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• Assessment of genetic and epigenetic variation in human IPS cells

  In order to progress human induced pluripotent stem cells (hiPSCs) towards the clinic, several outstanding questions must be addressed. It is possible to reprogram different somatic cell types into hiPSCs but it is unlcear whether some cell types carry through fewer mutations through reprogramming (either due to mutations present in the primary cells, or mutations accumulated during reprogramming). Through in depth analysis of hiPSCs generated from different somatic cells, it will be possible to assess the variation in genetic stability of different cell types.

  Dataset EGAD00001000384

• Pharmacogenomic Evaluation of Antihypertensive Responses (PEAR and PEAR-2)

  The primary aim of the Pharmacogenomic Evaluation of Antihypertensive Responses grant (funded by NIH Pharmacogenomic Research Network grant U01 GM074492) was to identify genetic determinants of blood pressure response and adverse events after antihypertensive treatments. Two different clinical trials with genomic information available were included: PEAR-1 and PEAR-2 studies. The PEAR-1 study (clinicaltrials.gov identifier NCT00246519) was a randomized controlled clinical trial evaluating genetic determinants of BP responses and adverse metabolic responses to atenolol and hydrochlorothiazide (HCTZ) monotherapy and in combination (PMID: 19249413). Briefly, PEAR-1 recruited 768 hypertension individuals with uncomplicated hypertension who were randomized to either monotherapy of atenolol 50 mg daily or HCTZ 12.5 mg daily for 3 weeks, followed by dose titration to 100 mg and 25 mg daily, then the combination therapy. BP and metabolic responses to monotherapy and combination therapy were assessed after an average of 9 weeks of antihypertensive treatment. BP was measured using three different methods: home, office and ambulatory. For the BP analysis, a composite weighted average of the office, home, ambulatory daytime and nighttime BP responses was calculated based on the row sums of the inverse of the inter-method covariance matrices. Genomic DNA from PEAR-1 participants was genotyped using the Illumina Human Omni1MQuad BeadChip (Illumina, San Diego, CA, USA). The PEAR-2 study was a multicenter sequential monotherapy clinical trial (clinicaltrials.gov identifier NCT01203852) evaluating genetic determinants of BP response to metoprolol monotherapy and chlorthalidone monotherapy. After a washout period (if necessary), eligible hypertensive patients with uncomplicated hypertension received metoprolol tartrate 50 mg twice daily for 3 weeks and the dose was increased to 100 mg twice daily for an additional six weeks if an inadequate response was observed (>120/70 mm Hg and heart rate >55 beats/min). After second washout period, patients received chlorthalidone monotherapy. Home and office BP measurements were collected in PEAR-2 study. We have previously demonstrated that home BP is the more informative single BP measurement compared to the office BP measurement. Therefore, home BP is the phenotype used for the genome-wide association analysis for PEAR-2. PEAR-2 samples were genotyped using the Illumina Human Omni2.5S Beadchip (Illumina, San Diego, CA, USA).

  Study phs000649

• TIRE-seq_PDN

  TIRE-seq is a novel RNA sequencing method that integrates mRNA purification directly into library preparation, eliminating separate RNA extraction. The technique demonstrated utility across three biological applications, including capturing transcriptional changes in human T cells, identifying genes driving murine dendritic cell differentiation, and analyzing the dose-response effects of temozolomide on patient-derived neurospheres. With its simplified approach and high sequencing efficiency, TIRE-seq offers a cost-effective solution for large-scale gene expression studies.

  Dataset EGAD50000001261

• Anaplastic Thyroid Cancer aligned sequence data

  Sequence data in fastq format was aligned to the GRCH38 reference genome. Aligned sequence was preprocessed with GATK for Indel Realignment and Base Quality Score Recalibration. Duplicates were marked with Picard Mark Duplicates. Aligned sequence is in bam format. Details of the alignment can be found int he bam header. In total, data generated from 174 tumour samples 102 matched blood normal controls was aligned. Tumour samples were classified as Anaplastic Thyroid, Poorly-differentiated or well-differentiated cancers.

