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• Transfer Learning Associates CAFs with EMT and Inflammation in Tumor Cells in Human Tumors and Organoid Co-Culture in Pancreatic Ductal Adenocarcinoma

  This study examined the transcriptional changes induced by cancer associated fibroblasts (CAFs) in pancreatic ductal adenocarcinoma patient-derived tumor organoids. We hypothesized that cancer associated fibroblasts impacted tumor cell transcription to promote tumorigenic behavior. Using patient-matched cells from 3 patients, we compared the transcriptional profiles of patient-derived organoids in monoculture to patient-derived organoids co-cultured with CAFs. Similarly, we looked at the transcriptional changes in matched patient-derived cancer associated fibroblasts grown in monoculture or co-cultured with patient-derived organoids. With a focus on intercellular crosstalk, we identified crosstalk between cancer associated fibroblasts and patient-derived organoids through VEGFA and NRP1. This was identified by bulk RNA sequencing and examined dynamically in organoid-CAF co-culture. This dbGaP deposit is the bulk RNA sequencing data for these 3 patients.

  Study phs003563

• Shotgun Transcriptome and Isothermal Profiling of SARS-CoV-2 Infection Reveals Unique Host Responses, Viral Diversification, and Drug Interactions

  In less than nine months, the Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) has killed hundreds of thousands of people, including >23,000 in New York City (NYC) alone. The pandemic's sudden emergence highlights the clinical need to detect infection, track strain evolution, and identify biomarkers of disease course. To address these challenges, we provide large-scale shotgun metatranscriptomics (total-RNA-seq) for host, viral, and microbial profiling. In version 1, we sequenced a total of 732 clinical specimens (nasopharyngeal (NP) swabs) gathered from 669 unique patients in New York City during the first two months of the outbreak. In version 2, we sequenced an additional 168 clinical specimens from autopsy tissues (lung, heart, kidney, liver, and lymph node) from 60 patients, yielding a broad molecular portrait of the emerging COVID-19 disease across 900 clinical specimens and 729 patients.

  Study phs002258

• NHLBI TOPMed: Stanford Cardiovascular Institute iPSC Biobank Study (SCVI)

  The proposed Stanford Cardiovascular Institute (SCVI) Biorepository will curate and manage an expanded collection of human induced pluripotent stem cell (iPSC) lines and provide investigators with iPSC materials generated using standardized protocols, with the overall objective of promoting the continued adoption and development of iPSC technology in cardiovascular research. Human iPSCs have revolutionized disease modeling, drug screening, and therapeutic research. However, it is also recognized that the need for specialized technical expertise and the associated cost have largely prevented individual research laboratories from adopting iPSC models in their inquiries, particularly in studies requiring multiple cell lines. To address this bottleneck, the proposed Biorepository will maintain our existing collection of iPSC lines and further expand the collection of iPSCs by recruiting 1,000 healthy, hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM) donors of both sexes and diverse racial/ethnic backgrounds (African Americans, Asians, Hispanics, and Whites).

  Study phs002338

• "Distinct immunometabolic signatures in circulating immune cells define disease outcome in acute-on-chronic liver failure"

  We performed single-cell transcriptomics of PBMC’s from healthy (n= 3), acute decompensated (AD) (n= 3) and Acute-on-chronic liver failure (ACLF) patients. Lay Summary: Acute-on-chronic liver failure (ACLF) develops in cirrhotic patients and is characterized by an hyper-inflammatory immune state driving multiple organ failure(s). As a paradox, circulating immune cells also show transcription and metabolic evidence of exhaustion, explaining why these patients are often susceptible to secondary infections. We characterized at a transcriptional level all circulating immune cells of ACLF patiens, and specifically unraveled a distinct recovery and non-recovery ACLF signature within the monocyte population. Moreover, these changes were closely linked to metabolic differences within these cells. The described alterations allowed for a robust prediction of recovery and non-recovery of patients at admission to the hospital.

  Study EGAS50000000391

• Beta-Blocker Evaluation in Survival Trial (BEST-BioLINCC)

  Data Access NOTE: Please refer to the “Authorized Access” section below for information about how access to the data from this accession differs from many other dbGaP accessions. Objectives The Beta-Blocker Evaluation of Survival Trial was designed to determine whether bucindolol hydrochloride- a nonselective beta-adrenergic blocker and mild vasodilator- would reduce the rate of death from any cause among patients with advanced heart failure and to assess its effects in various subgroups defined by ethnic background and demographic criteria- specifically women and members of minority groups. Background Although beta-adrenergic-receptor antagonists reduce morbidity and Mortality in participants with mild-to-moderate chronic heart failure, their effort on survival in participants with more advanced heart failure is unknown. Participants There were 2,708 participants. Conclusions Bucindolol resulted in no significant overall survival benefit. (Krause-Steinrauf et al., 2001, PMID: 11386264).

