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• The transcriptome and DNA methylome profiling of the early human post-implantation embryos

  whole genome sequencing data of parent blood samples. Single cell full-length RNA-seq and PBAT-Seq data of in vitro culture D6 to D14 human embryo.

  Dataset EGAD00001005137

• Small molecule screen reveals synergy of cell cycle checkpoint kinase inhibitors with DNA-damaging chemotherapies in medulloblastoma (methylation dataset)

  human medulloblastoma xenograft isolated from mouse brain was frozen and genomic DNA or RNA was extracted. Bisulfite converted DNA was processed and hybridised to illumina EPIC or 450K arrays using standard protocols. RNAseq was performed on total RNA.

  Dataset EGAD00001006583

• Cold Ischemia Study Dataset

  A total of 54 samples derived from 9 patients and frozem in 6 timepoints (T0 - immediately after resection, T1 - 10 minutes after resection, T2 - 20 minutes after resection, T3 - 30 minutes after resection, T4 - 45 minutes after resection, T5 - 60 minutes after resection) to assess the impact of ischemia on gene expression.

  Dataset EGAD00001015661

• Papuan Y chromosome Diversity Panel

  Island Southeast Asia and Oceania host one of the world’s richest assemblages of human phenotypic, linguistic and cultural diversity. Despite this, the region’s male genetic lineages are globally among the last to remain unresolved. We compiled ~9.7 Mb of Y chromosome sequence from a diverse sample of over 380 men from this region, including 152 first reported here. The granularity of this dataset allows us to fully resolve and date the regional Y chromosome phylogeny. This new high-resolution tree confirms two main population bursts: multiple rapid diversifications following the region’s initial settlement ~50 kya, and extensive expansions <6 kya. Notably, ~40-25 kya the deep rooting local lineages of C-M130, M-P256, and S-B254 show almost no further branching events in Island Southeast Asia, New Guinea and Australia, matching a similar pause in diversification seen in maternal mitochondrial DNA lineages. The main local lineages start diversifying ~25 kya, at the time of the Last Glacial Maximum. This improved Y chromosome topology highlights localized events with important historical implications, including pre-Holocene contact between Mainland and Island Southeast Asia, potential interactions between Australia and the Papuan world, and a sustained period of diversification following the flooding of the ancient Sunda and Sahul continents as the insular landscape observed today formed. The high-resolution phylogeny of the Y chromosome presented here thus enables a detailed exploration of

  Study EGAS00001006025

• Glioblastoma epigenome profiling identifies SOX10 as a master regulator of molecular tumour subtype

  Glioblastoma in adult patients are classified into four subtypes, IDH, MES, RTK I, and RTK II, based on DNA methylation and RNA expression data. Tumour subtype transitions commonly occur during the treatment of glioblastoma patients, and transitions to the mesenchymal (MES) subtype have been associated with therapy resistance and adverse prognosis. Here, we generate DNA methylome and histone modification data of glioblastoma primary tumours and show that glioblastoma subtypes differ by their enhancer landscapes. Using Core Regulatory Circuitry analysis of H3K27ac data, and independent analysis of RNA-derived gene regulatory networks, we identified 38 subtype master regulators whose cell type-specific activities we mapped in single-cell RNA sequencing data. These analyses identified the chromatin modifier SRY-Box 10 (SOX10) as a master regulator in tumours of the RTK I subtype. In functional studies we demonstrate that SOX10 loss causes a transition of RTK I tumour cells to a mesenchymal cellular state by altering the accessibility of enhancer-rich chromatin regions and their occupancy by Bromodomain Containing 4 (BRD4), a dynamic constituent of super-enhancers. Treatment with the BRD4 inhibitor JQ1 blocked this transition. These data demonstrate the fundamental role of enhancer chromatin remodelling and master regulator activity in the establishment, maintenance and plasticity of glioblastoma cellular states. We also make our data publically browsable at https://dkfz-b060.github.io/gb_browse/

  Study EGAS00001003953

• SG Peranakan Project: Genetic admixture in the culturally unique Peranakan Chinese population in Southeast Asia

  The Peranakan Chinese are culturally unique descendants of immigrants from China who settled in the Malay Archipelago ~300-500 years ago. Today, among large communities in Southeast Asia, the Peranakans have preserved Chinese traditions with strong influence from the local indigenous Malays. Yet, whether or to what extent genetic admixture co-occurred with the cultural mixture has been a topic of ongoing debate. We performed whole-genome sequencing (WGS) on 177 Singapore (SG) Peranakans and analyzed the data jointly with WGS data of Asian and European populations. We estimated that Peranakan Chinese inherited ~5.62% (95% confidence interval [CI]: 4.75-6.46%) Malay ancestry, much higher than that in SG Chinese (1.08%, 0.69-1.53%), southern Chinese (0.86%, 0.57-1.31%), and northern Chinese (0.25%, 0.18-0.33%). A sex-biased admixture history, in which the Malay ancestry was contributed primarily by females, was supported by X chromosomal variants, and mitochondrial (MT) and Y haplogroups. Finally, we identified an ancient admixture event shared by Peranakan Chinese and SG Chinese ~1,612 (95% CI: 1,345-1,923) years ago, coinciding with the settlement history of Han Chinese in southern China, apart from the recent admixture event with Malays unique to Peranakan Chinese ~190 (159-213) years ago. These findings greatly advance our understanding of the dispersal history of Chinese and their interaction with indigenous populations in Southeast Asia.

  Study EGAS00001005379

• Next-generation molecular analysis of surgical margins in oral squamous cell carcinoma for assessment of microscopic residual disease and personalized postoperative treatment decision

  Background : Patients operated for an early oral squamous cell carcinoma (OSCC) with clear margins have a 5-year local relapse rate of around 15%. Assessing the microscopic residual disease (MRD) remains a challenge. In a phase II prospective trial, we evaluated the tetranucleotide microsatellite instability markers in the surgical margins in T1-T2 OSCC resected with pathologically clear margins. Goal : Detect MRD in surgical margins and adapt the postoperative decision-making Details : Whole exome sequencing (WES) on early oral squamous cell carcinoma (OSCC) with clear margins, and on resection margins, 86 patients with a median follow-up of 58 months (range 30.4-83 months)

  Study EGAS50000000823

• EGAD00010000768

  Replication data for HipSci normal samples using both HumanCoreExome-12_v1 and HumanOmni2.5-8 BeadChips

  Dataset EGAD00010000768

• FASTQ NGS dataset for EGAS00001001632:New Brain Tumor Entities Emerge from Molecular Classification of CNS-PNETs

  Dataset EGAD00001001927

• iPSC variation file (VCF) for EBiSC

  EBiSC Whole Genome Sequencing processed VCF including VEP consequences

  Dataset EGAD00001003934