Rupp, Kevin and Loesch, Andreas and Hu, Yanren Linda and Nie, Chenxi and Schill, Rudolf and Klever, Maren and Pfahler, Simon and Grasedyck, Lars and Wettig, Tilo and Beerenwinkel, Niko and Spang, Rainer (2024) Modeling metastatic progression from cross-sectional cancer genomics data. BIOINFORMATICS, 40 (suppl1). i140-i150. ISSN 1367-4803, 1367-4811
Full text not available from this repository. (Request a copy)Abstract
Motivation Metastasis formation is a hallmark of cancer lethality. Yet, metastases are generally unobservable during their early stages of dissemination and spread to distant organs. Genomic datasets of matched primary tumors and metastases may offer insights into the underpinnings and the dynamics of metastasis formation.Results We present metMHN, a cancer progression model designed to deduce the joint progression of primary tumors and metastases using cross-sectional cancer genomics data. The model elucidates the statistical dependencies among genomic events, the formation of metastasis, and the clinical emergence of both primary tumors and their metastatic counterparts. metMHN enables the chronological reconstruction of mutational sequences and facilitates estimation of the timing of metastatic seeding. In a study of nearly 5000 lung adenocarcinomas, metMHN pinpointed TP53 and EGFR as mediators of metastasis formation. Furthermore, the study revealed that post-seeding adaptation is predominantly influenced by frequent copy number alterations.Availability and implementation All datasets and code are available on GitHub at https://github.com/cbg-ethz/metMHN.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | EVOLUTION; P53; cancer progression models; Mutual Hazard Networks; Markov chains; metastasis; cancer genomics; lung cancer |
| Subjects: | 000 Computer science, information & general works > 004 Computer science 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Institut für Funktionelle Genomik > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Informatics and Data Science > Department Computational Life Science > Lehrstuhl für Statistische Bioinformatik (Prof. Spang) Physics > Institute of Theroretical Physics > Chair Professor Braun > Group Tilo Wettig |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 26 Nov 2025 08:59 |
| Last Modified: | 26 Nov 2025 08:59 |
| URI: | https://pred.uni-regensburg.de/id/eprint/64312 |
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