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• The Gut Microbiome in Parkinson's Disease

  The uploaded data come from a nested case-control study, with participants with Premotor Parkinson Disease (PPS) as cases. In addition to the PPS cases, the study has three control groups: 1) constipation only controls, defined as those who only reported constipation, but not probable REM sleep behavior disorder (pRBD) or hyposmia; 2) healthy controls  who did not report constipation, pRBD or hyposmia; and 3) patients with recently diagnosed confirmed PD (diagnosed after January 1, 2010).  Participants were contacted between 2016 and 2020 for a set of two stool samples. All participants provided a baseline stool sample and a subset (N = 120) will provide a second stool sample.

  Study phs002193

• Metatranscriptomic Sequencing of Pulmonary Fluid in Immunocompromised Children

  Despite improved diagnostics, pulmonary pathogens in immunocompromised children frequently evade detection, leading to significant mortality. In version 1.0 of this study, we performed RNA-based next generation sequencing (mNGS) on 41 lower respiratory samples collected from 34 children. We identified a rich cross-domain pulmonary microbiome containing bacteria, fungi, RNA viruses, and DNA viruses in each patient. Potentially pathogenic bacteria were ubiquitous among samples but could be distinguished as possible causes of disease by parsing for outlier organisms. Potential pathogens were detected in half of samples previously negative by clinical diagnostics. In version 2.0, we included an addition 278 samples from 229 pediatric stem cell transplant patients with pulmonary disease.

  Study phs001684

• Single cell RNAseq 7 days - Calprotectin in vitro effects on human early hematopoiesis

  To explore the effects of calprotectin (CAL) on early hematopoiesis, we incubated CD34+ cells from four healthy donors for 7 days in the presence of stem cell factor (SCF), FLT3-ligand and thrombopoietin (TPO) without and with CAL, interleukin-6 (IL6) and the IL6_CAL combination before collecting cells. We performed the same experiment with CD34+ cells collected from three patients with JAK2-V617F-mediated myelofibrosis (MF). A total of 135,545 cells from healthy donors and 111,725 cells from myelofibrosis patients were analyzed by single-cell RNA sequencing (scRNA-seq) using the 10X Chromium droplet-based platform. Single cell RNAseq 7 days - Normal and tumor samples 4 conditons : -Control - Calprotectin - IL-6 - Calprotectin+IL-6

  Study EGAS50000000455

• Bulk ATACseq 7days - Calprotectin in vitro effects on human early hematopoiesis

  To explore the effects of calprotectin (CAL) on early hematopoiesis, we incubated CD34+ cells from four healthy donors for 7 days in the presence of stem cell factor (SCF), FLT3-ligand and thrombopoietin (TPO) without and with CAL, interleukin-6 (IL6) and the IL6_CAL combination before collecting cells. We performed the same experiment with CD34+ cells collected from three patients with JAK2-V617F-mediated myelofibrosis (MF). A total of 135,545 cells from healthy donors and 111,725 cells from myelofibrosis patients were analyzed by single-cell RNA sequencing (scRNA-seq) using the 10X Chromium droplet-based platform. Bulk ATACseq 7days - Normal and tumor samples 4 conditons : -Control - Calprotectin - IL-6 - Calprotectin+IL-6

  Study EGAS50000000456

• Re-evaluation of human mitochondrial DNA methylation reveals signals consistent with technical artifacts

  The existence and functional relevance of mitochondrial DNA (mtDNA) methylation remain controversial. We assessed 5mC and 5hmC in human brain, blood, and related cancers using both enzymatic and native DNA sequencing. While nuclear DNA exhibited expected methylation patterns, mtDNA consistently showed negligible methylation levels, indistinguishable from technical noise. Elevated methylation in nuclear-embedded mitochondrial sequences demonstrates a clear potential to confound mtDNA methylation measurements. Furthermore, technical discrepancies in mtDNA methylation were observed, underscoring the need for careful evaluation when interpreting data generated using earlier sequencing workflows. Our findings provide evidence against the presence of 5mC or 5hmC in mtDNA under the physiological and pathological conditions studied.

