Motivation Controlling for tumor purity in molecular analyses is essential to allow for reliable genomic aberration calls, for inter-sample comparison and to monitor heterogeneity of cancer cell populations. In genome wide screening studies, the assessment of tumor purity is typically performed by means of computational methods that exploit somatic copy number aberrations. Results We present a strategy, called Purity Assessment from clonal MEthylation Sites (PAMES), which uses the methylation level of a few dozen, highly clonal, tumor type specific CpG sites to estimate the purity of tumor samples, without the need of a matched benign control. We trained and validated our method in more than 6000 samples from different datasets. Purity estimates by PAMES were highly concordant with other state-of-the-art tools and its evaluation in a cancer cell line dataset highlights its reliability to accurately estimate tumor admixtures. We extended the capability of PAMES to the analysis of CpG islands instead of the more platform-specific CpG sites and demonstrated its accuracy in a set of advanced tumors profiled by high throughput DNA methylation sequencing. These analyses show that PAMES is a valuable tool to assess the purity of tumor samples in the settings of clinical research and diagnostics. Availability and implementation https://github.com/cgplab/PAMES.

Tumor purity quantification by clonal DNA methylation signatures / Benelli, M.; Romagnoli, D.; Demichelis, F.. - In: BIOINFORMATICS. - ISSN 1367-4803. - 34:10(2018), pp. 1642-1649. [10.1093/bioinformatics/bty011]

Tumor purity quantification by clonal DNA methylation signatures

Benelli M.;Demichelis F.
2018-01-01

Abstract

Motivation Controlling for tumor purity in molecular analyses is essential to allow for reliable genomic aberration calls, for inter-sample comparison and to monitor heterogeneity of cancer cell populations. In genome wide screening studies, the assessment of tumor purity is typically performed by means of computational methods that exploit somatic copy number aberrations. Results We present a strategy, called Purity Assessment from clonal MEthylation Sites (PAMES), which uses the methylation level of a few dozen, highly clonal, tumor type specific CpG sites to estimate the purity of tumor samples, without the need of a matched benign control. We trained and validated our method in more than 6000 samples from different datasets. Purity estimates by PAMES were highly concordant with other state-of-the-art tools and its evaluation in a cancer cell line dataset highlights its reliability to accurately estimate tumor admixtures. We extended the capability of PAMES to the analysis of CpG islands instead of the more platform-specific CpG sites and demonstrated its accuracy in a set of advanced tumors profiled by high throughput DNA methylation sequencing. These analyses show that PAMES is a valuable tool to assess the purity of tumor samples in the settings of clinical research and diagnostics. Availability and implementation https://github.com/cgplab/PAMES.
2018
10
Benelli, M.; Romagnoli, D.; Demichelis, F.
Tumor purity quantification by clonal DNA methylation signatures / Benelli, M.; Romagnoli, D.; Demichelis, F.. - In: BIOINFORMATICS. - ISSN 1367-4803. - 34:10(2018), pp. 1642-1649. [10.1093/bioinformatics/bty011]
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11572/312475
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