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• Pseudodiastrophic dysplasia exome sequencing dataset

  This dataset contains 7 paired end fastq files obtained with Illumina Hiseq and Nextseq sequencing of whole exomes relevant to a study of pseudodiastrophic dysplasia (PDD). It includes 3 patients from 2 unrelated families diagnosed with PDD, together with the four parents.

  Dataset EGAD00001005775

• Single cell RNAseq of PBMC from bladder cancer patients

  This dataset contains single cell RNA sequencing data of PBMC samples from 20 bladder cancer patients. cDNAs and single cell RNA libraries were prepared following manufacturer’s user guide (10x Genomics). Each library was sequenced in HiSeq4000 (Illumina) to achieve ~300 million reads following manufacturer’s sequencing specification.

  Dataset EGAD00001006182

• Single-Nuclei RNA-seq of healthy (post-mortem) and temporal lobe epilepsy (biopsy) subjects.

  To identify dysfunctional neuronal subtypes underlying seizure activity in the human brain, we have performed single-nucleus transcriptomics analysis of >110,000 neuronal transcriptomes derived from temporal cortex samples of multiple temporal lobe epilepsy and non-epileptic subjects.

  Dataset EGAD00001006575

• Single nucleus and in situ RNA sequencing reveals cell topographies in the human pancreas

  To investigate the cellular composition of the human pancreas, we performed single-nucleus sequencing from snap frozen biopsies of pancreata from adult, neonatal and diseased (chronic pancreatitis) human donors.

  Dataset EGAD00001006396

• 41 CRC Exome bam + 4 CRC paired fastq from EGAS00001002477 study

  This dataset contain 45 pairs of colorectal tumor and adjacent normal tissue. Four of them are from a previous study EGAS00001002477. For each sample a BAM was generated by aligning to GRCh37. Those colorectal cancer all have the MSI phenotype.

  Dataset EGAD00001006666

• PETAL Network: Outcomes Related to COVID-19 Treated With Hydroxychloroquine Among Inpatients With Symptomatic Disease (ORCHID) Trial

  ORCHID was a multicenter, blinded, placebo-controlled randomized trial conducted at 34 hospitals in the US between April 2 and June 19, 2020. Adults hospitalized with respiratory symptoms from severe acute respiratory syndrome coronavirus 2 infection were enrolled, with the last outcome assessment on July 17, 2020. The planned sample size was 510 patients with five interim analyses; however, the trial was stopped at the fourth interim analysis for futility with a sample size of 479 patients.The distribution of the day 14 clinical status score (measured using a 7-category ordinal scale) was not significantly different for patients randomized to receive hydroxychloroquine compared with placebo.Instructions for requesting individual-level data are available on BioData Catalyst at https://biodatacatalyst.nhlbi.nih.gov/resources/data/. Apply for data access in dbGaP. Upon approval, users may begin accessing requested data in BioData Catalyst. For questions about availability, you may contact the BioData Catalyst team at https://biodatacatalyst.nhlbi.nih.gov/contact.

  Study phs002299

• Molecular and Clinical Analyses of PHF6 Mutant Myeloid Neoplasia Provide Clues as to Their Pathogenesis and Therapeutic Targeting

  PHF6 mutations (PHF6MT) are identified in various myeloid neoplasms (MN). However, little is known about the precise function and consequences of PHF6 in MN. Our comprehensive genomic analyses yielded three main findings. Firstly, we revealed a different pattern of genes correlating with PHF6MT in male and female cases. When analyzing male and female cases separately, in only male cases, RUNX1 and U2AF1 were co-mutated with PHF6. In contrast, female cases revealed co-occurrence of ASXL1 mutations and X-chromosome deletions with PHF6MT. Next, proteomics analysis revealed a direct interaction between PHF6 and the pioneer transcription factor RUNX1. Both proteins co-localize in active enhancer regions that define the context of lineage differentiation. Finally, we demonstrated a negative prognostic role of PHF6MT, especially in association with RUNX1. The negative effects on survival were additive as PHF6MT cases with RUNX1 mutations had worse outcomes when compared to cases carrying single mutation or wild-type.

  Study phs003303

• Zostavax vaccination-induced changes in the T cell receptor repertoire to varicella zoster virus

  Diversity and size of the antigen-specific T cell receptor (TCR) repertoire are two critical determinants for successful control of chronic infection. Varicella zoster virus (VZV) that establishes latency during childhood is able to escape control mechanisms, in particular with increasing age. We examined the TCR diversity of VZV-specific CD4 T cells in individuals older than 50 years by studying three identical twin pairs and three unrelated individuals before and after vaccination with live attenuated VZV. While all individuals had a small number of dominant T cell clones, the breadth of the VZV-specific repertoire differed markedly among different individuals. A genetic influence was seen for the sharing of individual TCR sequences from antigen-specific cells, but not for repertoire richness or the selection of clonal dominance. VZV vaccination favored the expansion of infrequent VZV-specific TCRs including those from naïve T cells while leaving dominant T cell clones mostly unaffected.

  Study phs001082

• Integrative Somatic and Germline Computational Biology to Redefine Clinical Actionability in Solid Tumors

  Neuroendocrine tumors (NETs) are rare cancers that arise in the gastrointestinal tract and pancreas. The fundamental mechanisms driving gastroenteropancreatic NETs (GEP-NETs) growth remain incompletely elucidated; however, the heterogeneous clinical behavior of GEP-NETs suggests that both cellular lineage dynamics and tumor microenvironment influence tumor pathophysiology. Here, we performed single-cell RNA-sequencing (scRNA-seq) of fresh resections of GEP-NETs, including four pancreatic NETs, three small intestinal NETs, and one perigastric NET. We used single-cell sequencing to investigate the tumor and immune cellular landscapes of GEP-NET patients. Malignant GEP-NET gene and regulon expression was compared with normal, gastrointestinal endocrine cell differentiation and fate determination stages. We further characterized immune-immune and immune-tumor interaction networks within GEP-NETs, identifying novel therapeutic opportunities in the myeloid compartment of the microenvironment. Our findings highlight the transcriptomic heterogeneity that distinguishes the cellular landscapes of GEP-NET anatomic subtypes and reveal potential avenues for future precision medicine therapeutics.

  Study phs003141

• Delineation of the heterogeneous molecular landscape of HRS cells and their biological contributions to forming comprehensive TME ecosystems.

  The tissue architecture of classic Hodgkin Lymphoma (CHL) is unique among cancers and characterized by rare malignant Hodgkin and Reed-Sternberg cells that are co-evolving in a complex ecosystem of immune cells in the tumor microenvironment. The lack of a comprehensive systems-level interrogation has hindered the description of disease heterogeneity and clinically relevant molecular subtypes. Here, we employed an integrative, multimodal approach to characterize CHL tumors using malignant cell sequencing, spatial transcriptomics and imaging mass cytometry. We identified four molecular subtypes (CST, CN913, STB, and CN2P) each characterized by distinct clinical features, mutational patterns, malignant cell gene expression profiles, and spatial architecture of immune cell populations. Functional modeling of CSF2RB mutations, a characteristic feature of CST, revealed dysregulated oncogenic signaling and changes in tumor microenvironment crosstalk. These findings highlight the significance of multi-dimensional profiling in elucidating patterns of molecular alterations that drive immune ecosystems and underlie therapeutically exploitable vulnerabilities.

  Study EGAS00001008064