  Dataset EGAD00001004126

• Single cell RNA sequencing of colorectal cancer

  To understand intrinsic cancer cell signatures and the surrounding microenvironemt and their interactions, we performed single-cell RNA sequencing on 63,689 cells from 23 patients with 23 primary colorectal cancer and 10 matched normal mucosa samples. Analyzing of primary colorectal cancer and normal mucosa samples show a comprehensive cellular landscape of colon cancer, which is a valuable resource for the development of therapeutic strategies.

  Dataset EGAD00001005198

• WGS of off-target analysis of base editing in organoids

  Seven clonal organoid lines and one bulk wild-type control sample were paired-end whole-genome sequenced using the Illumina Novaseq 6000 system. We sequenced four clonal intestinal organoid lines harbouring engineered TP53 and FBXW7 mutations as well as three lines targeted for oncogenic APC/TP53/PIK3CA/SMAD4 mutations. The reads were mapped to hg38 genome assembly and data is provided as BAM files.

  Dataset EGAD00001009827

• snRNA sequencing of high-grade pancreatic neuroendocrine carcinoma (panNEC)

  High-grade pancreatic neuroendocrine carcinoma (panNEC) is a rare, aggressive cancer with limited tissue availability. Single-nucleus transcriptomics of five large-cell panNECs revealed two interesting neuroendocrine cell states: one highly proliferative with an aberrant brain-specific neuronal differentiation program and another stress-responsive state enriched for heat stress, hypoxia, and glycolysis. Our findings suggest potential therapeutic vulnerabilities, highlighting the need to evaluate the efficacy of combination therapies.

  Dataset EGAD00001016154

• International Genetics of Parkinson Disease Progression (IGPP) Consortium: EPIPARK and HBS2 Cohorts

  EPIPARK and HBS2 cohorts were analyzed as part of the International Genetics of Parkinson Disease Progression (IGPP) Consortium. EPIPARK is a population-based cohort to study non-motor symptoms in parkinsonism in the city of Lübeck, Germany led by Drs. Meike Kasten and Christine Klein. HBS2 is a recently enrolled subset of participants in the Harvard Biomarkers Study led by Dr. Clemens Scherzer (www.bwhparkinsoncenter.org/biobank) of 89 participants with a diagnosis of Parkinson Disease (PD). Genotyping with Illumina Infinium Multi-Ethnic Genotyping Arrays (MEGA chip) was performed by Dr. Scherzer, Harvard Medical School and Brigham and Women’s Hospital. 179 participants with a diagnosis of PD from EPIPARK and 89 participants with a diagnosis of PD from HBS2 met Q/C criteria were analyzed.

  Study phs002328

• Mucosal Melanoma Targeted Exome Sequencing Study (UCSF)

  Mucosal melanoma is a deadly disease that carries the worst prognosis amongst subtypes of melanoma. Like all melanomas, mucosal melanomas are frequently driven by activating mutations in the MAPK and/or PI3K pathways; however, unlike melanomas that arise on sun-exposed skin, mucosal melanomas harbor few point mutations. Instead, most somatic alterations involve structural alterations, which appear early during tumor progression. Molecular studies in mucosal melanoma generally only profile point mutations without interrogating copy number alterations, and pathogenic mutations are only found in 30% of cases. We sequenced 38 mucosal melanomas, and in addition to profiling point mutations, we looked for copy number alterations that amplify oncogenes or delete tumor suppressors.

  Study phs001594

• Amplicon sequencing of various tumors

  In our previous studies on advanced esophageal, gastric, and colorectal carcinomas, measurement of circulating tumor DNA (ctDNA) in terms of variant allele frequency (VAF) in blood suggested: (1) patients with high VAF have a high chance of relapse; (2) VAF changes in response to treatment; and (3) ctDNA VAF elevation precedes imaging diagnosis of relapse. It is thus necessary to investigate whether these findings can be generalized in a wide cancer spectrum, types of treatment, and relapse phenotypes across cancer types. In the present study, we conduct a non-interventional observational study in a wide cancer spectrum on the basis of technical establishment for ctDNA using our unique digital PCR probe library.

  Study JGAS000366