Differential DNA Methylation Analysis without a Reference Genome
Genome-wide DNA methylation mapping uncovers epigenetic changes associated with animal development, environmental adaptation, and species evolution. To address the lack of high-throughput methods for DNA methylation analysis in non-model organisms, we developed an integrated approach for studying DN...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2015-12-01
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| Series: | Cell Reports |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2211124715013248 |
| _version_ | 1818351414695428096 |
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| author | Johanna Klughammer Paul Datlinger Dieter Printz Nathan C. Sheffield Matthias Farlik Johanna Hadler Gerhard Fritsch Christoph Bock |
| author_facet | Johanna Klughammer Paul Datlinger Dieter Printz Nathan C. Sheffield Matthias Farlik Johanna Hadler Gerhard Fritsch Christoph Bock |
| author_sort | Johanna Klughammer |
| collection | DOAJ |
| description | Genome-wide DNA methylation mapping uncovers epigenetic changes associated with animal development, environmental adaptation, and species evolution. To address the lack of high-throughput methods for DNA methylation analysis in non-model organisms, we developed an integrated approach for studying DNA methylation differences independent of a reference genome. Experimentally, our method relies on an optimized 96-well protocol for reduced representation bisulfite sequencing (RRBS), which we have validated in nine species (human, mouse, rat, cow, dog, chicken, carp, sea bass, and zebrafish). Bioinformatically, we developed the RefFreeDMA software to deduce ad hoc genomes directly from RRBS reads and to pinpoint differentially methylated regions between samples or groups of individuals (http://RefFreeDMA.computational-epigenetics.org). The identified regions are interpreted using motif enrichment analysis and/or cross-mapping to annotated genomes. We validated our method by reference-free analysis of cell-type-specific DNA methylation in the blood of human, cow, and carp. In summary, we present a cost-effective method for epigenome analysis in ecology and evolution, which enables epigenome-wide association studies in natural populations and species without a reference genome. |
| first_indexed | 2024-12-13T18:37:22Z |
| format | Article |
| id | doaj.art-0e090b4e861140aabf7f3d7ca9831b5b |
| institution | Directory Open Access Journal |
| issn | 2211-1247 |
| language | English |
| last_indexed | 2024-12-13T18:37:22Z |
| publishDate | 2015-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cell Reports |
| spelling | doaj.art-0e090b4e861140aabf7f3d7ca9831b5b2022-12-21T23:35:19ZengElsevierCell Reports2211-12472015-12-0113112621263310.1016/j.celrep.2015.11.024Differential DNA Methylation Analysis without a Reference GenomeJohanna Klughammer0Paul Datlinger1Dieter Printz2Nathan C. Sheffield3Matthias Farlik4Johanna Hadler5Gerhard Fritsch6Christoph Bock7CeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaChildren’s Cancer Research Institute, St. Anna Kinderkrebsforschung, 1090 Vienna, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaChildren’s Cancer Research Institute, St. Anna Kinderkrebsforschung, 1090 Vienna, AustriaCeMM Research Center for Molecular Medicine of the Austrian Academy of Sciences, 1090 Vienna, AustriaGenome-wide DNA methylation mapping uncovers epigenetic changes associated with animal development, environmental adaptation, and species evolution. To address the lack of high-throughput methods for DNA methylation analysis in non-model organisms, we developed an integrated approach for studying DNA methylation differences independent of a reference genome. Experimentally, our method relies on an optimized 96-well protocol for reduced representation bisulfite sequencing (RRBS), which we have validated in nine species (human, mouse, rat, cow, dog, chicken, carp, sea bass, and zebrafish). Bioinformatically, we developed the RefFreeDMA software to deduce ad hoc genomes directly from RRBS reads and to pinpoint differentially methylated regions between samples or groups of individuals (http://RefFreeDMA.computational-epigenetics.org). The identified regions are interpreted using motif enrichment analysis and/or cross-mapping to annotated genomes. We validated our method by reference-free analysis of cell-type-specific DNA methylation in the blood of human, cow, and carp. In summary, we present a cost-effective method for epigenome analysis in ecology and evolution, which enables epigenome-wide association studies in natural populations and species without a reference genome.http://www.sciencedirect.com/science/article/pii/S2211124715013248DNA methylationdifferential methylation analysisbisulfite sequencingRRBSreference genome independent analysisnon-model organismscross-species comparisoncomparative genomicsvertebrate genomescomputational epigenetics |
| spellingShingle | Johanna Klughammer Paul Datlinger Dieter Printz Nathan C. Sheffield Matthias Farlik Johanna Hadler Gerhard Fritsch Christoph Bock Differential DNA Methylation Analysis without a Reference Genome Cell Reports DNA methylation differential methylation analysis bisulfite sequencing RRBS reference genome independent analysis non-model organisms cross-species comparison comparative genomics vertebrate genomes computational epigenetics |
| title | Differential DNA Methylation Analysis without a Reference Genome |
| title_full | Differential DNA Methylation Analysis without a Reference Genome |
| title_fullStr | Differential DNA Methylation Analysis without a Reference Genome |
| title_full_unstemmed | Differential DNA Methylation Analysis without a Reference Genome |
| title_short | Differential DNA Methylation Analysis without a Reference Genome |
| title_sort | differential dna methylation analysis without a reference genome |
| topic | DNA methylation differential methylation analysis bisulfite sequencing RRBS reference genome independent analysis non-model organisms cross-species comparison comparative genomics vertebrate genomes computational epigenetics |
| url | http://www.sciencedirect.com/science/article/pii/S2211124715013248 |
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