Project description:<p>Improvement of variant calling in next-generation sequence data requires a comprehensive, genome-wide catalogue of high-confidence variants called in a set of genomes for use as a benchmark. We generated deep, whole-genome sequence data of seventeen individuals in a three-generation pedigree and called variants in each genome using a range of currently available algorithms. We used haplotype transmission information to create a phased "platinum" variant catalogue of 4.7 million single nucleotide variants (SNVs) plus 0.7 million small (1-50bp) insertions and deletions (indels) that are consistent with the pattern of inheritance in the parents and eleven children of this pedigree. Platinum genotypes are highly concordant with the current catalogue of the National Institute of Standards and Technology for both SNVs (>99.99%) and indels (99.92%), and add a validated truth catalogue that has 26% more SNVs and 45% more indels. Analysis of 334,652 SNVs that were consistent between informatics pipelines yet inconsistent with haplotype transmission ("non-platinum") revealed that the majority of these variants are <i>de novo</i> and cell-line mutations or reside within previously unidentified duplications and deletions. The reference materials from this study are a resource for objective assessment of the accuracy of variant calls throughout genomes.</p>
Project description:Resistance to platinum-based chemotherapy is a clinical challenge in the treatment of ovarian cancer (OC) and limits survival. Therefore, innovative drugs against platinum-resistance are urgently needed. Our therapeutic concept is based on the conjugation of two chemotherapeutic compounds to a monotherapeutic pro-drug, which is taken up by cancer cells and cleaved into active cytostatic metabolites. Here, we explore the activity of the duplex-prodrug 5-FdU-ECyd, covalently linking 2'-deoxy-5-fluorouridine (5-FdU) and 3'-C-ethynylcytidine (ECyd), on platinum-resistant OC cells. RNA-Sequencing was used for characterization of 5-FdU-ECyd treated platinum-sensitive A2780 and isogenic platinum-resistant A2780cis.
Project description:Ovarian cancer is one of the leading causes of death in females in the world. High-grade serous ovarian carcinoma (HGSOC) is the most common histological subtype, and the platinum-resistance is a clinical challenge, In this study, we investigated the microRNA (miRNA) profiles of platinum-resistant and platinum-sensitive HGSOC.
Project description:In this study, 4D data-independent acquisition (DIA) proteomic sequencing was performed on exosomes obtained from 58 platinum-sensitive and 30 platinum-resistant patients with EOC. The analysis revealed a notable enrichment of differentially expressed proteins that were predominantly associated with immune-related pathways. Moreover, pivotal immune-related proteins (IRPs) were identified by LASSO regression. These factors, combined with clinical parameters selected through univariate logistic regression, were used for the construction of a model employing multivariate logistic regression.
Project description:Ovarian cancer is one of the leading causes of death in females in the world. High-grade serous ovarian carcinoma (HGSOC) is the most common histological subtype, and platinum platinum-resistance is a clinical challenge, In this study, we investigated the gene expression profiles of platinum-resistant and platinum-sensitive HGSOC.
Project description:ChIP-seq for H3K9me3 was performed in A2780 (platinum sensitive) and A2780cis (platinum resistant) cells and in sensitive A2780 cells with shRNA induced knockdown of FLYWCH1.
