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• Clinical data

  Clinical data from IMvigor210, POPLAR, IMmotion150: Clinical data include demographics, tumor type, PD-L1 IHC, tumor mutation burden, objective response rate, overall survival and progression free survival for 611 patients across IMvigor210, POPLAR and IMmotion150. Clinical data from PCD4989g: Clinical data include tumor type, PD-L1 expression and objective response rate for 206 patients from PCD4989g.

  Dataset EGAD00001006630

• Tumor detection by analysis of both symmetric- and hemi-methylation of plasma cell-free DNA

  Aberrant DNA methylation plays a critical role in tumorigenesis. While DNA methylation has been used for cancer detection and classification, DNA hemi-methylation, a novel epigenetic mark has not been analyzed extensively in cancer epigenomes. Here we report a strand-specific (ss) sequencing method (MeDIP-Seq) for plasma cell free (cf) DNA (sscf-MeDIP-Seq), which can analyze both symmetrically methylated DNA regions (DMRs) as well as hemi-methylated regions (DHMRs). Using the sscf-MeDIP-Seq method, we analyzed plasma cfDNA methylomes of 271 samples from subjects with liver cancer and brain cancer and from individuals without cancer (controls). Among them, 215 samples were chosen as the discovery cohort for the identification of DMRs and DHMRs specific in each subject group and for the training of machine learning models of multi-cancer detection (MCD) using DMRs, DHMRs and DMRs+DHMRs as inputs. These models were then used to predict the 56 samples in the validation cohort. We found that models trained with DMRs+DHMRs as inputs in general outperformed models trained with DMRs or DHMRs alone, with AUROC being 0.971, 0.981, and 0.99 in predicting control, liver and brain cancer samples in the validation cohort, respectively, by the DMR+DHMR-trained models.

  Study phs003462

• Copy number profiling of circulating cell-free DNA from high grade serous ovarian cancer patients

  Study EGAS00001004670

• ChIP-seq of plasma cell-free nucleosomes identifies gene expression programs of the cells-of-origin

  Cell-free DNA in human plasma provides access to molecular information about the pathological processes in the organs or tumors from which it originates. These DNA fragments are derived from fragmented chromatin in dying cells, and retain some of the cell of origin histone modifications. Here, we apply chromatin immunoprecipitation of cell-free nucleosomes carrying active chromatin modifications followed by sequencing (cfChIP-seq) to 268 human samples. In healthy donors, we identified bone marrow megakaryocytes, but not erythroblasts, as major contributors to the cfDNA pool. In patients with a range of liver diseases, we show that we can identify pathology-related changes in hepatocyte transcriptional programs. In metastatic colorectal carcinoma patients, we detected clinically relevant, and patient-specific information, including transcriptionally active HER2 amplifications. Altogether, cfChIP-seq using low sequencing depth, provides systemic and genome-wide information, can inform diagnosis, and facilitate interrogation of physiological and pathological processes using blood samples.

  Study EGAS00001004913

• PCR-free HiSeqX whole genome sequence data on 120 samples with triplet repeat expansions (premutation and full expansions)

  Whole genome sequence (WGS) data was generated on 120 Coriell samples with the following validated repeat expansions: Fragile X Syndrome, Huntington disease, Friedreich’s ataxia, Amyotrophic Lateral Sclerosis, Myotonic Dystrophy, Spinocerebellar Ataxia 1/3 and Dentatorubral-Pallidoluysian Atrophy. These samples were sequenced using 2x150bp reads on an Illumina HiSeqX sequencer and the repeat expansions were called using ExpansionHunter to demonstrate the ability to call large repeats from high throughput, PCR-free WGS data.

  Study EGAS00001002462

• single cell RNA-seq of peripheral blood from analysis in infants with MLL-rearranged Acute Lymphoblastic Leukemia

  This dataset contains two experiments. 1) Single cell RNA-seq of peripheral blood diagnostic samples from patients with MLL-rearranged infant ALL that underwent relapse or not (samples ending in R relapsed, samples ending in N did not), sequenced with SORT-seq (see cell systems, 2016, doi:10.1016/j.cels.2016.09.002). For some of the patients, multiple indipendent plates were produced (each plate is a sample). Barcode-well correspondence can be found here: https://bitbucket.org/princessmaximacenter/sharq/src/master/data/celseq2_bc384-v4.csv . 2) Single cell RNA-seq of peripheral blood diagnostic samples from patients with MLL-rearranged infant ALL that underwent relapse or not (samples ending in R relapsed, samples ending in N did not), sequenced with10x Genomics Version 2.

  Dataset EGAD00001007752

• Metabolic reprogramming towards OXPHOS identifies a novel therapeutic target for mantle cell lymphoma

  Metabolic reprogramming is linked to cancer cell growth and proliferation, metastasis, and therapeutic resistance in a multitude of cancers. Targeting dysregulated metabolic pathways to overcome resistance, an urgent clinical need in all relapsed/refractory cancers, remains difficult. Through genomics analysis of clinical specimens, we show that metabolic reprogramming towards oxidative phosphorylation (OXPHOS) and glutaminolysis is associated with therapeutic resistance to the Bruton’s tyrosine kinase inhibitor ibrutinib in mantle cell lymphoma (MCL), an incurable B-cell lymphoma with poor clinical outcomes. Inhibition of OXPHOS with a novel, clinically applicable small molecule, IACS-010759, which targets complex I of the mitochondrial electron transport chain, results in significant growth inhibition in vitro and in vivo in ibrutinib-resistant patient-derived cancer models. This work suggests that targeting metabolic pathways to subvert therapeutic resistance is a clinically viable approach to treat highly refractory malignancies.

  Dataset EGAD00001004577

• Transrenal DNA Analysis

  Urinary cell-free DNA (ucfDNA) is an emerging marker in liquid biopsy. However, the characteristics of transrenal DNA and urinary-tract DNA are not fully understood. Therefore, we investigated the fragmentomic features and demonstrated the potential clinical utilities of ucfDNA in the current study.

  Study EGAS50000000766

• End structure of DNA in plasma: detection, characterizationand diagnostic applications

  The physical properties of cell-free DNA fragments in plasma, such as fragment sizes and ends, have attracted much recent interest, leading to the emerging field of fragmentomics. This study attempted to further characterize the end structure of plasma DNA.

  Study EGAS00001004080

• Frequent mutation of the FOXA1 untranslated region in prostate cancer

  We sequenced the coding and untranslated regions of 72 prostate cancer driver genes in 712 plasma cell free DNA samples from 428 men with metastatic prostate cancer, in an effort to understand the role of untranslated region mutations in late stage prostate cancer.

  Study EGAS00001003113