Comparative analysis of genome-scale, base-resolution DNA methylation profiles across 580 animal species

Supplementary Website

Study overview

An atlas of DNA methylation across 580 animal species.

Methylation of cytosines is the prototypic epigenetic modification of the DNA. It has been implicated in various regulatory mechanisms throughout the animal kingdom and particularly in vertebrates. We mapped DNA methylation in 580 animal species (535 vertebrates, 45 invertebrates), resulting in 2443 genome-scale, base-resolution DNA methylation profiles of primary tissue samples from various or-gans. Reference-genome independent analysis of this comprehensive dataset quantified the association of DNA methylation with the underlying genomic DNA sequence throughout vertebrate evolution. We observed a broadly conserved link with two major transitions – once in the first vertebrates and again with the emergence of reptiles. Cross-species comparisons focusing on individual organs supported a highly conserved role of DNA methylation in defining tissue types, and cross-mapping analysis of DNA methylation at gene promoters revealed evolutionary changes for specific genes. In summary, this study establishes a large resource of vertebrate and invertebrate DNA methylomes, it showcases the power of reference-free epigenome analysis in species for which no reference genomes are availa-ble, and it contributes an epigenetic perspective to the study of vertebrate evolution.


Phylogenetic data exploration

Correlative data exploration

Cross-species prediction of DNA methylation from sequence

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Gene regulatory network of heart- and liver-specific DNA methylation


Correlative data exploration

Per-sample data can be explored using the interactive viewer below. Hover over (click on) a dot to highlight (select) all samples of a species. Double-click to deselect. (r = Pearson correlation)

Stats:

X-axis:

Y-axis:

Color:

Species:


Cross-species prediction of DNA methylation form sequence

Zoomable heatmap depicting ROC-AUC values as a measure of cross-species predictability of DNA methylation from DNA sequence. Rows represent the species used for training and columns represent the species used for testing.
To use individual models on your own datasets we provide an interactive interface with top-performing models for most of the classes.

Data download

Description Links
Raw sequencing data:
 Unmapped bam files are being submitted to the NCBI Gene Expression Omnibus (GEO) repository (GSE195869)
Processed data:
 Processed data (DNA methylation sequencing and consensus references) are being submitted to the NCBI Gene Expression Omnibus (GEO) repository (GSE195869) and can be downloaded as an archive (original size 547 GB) here.
Analysis code:
 All source code relevant for data processing and analysis (ZIP)
SVM models:
 Pretrained SVM models for predicting DNA methylation status, shared as RDS objects. (tar.gz)
Methylation values:
 Mean methylation values for each deduced reference fragment: cpg, cphph, cphpg.
Promoter orthology:
 Promoter orthology file (ZIP).

Collection of publicly available reference genomes

A collection of reference genomes used for cross-mapping and validation with download links and overview of genomic sequence features(tsv).

Search table:

