| Autor: |
Xing Yi Woo, Anuj Srivastava, Joel H. Graber, Vinod Yadav, Vishal Kumar Sarsani, Al Simons, Glen Beane, Stephen Grubb, Guruprasad Ananda, Rangjiao Liu, Grace Stafford, Jeffrey H. Chuang, Susan D. Airhart, R. Krishna Murthy Karuturi, Joshy George, Carol J. Bult |
| Jazyk: |
angličtina |
| Rok vydání: |
2019 |
| Předmět: |
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| Zdroj: |
BMC Medical Genomics, Vol 12, Iss 1, Pp 1-19 (2019) |
| Druh dokumentu: |
article |
| ISSN: |
1755-8794 |
| DOI: |
10.1186/s12920-019-0551-2 |
| Popis: |
Abstract Background Patient-derived xenograft (PDX) models are in vivo models of human cancer that have been used for translational cancer research and therapy selection for individual patients. The Jackson Laboratory (JAX) PDX resource comprises 455 models originating from 34 different primary sites (as of 05/08/2019). The models undergo rigorous quality control and are genomically characterized to identify somatic mutations, copy number alterations, and transcriptional profiles. Bioinformatics workflows for analyzing genomic data obtained from human tumors engrafted in a mouse host (i.e., Patient-Derived Xenografts; PDXs) must address challenges such as discriminating between mouse and human sequence reads and accurately identifying somatic mutations and copy number alterations when paired non-tumor DNA from the patient is not available for comparison. Results We report here data analysis workflows and guidelines that address these challenges and achieve reliable identification of somatic mutations, copy number alterations, and transcriptomic profiles of tumors from PDX models that lack genomic data from paired non-tumor tissue for comparison. Our workflows incorporate commonly used software and public databases but are tailored to address the specific challenges of PDX genomics data analysis through parameter tuning and customized data filters and result in improved accuracy for the detection of somatic alterations in PDX models. We also report a gene expression-based classifier that can identify EBV-transformed tumors. We validated our analytical approaches using data simulations and demonstrated the overall concordance of the genomic properties of xenograft tumors with data from primary human tumors in The Cancer Genome Atlas (TCGA). Conclusions The analysis workflows that we have developed to accurately predict somatic profiles of tumors from PDX models that lack normal tissue for comparison enable the identification of the key oncogenic genomic and expression signatures to support model selection and/or biomarker development in therapeutic studies. A reference implementation of our analysis recommendations is available at https://github.com/TheJacksonLaboratory/PDX-Analysis-Workflows. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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