PEIS: a novel approach of tumor purity estimation by identifying information sites through integrating signal based on DNA methylation data

Tumor purity plays an important role in understanding the pathogenic mechanism of tumors. The purity of tumor samples is highly sensitive to tumor heterogeneity. Due to Intratumoral heterogeneity of genetic and epigenetic data, it is suitable to study the purity of tumors. Among them, there are many purity estimation methods based on copy number variation, gene expression and other data, while few use DNA methylation data and often based on selected information sites. Consequently, how to choose methylation sites as information sites has an important influence on the purity estimation results. At present, the selection of information sites was often based on the differentially methylated sites that only consider the mean signal, without considering other possible signals and the strong correlation among adjacent sites. Considering integrating multi-signals and strong correlation among adjacent sites, we propose an approach, PEIS, to estimate the purity of tumor samples by selecting informative differential methylation sites. Application to 12 publicly available tumor datasets, it is shown that PEIS provides accurate results in the estimation of tumor purity which has a high consistency with other existing methods. Also, through comparing the results of different information sites selection methods in the evaluation of tumor purity, it shows the PEIS is superior to other methods. A new method to estimate the purity of tumor samples is proposed. This approach integrates multi-signals of the CpG sites and the correlation between the sites. Experimental analysis shows that this method is in good agreement with other existing methods for estimating tumor purity.

[1]  David Haussler,et al.  The UCSC genome browser and associated tools , 2012, Briefings Bioinform..

[2]  Xiaoqi Zheng,et al.  InfiniumPurify: An R package for estimating and accounting for tumor purity in cancer methylation research , 2018, Genes & diseases.

[3]  Han Xu,et al.  MethylPurify: tumor purity deconvolution and differential methylation detection from single tumor DNA methylomes , 2014, Genome Biology.

[4]  Michael Q. Zhang,et al.  FastDMA: An Infinium HumanMethylation450 Beadchip Analyzer , 2013, PloS one.

[5]  A. Perry,et al.  The emerging roles of DNA methylation in the clinical management of prostate cancer. , 2006, Endocrine-related cancer.

[6]  G. Getz,et al.  Inferring tumour purity and stromal and immune cell admixture from expression data , 2013, Nature Communications.

[7]  B. Tycko,et al.  Epigenetic gene silencing in cancer. , 2000, The Journal of clinical investigation.

[8]  Jun Wang,et al.  Predicting tumor purity from methylation microarray data , 2015, Bioinform..

[9]  A. Butte,et al.  Systematic pan-cancer analysis of tumour purity , 2015, Nature Communications.

[10]  Hilde van der Togt,et al.  Publisher's Note , 2003, J. Netw. Comput. Appl..

[11]  C. Perou,et al.  Allele-specific copy number analysis of tumors , 2010, Proceedings of the National Academy of Sciences.

[12]  Ya Wang,et al.  Accounting for differential variability in detecting differentially methylated regions , 2019, Briefings Bioinform..

[13]  Matteo Benelli,et al.  Tumor purity quantification by clonal DNA methylation signatures , 2018, Bioinform..

[14]  Dan Wang,et al.  IMA: an R package for high-throughput analysis of Illumina's 450K Infinium methylation data , 2012, Bioinform..

[15]  Lee E. Edsall,et al.  Human DNA methylomes at base resolution show widespread epigenomic differences , 2009, Nature.

[16]  Hao Wu,et al.  Estimating and accounting for tumor purity in the analysis of DNA methylation data from cancer studies , 2017, Genome Biology.

[17]  A. Feinberg,et al.  Increased methylation variation in epigenetic domains across cancer types , 2011, Nature Genetics.

[18]  R. Irizarry,et al.  Accounting for cellular heterogeneity is critical in epigenome-wide association studies , 2014, Genome Biology.

[19]  Z. Nie,et al.  The Association of Retinoic Acid Receptor Beta2(RARβ2) Methylation Status and Prostate Cancer Risk: A Systematic Review and Meta-Analysis , 2013, PloS one.

[20]  A. McKenna,et al.  Absolute quantification of somatic DNA alterations in human cancer , 2012, Nature Biotechnology.

[21]  Junliang Shang,et al.  Quantitative identification of differentially methylated loci based on relative entropy for matched case-control data. , 2013, Epigenomics.

[22]  Xiaoqi Zheng,et al.  Tumor purity and differential methylation in cancer epigenomics. , 2016, Briefings in functional genomics.

[23]  J. Rogers,et al.  DNA methylation profiling of human chromosomes 6, 20 and 22 , 2006, Nature Genetics.

[24]  Tamar Sofer,et al.  A-clustering: a novel method for the detection of co-regulated methylation regions, and regions associated with exposure , 2013, Bioinform..