Gbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressions
Abstract Background DNA methylation is a biochemical process in which a methyl group is added to the cytosine-phosphate-guanine (CpG) site on DNA molecules without altering the DNA sequence. Multiple CpG sites in a certain genome region can be differentially methylated across phenotypes. Identifying...
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| Format: | Article |
| Language: | English |
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BMC
2024-03-01
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| Series: | BMC Bioinformatics |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s12859-024-05711-y |
| _version_ | 1797273065920397312 |
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| author | Chengzhou Wu Xichen Mou Hongmei Zhang |
| author_facet | Chengzhou Wu Xichen Mou Hongmei Zhang |
| author_sort | Chengzhou Wu |
| collection | DOAJ |
| description | Abstract Background DNA methylation is a biochemical process in which a methyl group is added to the cytosine-phosphate-guanine (CpG) site on DNA molecules without altering the DNA sequence. Multiple CpG sites in a certain genome region can be differentially methylated across phenotypes. Identifying these differentially methylated CpG regions (DMRs) associated with the phenotypes contributes to disease prediction and precision medicine development. Results We propose a novel DMR detection algorithm, gbdmr. In contrast to existing methods under a linear regression framework, gbdmr assumes that DNA methylation levels follow a generalized beta distribution. We compare gbdmr to alternative approaches via simulations and real data analyses, including dmrff, a new DMR detection approach that shows promising performance among competitors, and the traditional EWAS that focuses on single CpG sites. Our simulations demonstrate that gbdmr is superior to the other two when the correlation between neighboring CpG sites is strong, while dmrff shows a higher power when the correlation is weak. We provide an explanation of these phenomena from a theoretical perspective. We further applied the three methods to multiple real DNA methylation datasets. One is from a birth cohort study undertaken on the Isle of Wight, United Kingdom, and the other two are from the Gene Expression Omnibus database repository. Overall, gbdmr identifies more DMR CpGs linked to phenotypes than dmrff, and the simulated results support the findings. Conclusions Gbdmr is an innovative method for detecting DMRs based on generalized beta regression. It demonstrated notable advantages over dmrff and traditional EWAS, particularly when adjacent CpGs exhibited moderate to strong correlations. Our real data analyses and simulated findings highlight the reliability of gbdmr as a robust DMR detection tool. The gbdmr approach is accessible and implemented by R on GitHub: https://github.com/chengzhouwu/gbdmr . |
| first_indexed | 2024-03-07T14:38:15Z |
| format | Article |
| id | doaj.art-d4158361311b4e2a91f018d2f270bd5c |
| institution | Directory Open Access Journal |
| issn | 1471-2105 |
| language | English |
| last_indexed | 2024-03-07T14:38:15Z |
| publishDate | 2024-03-01 |
| publisher | BMC |
| record_format | Article |
| series | BMC Bioinformatics |
| spelling | doaj.art-d4158361311b4e2a91f018d2f270bd5c2024-03-05T20:31:53ZengBMCBMC Bioinformatics1471-21052024-03-0125111710.1186/s12859-024-05711-yGbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressionsChengzhou Wu0Xichen Mou1Hongmei Zhang2School of Public Health, University of MemphisSchool of Public Health, University of MemphisSchool of Public Health, University of MemphisAbstract Background DNA methylation is a biochemical process in which a methyl group is added to the cytosine-phosphate-guanine (CpG) site on DNA molecules without altering the DNA sequence. Multiple CpG sites in a certain genome region can be differentially methylated across phenotypes. Identifying these differentially methylated CpG regions (DMRs) associated with the phenotypes contributes to disease prediction and precision medicine development. Results We propose a novel DMR detection algorithm, gbdmr. In contrast to existing methods under a linear regression framework, gbdmr assumes that DNA methylation levels follow a generalized beta distribution. We compare gbdmr to alternative approaches via simulations and real data analyses, including dmrff, a new DMR detection approach that shows promising performance among competitors, and the traditional EWAS that focuses on single CpG sites. Our simulations demonstrate that gbdmr is superior to the other two when the correlation between neighboring CpG sites is strong, while dmrff shows a higher power when the correlation is weak. We provide an explanation of these phenomena from a theoretical perspective. We further applied the three methods to multiple real DNA methylation datasets. One is from a birth cohort study undertaken on the Isle of Wight, United Kingdom, and the other two are from the Gene Expression Omnibus database repository. Overall, gbdmr identifies more DMR CpGs linked to phenotypes than dmrff, and the simulated results support the findings. Conclusions Gbdmr is an innovative method for detecting DMRs based on generalized beta regression. It demonstrated notable advantages over dmrff and traditional EWAS, particularly when adjacent CpGs exhibited moderate to strong correlations. Our real data analyses and simulated findings highlight the reliability of gbdmr as a robust DMR detection tool. The gbdmr approach is accessible and implemented by R on GitHub: https://github.com/chengzhouwu/gbdmr .https://doi.org/10.1186/s12859-024-05711-yDifferentially methylated regionsGeneralized beta distributionDNA methylationCpG site |
| spellingShingle | Chengzhou Wu Xichen Mou Hongmei Zhang Gbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressions BMC Bioinformatics Differentially methylated regions Generalized beta distribution DNA methylation CpG site |
| title | Gbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressions |
| title_full | Gbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressions |
| title_fullStr | Gbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressions |
| title_full_unstemmed | Gbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressions |
| title_short | Gbdmr: identifying differentially methylated CpG regions in the human genome via generalized beta regressions |
| title_sort | gbdmr identifying differentially methylated cpg regions in the human genome via generalized beta regressions |
| topic | Differentially methylated regions Generalized beta distribution DNA methylation CpG site |
| url | https://doi.org/10.1186/s12859-024-05711-y |
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