H2020Индивидуална стипендия2021–2023

SCEPTRE · Single Cell EPigenomic, Transcriptomic, and structural Rearrangement profiling to investigate Evolution in prostate cancer

„Хоризонт 2020“ — Действия „Мария Склодовска-Кюри“

Период: 2021-04-10 → 2023-04-09
Финансиране от ЕС: 174 806 €
Участници: 1
Схема: MSCA-IF

Линиите свързват координатора с партньорите.

Накратко на български

Ракът на простатата се анализира чрез промени в активността на гените (метилиране) и разликата между първичните тумори и метастазите. Това помага за по-точна диагностика и избор на подходящо лечение според конкретния подтип на заболяването.

Този кратък обзор е генериран от изкуствен интелект

Кратко обяснение, генерирано от езиков модел по текста на CORDIS. Оригиналът е по-долу.

Резултати накратко

Single Cell EPigenomic, Transcriptomic, and structural Rearrangement profiling to investigate Evolution in prostate cancer

Prostate cancer is the most commonly diagnosed cancer in men in the European Union, with a significant global impact. However, treating Prostate cancer is challenging due to its diverse nature. Different types of Prostate cancer exhibit distinct molecular and clinical characteristics, making it crucial to target treatments effectively. While recent research has shed light on genetic and transcriptomic variations, the role of epigenetics (changes in gene activity), such as DNA methylation, remains understudied. Understanding the epigenomic landscape of prostate cancer is vital for improving diagnosis and treatment outcomes. Current therapies may not be tailored to specific prostate cancer subtypes, leading to potential inefficacies and unnecessary side effects that not only affect patients' well-being but also incurs substantial healthcare costs. The SCEPTRE project focused on interdisciplinary research at the interface between artificial intelligence; genomic analysis, and translational research in prostate cancer. The overall objectives were: 1. Uncover DNA methylation alterations in prostate cancer: To elucidate DNA methylation variations in prostate cancer, we have analyzed an extensive dataset of prostate cancer cases, aiming to discern epigenetic discrepancies between primary tumors and metastatic sites. We aimed to ascertain their impact on gene expression and their pivotal role in tumor progression. 2. Uncover rare and diverse cell populations in prostate cancer: Developed and implemented state-of-the-art computational methodologies for the comprehensive analysis of individual cells within prostate tumors. This has enabled the thorough examination of rare and diverse cellular subpopulations, offering valuable insights into the cancer's origins and evolutionary trajectories. 3. Identification of novel genetic and epigenetic drivers in prostate cancer: Leverage cutting-edge long-read sequencing methods to facilitate the precise detection of concurrent genetic and epigenetic alterations, providing a deeper understanding of their contributions to tumor evolution.

Текст от CORDIS, на английски · Данни: CORDIS, © Европейски съюз

Цел на проекта

Prostate cancer (PrCa) is the most frequently diagnosed cancer in men in the European Union (EU), and is a molecularly and clinically heterogeneous disease. Although the genomic and transcriptomic landscapes of PrCa have been characterized deeply, the genome-wide epigenetic landscape and its contribution to tumor heterogeneity has received less attention. The lack of single-cell methylation (with parallel single-cell transcriptomic) datasets in solid tumors (and none in PrCA) has stunted inference on clonal evolution. Consequently, the understanding of the coordinated relationship between methylation and transcriptome remains tenuous at best. Structural variants have also not been able to be accurately resolved in cancer due to the reliance on short-read sequencing, and their interplay with DNA methylation is still poorly understood. I present the project, SCEPTRE which is tightly connected to and builds upon ample expertise in the laboratories of Prof. Christoph Plass, Division Chair of Cancer Epigenomics, DKFZ, and Dr. Oliver Stegle, Division Chair of Computational Genomics, DKFZ. Within this project, I will drive the generation of novel ‘single-cell’ and ‘single-molecule long-read’ PrCa datasets, and exploit existing data resources to comprehensively assess the epigenetic and joint transcriptomic and genomic dimensions of human PrCa with the aim to examine cancer evolution. To realize this aim, I will also derive a comprehensive computational toolbox for the analysis of single-cell (and single-molecule) DNA methylation and joint multi-omic profiles. This project will deliver novel innovative ways to identify epigenetic drivers; as well as link DNA methylation for lineage tracing as a biomarker for disease progression. Moreover, the project will uncover putative relationships between the DNA methylome and transcriptome as well as between structural genetic aberrations and epigenetic changes.

Оригинален текст от CORDIS (на английски).

Участници

DEUTSCHES KREBSFORSCHUNGSZENTRUM HEIDELBERG · HeidelbergКоординаторГермания