  Study phs003730

• Is the Gut Important in Multiple Joint Osteoarthritis? A Multimodal Investigation in Humans and Pet Dogs

  The Gut Health in Multiple Joint Osteoarthritis (MJOA) Study leverages data from parallel community-based cohorts in humans and in pet dogs to elucidate the role of altered microbiota in MJOA. One hundred Johnston County Health Study human participants were 35 to 70 years of age at enrollment (2022-2023), self-identified as Hispanic, White, or Black, and lived in Johnston County, North Carolina. Demographic, clinical information, multiple joint radiographs, and stool samples for microbiome profiling by 16S rRNA gene sequencing were obtained from all participants. Similar data were collected from an independent group of pet dogs (N=115) from the local community, at the North Carolina State University (NCSU) College of Veterinary Medicine. The central hypothesis of the study is that intestinal permeability, with or without dysbiosis, is a major driver in the development and worsening of MJOA.

  Study phs003980

• Identification and characterization of tertiary lymphoid structures in brain metastases

  Brain metastases (BrM) are the most common cancers in the brain. We performed transcriptome-wide gene expression profiling combined with spatial immune cell profiling to characterize the tumor immune microenvironment in BrM from different primary tumors. We found that BrM from lung carcinoma and malignant melanoma showed overall higher immune cell infiltration as compared to BrM from breast carcinoma. RNA sequencing-based immune cell deconvolution revealed gene expression signatures indicative of tertiary lymphoid structures (TLS) in subsets of BrM from lung cancer and melanoma. This finding was corroborated by multiplex immunofluorescence staining of immune cells in BrM tissue sections. Detection of TLS signatures was associated with prolonged survival after BrM diagnosis in lung cancer patients. Our findings highlight the cellular diversity of the tumor immune microenvironment in BrM of different cancer types and suggest a role of TLS formation for BrM patient outcome.

  Study EGAS50000000563

• Longitudinal single-cell transcriptomic study in patient-derived xenografts of pediatric T-ALL

  In this study, we conducted single cell full length total RNA sequencing (VASA-seq) on 13 matched pediatric T-ALL PDX samples at initial diagnosis and relapse, along with 5 non-relapsing PDX samples collected at initial diagnosis. We identified a subpopulation of T-ALL cells with stem-like cell features that expands substantially at relapse indicating resistance to first-line therapy. Chemotherapy resistance was further validated through functional testing: Two samples were subjected to in-vitro drug testing, treated with Cytarabine for three days, followed by single-cell transcriptomic analysis using 10x Genomics. Additionally, in-vivo drug testing was conducted on one sample, involving re-engraftment into mice and treatment with a combination of Vincristine, Doxorubicin, and Dexamethasone. Single-cell transcriptomic analysis using 10x Genomics was performed after 0, 15 and 30 days of treatment.

  Study EGAS50000000582

• High volume culture initiating in vitro evolution in neuroblastoma cell lines

  Despite the advent of advanced molecular prognostic tools, it is still difficult to predict the course of disease for cancer patients at the individual level. This lack of predictability is also reflected in many experimental cancer model systems, begging the question of whether certain biological aspects of cancer (eg. growth, evolution etc.) can ever be anticipated or if there remains an inherent unpredictability to cancer, similar to other complex biological systems. We demonstrate by a combination of agent-based mathematical modelling, analysis of patient-derived xenograft systems from multiple cancer types, and in-vitro culture that certain conditions may invoke chaotic fluctuations in the clonal landscape of cancer growth. Our findings indicate that under those conditions, the cancer genome may behave as a complex dynamic system, making its long-term evolution inherently unpredictable.

  Study EGAS00001007962

• RNA Ligation Precedes U6 snRNA/LINE-1 Retrotransposition

  Long Interspersed Element-1 (L1) retrotransposons make up approximately 17% of the human genome. L1 moves throughout the genome via a copy-and-paste mechanism termed retrotransposition. L1 retrotransposition also mobilizes other cellular RNAs such as SINES, U6 snRNA and, mRNA, which for the latter results in the formation of processed pseudogenes. In this study we demonstrate that the RNA ligase RtcB can create chimeric RNAs by joining U6 snRNAs to 5'-truncated L1 or other cellular RNAs. We also show that the retrotransposition of U6/L1 chimeric RNA leads to U6/L1 pseudogene formation. In sum, our data suggests that U6 snRNA and RtcB may have biological roles in addition to their essential functions in mRNA and tRNA splicing, and that the retrotransposition of chimeric RNAs could be a mechanism to create novel genes.

  Study phs001671