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• Data Access Committee for EGAS00001007299

  Dac EGAC00001003268

• DAC for noninvasive lung cancer subtyping

  Dac EGAC00001003474

• DAC for Molecular Oncology lab

  Dac EGAC50000000268

• DAC for EGAS00001007531

  Dac EGAC00001003437

• UCL Centre for Longitudinal Studies

  Dac EGAC00001003495

• DAC for v9 panel assay

  Dac EGAC00001003580

• Evaluation of Nuclear DNA from Rootless Hairs for Forensic Purposes

  The study aims to overcome current limitations in the recovery of DNA from small, difficult forensic samples. Particularly, our goal is to produce a robust laboratory protocol and the accompanying software to accelerate adoption, as well as to evaluate the reliability and robustness of both the laboratory and computational aspects of generating genotype files from minute and/or degraded DNA samples, such as single, rootless hairs.The data accompanying this study includes raw, paired-end reads from high-throughput sequencing of two panels of saliva, head hair, and pubic hair samples collected from anonymous volunteers at the University of California, Santa Cruz. The smaller set (Hair1.0) comprises 8 individuals, while the larger (Hair2.0) comprises 50 individuals, with 3 overlapping individuals between the two panels identified in post-collection analysis. We did not collect phenotype data or personally identifying information from the participants. For the Hair2.0 panel, only a subset of volunteers provided pubic hairs for DNA extraction and sequencing. Also included are saliva-derived genotype array data for all 8 individuals in the Hair1.0 panel and 44 of 50 individuals in the Hair2.0 panel.

  Study phs002979

• A Microwell Platform for High-Throughput Longitudinal Phenotyping and Selective Retrieval of Organoids

  In traditional bulk culture, organoids tend to overlap, hindering the analysis of individual organoid characteristics in a high-throughput manner. Additionally, variations in the local spatial properties of the bulk matrix make it challenging to distinguish whether phenotypic differences between organoids stem from inherent cellular disparities or disparities in the microenvironment. To address these challenges, we have developed a microwell-based technique that facilitates the quantification of image-based parameters for organoids grown from single cells. Furthermore, these organoids can be easily retrieved from their respective microwells for molecular profiling. By employing a deep-learning image processing pipeline, we conducted a comprehensive assessment of various phenotypic traits in two CRISPR-engineered human gastric organoid models. This analysis encompassed growth rates, cellular movement, and apical-basal polarity. Through our investigation, we successfully identified genomic alterations associated with increased growth rate, as well as changes in accessibility and expression patterns correlated with apical-basal polarity. This novel methodology offers a valuable tool for studying organoid behavior at a single-cell level, enabling researchers to gain deeper insights into organoid biology and associated genetic modifications.

  Study phs003315

• Genetic Underpinnings of Ethnic Disparities in Bone Toxicities Between Hispanic and Non-Hispanic Children Treated for Acute Lymphoblastic Leukemia

  Acute lymphoblastic leukemia (ALL) is the most common malignancy among children and young adolescents. More than 90% of children are cured with a combination of multiple chemotherapeutic drugs. Some may suffer from debilitating toxicities due to the cytotoxic drugs, necessitating pharmacogenetic research to search for genetic markers predictive of treatment toxicities, so that treatment can be better tailored based on patients' genetic makeup. Bone toxicities, including osteonecrosis and fractures, most often due to glucocorticoids, are the most common complications in ALL, which have long-lasting detrimental impact on the still developing skeletons in children. In DFCI ALL Consortium Protocol 05-001, a multi-center clinical trial for childhood ALL conducted in Canada and the US, we found that Hispanic children had less drug toxicities to their bones than non-Hispanic children. Although reasons for the observed ethnic differences are largely unknown, patients' inherited genetic background may be at play. This study seeks to perform a novel pharmacogenomic study based on multi-site clinical trials DFCI ALL Consortium Protocol 05-001 and 11-001 to identify genetic underpinnings of ethnic disparities in bone toxicities.

  Study phs002317

• DynaTag for efficient profiling of transcription factors in small samples and single cells

  Systematic discovery of transcription factor (TF) landscapes in low-input samples and at single cell level is a major challenge in the fields of molecular biology, genetics, and epigenetics. To address this, we present here cleavage under Dynamic targets and Tagmentation (DynaTag), which allows robust mapping of specific TF-DNA interactions via the use of a physiological salt solution during sample preparation. Using this method, we revealed occupancy alterations for 15 different TFs in stem cell and cancer tissue models. Of note, we showcased for NANOG, MYC, and OCT4 differentially occupied genomic loci during stem cell differentiation, both in bulk and at single-cell resolution. DynaTag demonstrated superior signal-to-background ratio and occupancy resolution in comparison to CUT&RUN and ChIP-seq. In addition, a model for small cell lung cancer chemotherapy treatment in vivo showed increased chromatin occupancies of the gain-of-function mutant P53 p.R248Q, FOXA1, and MYC at altered gene pathways, such as epithelial-mesenchymal-transition. Altogether, these results highlight the technical advancement of DynaTag to uncover TF landscapes in cell models and in tissues of a complex disease model.

  Study EGAS50000001074