includes the TPM and raw counts tables.

  Dataset EGAD00001006199