Project description:Low-coverage whole genome sequencing data for 30 PDOX models (28 early passages, 4 late passages (2 overlaps)), 3 cell lines, and 21 matching human tumors
Project description:Whole exome sequencing data to 30 PDOX models (28 early passages, 3 late passages (1 overlap)), 3 cell lines, and 20 matching human tumors
Project description:Single-cell RNA-sequencing was performed on the tumor microenvironment of the glioblastomas isolated from PDOX models (Golebiewska et al., Acta Neuropathologica, 2020; Oudin et al., STAR Protocols 2021). Sample names correspond to PDOX models. Normal mouse brain was used as a contol. One PDOX model was treated with temolozomide (P3TMZ).
Project description:We establish that subtelomeric regions together with some other functional elements like transposons are consistently under-replicated in metaphase.
Project description:Purpose: Next-generation sequencing (NGS) has revolutionized systems-based analysis of cellular pathways. The goals of this study are to compare the epigenomes of different patient-derived models of colorectal cancer (PDO, PDX and PDOX) to the original patient tumor. Methods: The Omni-ATAC protocol was utilized for ATAC library preparations. The nulcei were extracted from samples (PT, PDO, PDX and PDOX). For each sample set, three biological replicates were included. The libraries were sequenced using Illumina HiSeq 4000 PE 150bp. Results: Using an optimized data analysis workflow, we achieved high quality ATAC-seq library. Data were mapped to hg19 with over 90% mapping rate, and relative low mitochondria fraction (<30%). We used Diffbind to assess the chromatin accessibility enrichment in each model with a strict threshold of p <0.05 and |logFC|>1. Conclusions: Our study represents the first detailed analysis of CRC PDMC epigenome. CRC cells from all three models share chromatin alterations when compared to PT cells, representing a PT-PDMC epigenetic axis. Chromatin alterations in CRC cells are more similar betweeen PDOX and PDX than between PDOX and PDO, indicating that the growth environment of the model exerts strong influence on chraomtin adaptation in tumor cells.
Project description:A patient derived orthotopic xenograft (PDOX) was generated from a patient with an aggressive EMM to study in-depth genetic and epigenetic events and drug responses related to extramedullary disease. One of these studies was the evaluation of genetic imbalances by Affymetrix Cytoscan 750K array. The PDOX was derived from a fresh punch of an extramedullary cutaneous lesion that was orthotopically implanted in a NSG mouse. The PDOX mimicked histologic and phenotypic features of patient’s tumor. Cytogenetic studies revealed a hyperploid genome with multiple genetic poor-prognosis alterations. Copy number alterations were detected in all chromosomes.
Project description:The Library of Integrated Cellular Signatures (LINCS) is an NIH program which funds the generation of perturbational profiles across multiple cell and perturbation types, as well as read-outs, at a massive scale. The LINCS Center for Transcriptomics at the Broad Institute uses the L1000 high-throughput gene-expression assay to build a Connectivity Map which seeks to enable the discovery of functional connections between drugs, genes and diseases through analysis of patterns induced by common gene-expression changes. These files represent L1000 data generated during the LINCS Pilot Phase (2012-2015), as well as profiles generated for more specific purposes, such as assay development and validation projects or testing custom compounds or non-standard cell lines (not part of the core LINCS cell lines). Note: Related GEO projects include (a) Additional L1000 and RNA-Seq data used to validate the assay and improve the inference model, available at GSE92743 (b) The LINCS “production phase” (also termed Phase II, 2015-2020) which is generating an additional cohort of L1000 data, available at GSE70138. The Platform is GPL20573: Broad Institute Human L1000 epsilon https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GPL20573 For questions or assistance with this dataset, please email the CMap support team at: clue@broadinstitute.org