  Study EGAS50000001186

• Lessons learned from the exome sequencing of nine cases of infertility and the way forward

  This study investigated the role of exome sequencing in the diagnosis of male and female infertility. Nine unrelated cases referred between 2019 and 2024 were analysed using exome sequencing, with segregation confirmed by Sanger sequencing and functional assays for splicing variants. We identified nine causative variants in genes including TUBB8, PATL2, CCDC39, STAG3, KIAA0319, FBXO43, AGBL5/BBS7, PLCZ1, and HS6ST1, six of which were novel. The findings highlight diverse reproductive phenotypes such as oocyte maturation arrest, early embryonic arrest, spermatogenic failure, and syndromic infertility. This work demonstrates the value of combining genetic, functional, and clinical approaches to improve diagnostic yield and patient care in reproductive failure.

  Study EGAS50000001320

• Insights into BRCA1 and TP53 associated breast cancer development from integrated whole genome analysis of mouse model mammary tumors

  Germline mutations in BRCA1 are a leading cause of hereditary breast cancer. We generated Brca1;Trp53 double conditional knockout (CKO) and Trp53 single CKO mouse models, both with either one or two copies of Trp53 deleted by Cre. We used whole-genome sequencing and optical genome mapping to interrogate the genomes of the resulting mammary tumors. Our comprehensive genomic analyses show that the Brca1;Trp53-CKO tumors recapitulate major genomic features of the human BRCA1 breast samples indicative of conserved fundamental mutational processes. This study also provides new insights into the genetic mechanisms of tumor development with potential implications for the treatment of BRCA1 cancers.

  Study EGAS50000001402

• Genomic profiling of ovarian adult type granulosa cell tumors

  To investigate the genomic landscape of primary and recurrent ovarian adult type granulosa cell tumors, we first identified an exploratory cohort comprised of cryopreserved surgical biopsies from 24 patients (primary, n = 8; recurrent, n = 16) with 20 having matched normal tissue or peripheral blood samples. We performed whole exome sequencing (WES) on these tumor samples at 200X target coverage (mean 226; range 165-296) and also performed WES on the available normal samples. In addition, we performed cancer gene panel sequencing using the T200.1 hybrid capture platform on FFPE tissue from 55 additional patients (primary, n = 27; recurrent, n = 28), of which we sequenced matched normal tissue for a total of 44.

  Study EGAS00001002833

• Neoadjuvant chemotherapy alters the genomic landscape and immune microenvironment of breast cancers

  To characterize the effects of neoadjuvant chemotherapy (NAC) on the genome, transcriptome and tumor infiltrating leukocytes (TILs), we have conducted whole exome and whole transcriptome sequencing of a comprehensive, longitudinal breast cancer cohort consisting of 146 cases and 281 paired tumor samples. In total, 52 (38%) patients achieved pathologic complete response (pCR) while 85 patients (62%) had residual disease with standard chemotherapy regimen. Tumor biopsies were collected for each patient at three time points – pre-treatment, three weeks after the first cycle of anthracycline and cyclophosphamide (AC) and at the time of surgery after 3 more cycles of AC followed by 4 cycles of taxane or taxane plus Herceptin in case of HER2+ subtype.

  Study EGAS00001003354

• 10X whole single cell RNA-seq from pre-frontal cortex biopsy

  The biopsy procedure was performed by a standard operative procedure under general anaesthesia. The placement of burr hole on the frontal lobe, opening of dura and cortex was performed in a routine fashion for VP shunt or VCS surgery. The biopsy was sharp dissected with knife through the leptomeninges, forming a tissue block consisting of cortex and subcortex, and placed in a sterile tube containing CSF. Fresh tissue sample processing was performed within the hours after surgery. The tissue was dissociated followed by red cell and debris removal and counting of the cells to be sequenced with (scRNA-seq; 10x Genomics). After dissociation only non neuronal cells were retrieved.

  Study EGAS50000001058