Common Name Scientific Name Taxonomic group Genome Total basepairs N chromosomes A freq. C freq. G freq. T freq. CpG freq. CpG obs./exp. Repeats freq. Download link
Sea Hare Aplysia californica Invertebrata aplCal1 715806041 8767 0.300 0.201 0.201 0.299 0.025 0.627 0.083 link
Lancelet Cephalochordata Invertebrata braFlo1 926386587 2 0.294 0.206 0.206 0.294 0.028 0.663 0.063 link
C. intestinalis C. intestinalis Invertebrata ci3 115227500 1272 0.322 0.178 0.178 0.322 0.028 0.867 0.149 link
S. purpuratus Strongylocentrotus purpuratus Invertebrata strPur2 907085737 114223 0.315 0.185 0.185 0.315 0.023 0.676 0.129 link
Elephant shark Callorhinchus milii Chondrichthyes calMil1 974498586 21204 0.288 0.212 0.212 0.288 0.020 0.445 0.271 link
Coelacanth Latimeria chalumnae Actinopteri latCha1 2860591921 22819 0.294 0.206 0.206 0.294 0.012 0.277 0.071 link
Tetraodon Tetraodon nigroviridis Actinopteri tetNig2 358618246 27 0.268 0.232 0.232 0.268 0.032 0.603 0.046 link
Fugu Takifugu rubripes Actinopteri fr3 391484715 6835 0.273 0.227 0.227 0.273 0.029 0.565 0.073 link
Zebrafish Danio rerio Actinopteri danRer11 1679203469 1923 0.317 0.183 0.183 0.317 0.018 0.530 0.545 link
Nile tilapia Oreochromis niloticus Actinopteri oreNil2 927696114 5678 0.298 0.202 0.202 0.298 0.016 0.399 0.033 link
Medaka Oryzias latipes Actinopteri oryLat2 869000216 7189 0.298 0.202 0.202 0.298 0.020 0.483 0.027 link
Atlantic cod Gadus morhua Actinopteri gadMor1 824327835 427428 0.274 0.227 0.229 0.270 0.031 0.590 0.081 link
Stickleback Gasterosteus aculeatus Actinopteri gasAcu1 463354448 23 0.277 0.223 0.223 0.277 0.033 0.658 0.036 link
Axolotl Ambystoma mexicanum Amphibia AmexG_v6.0-DD 26730690244 28 0.270 0.230 0.230 0.270 0.025 0.469 NaN link
X. tropicalis Xenopus tropicalis Amphibia xenTro9 1440398454 6822 0.300 0.200 0.200 0.300 0.014 0.340 0.337 link
African clawed frog Xenopus laevis Amphibia xenLae2 2718433805 108033 0.305 0.195 0.195 0.305 0.015 0.393 0.114 link
Tibetan frog Nanorana parkeri Amphibia nanPar1 2053849526 25187 0.287 0.213 0.213 0.287 0.020 0.434 0.013 link
Garter snake Thamnophis sirtalis Reptilia thaSir1 1424897867 7930 0.300 0.200 0.200 0.300 0.012 0.303 0.044 link
American alligator Alligator mississippiensis Reptilia allMis1 2174259888 14645 0.278 0.222 0.222 0.278 0.010 0.207 0.378 link
Painted turtle Chrysemys picta Reptilia chrPic1 2589745704 80984 0.279 0.221 0.221 0.279 0.014 0.281 0.027 link
Lizard Anolis carolinensis Reptilia anoCar2 1799143587 6457 0.298 0.202 0.202 0.298 0.012 0.292 0.076 link
Turkey Meleagris gallopavo Aves melGal5 1128339136 231286 0.293 0.207 0.207 0.292 0.011 0.252 0.081 link
Medium ground finch Geospiza fortis Aves geoFor1 1065292181 27239 0.292 0.208 0.208 0.292 0.007 0.157 0.057 link
Chicken Gallus gallus Aves galGal6 1065365425 464 0.289 0.211 0.211 0.289 0.012 0.276 0.126 link
Zebra finch Taeniopygia guttata Aves taeGut2 1232135591 37096 0.293 0.207 0.207 0.293 0.008 0.185 0.080 link
Brown kiwi Apteryx australis Aves aptMan1 1523986457 24719 0.294 0.206 0.206 0.294 0.012 0.281 0.038 link
Golden eagle Aquila chrysaetos Aves aquChr2 1192725744 1141 0.291 0.209 0.209 0.291 0.012 0.282 0.053 link
Budgerigar Melopsittacus undulatus Aves melUnd1 1117373619 25212 0.294 0.206 0.206 0.294 0.007 0.168 0.072 link
Wallaby Notamacropus eugenii Marsupialia macEug2 3075184024 277711 0.306 0.194 0.194 0.306 0.005 0.133 0.393 link
Opossum Monodelphis domestica Marsupialia monDom5 3605631728 11 0.311 0.189 0.189 0.311 0.005 0.135 0.545 link
Tasmanian devil Sarcophilus harrisii Marsupialia sarHar1 3174693010 35974 0.320 0.180 0.180 0.320 0.004 0.131 0.397 link
Shrew Sorex araneus Mammalia sorAra2 2423158183 12845 0.286 0.214 0.214 0.286 0.014 0.315 0.297 link
Bonobo Pan paniscus Mammalia panPan2 3286643896 10274 0.296 0.204 0.204 0.296 0.010 0.229 0.421 link
Chimp Pan troglodytes Mammalia panTro6 3050398082 4346 0.296 0.204 0.204 0.297 0.010 0.249 0.530 link
Gorilla Gorilla gorilla Mammalia gorGor6 3044872214 5486 0.297 0.203 0.203 0.297 0.010 0.253 0.496 link
Gibbon Nomascus leucogenys Mammalia nomLeu3 2962077449 17492 0.296 0.204 0.204 0.296 0.010 0.241 0.477 link
Human Homo sapiens Mammalia hg38 3209286105 455 0.295 0.204 0.205 0.296 0.010 0.242 0.505 link
Proboscis Monkey Nasalis larvatus Mammalia nasLar1 3011982740 319550 0.299 0.201 0.202 0.299 0.009 0.218 0.371 link
Golden snub-nosed monkey Rhinopithecus roxellana Mammalia rhiRox1 2899552139 135512 0.295 0.204 0.204 0.296 0.010 0.244 0.504 link
Rhesus Macaca mulatta Mammalia rheMac10 2971331530 2939 0.295 0.205 0.205 0.295 0.011 0.252 0.518 link
Green Monkey Chlorocebus sabaeus Mammalia chlSab2 2789656328 2004 0.296 0.204 0.204 0.296 0.010 0.242 0.481 link
Crab-eating macaque Macaca fascicularis Mammalia macFas5 2946843737 7601 0.295 0.204 0.205 0.296 0.010 0.247 0.477 link
Tenrec Echinops telfairi Mammalia echTel2 2947024286 8402 0.286 0.215 0.215 0.284 0.014 0.292 0.251 link
Rock hyrax Procavia capensis Mammalia proCap1 2985258999 295006 0.295 0.206 0.205 0.294 0.010 0.226 0.227 link
Manatee Trichechus manatus latirostris Mammalia triMan1 3103808406 6323 0.297 0.204 0.204 0.296 0.010 0.245 0.325 link
White rhinoceros Ceratotherium simum Mammalia cerSim1 2464367180 3087 0.296 0.204 0.204 0.296 0.011 0.272 0.373 link
Cow Bos taurus Mammalia bosTau9 2715853792 2211 0.290 0.210 0.210 0.291 0.011 0.247 0.496 link
Baboon Papio anubis Mammalia papAnu4 2959373024 63235 0.295 0.205 0.205 0.295 0.011 0.257 0.522 link
Rat Rattus norvegicus Mammalia rn7 2647915728 176 0.290 0.210 0.210 0.290 0.010 0.220 0.451 link
Mouse lemur Microcebus murinus Mammalia micMur2 2438804424 10311 0.295 0.205 0.205 0.295 0.012 0.290 0.404 link
Chinese hamster Cricetulus griseus Mammalia criGri1 2360146428 52711 0.293 0.207 0.207 0.293 0.007 0.153 0.265 link
Bison Bison bison bison Mammalia bisBis1 2953622319 450182 0.290 0.210 0.210 0.290 0.011 0.247 0.448 link
Naked mole-rat Heterocephalus glaber Mammalia hetGla2 2618204639 4229 0.299 0.201 0.201 0.299 0.008 0.201 0.287 link
Hedgehog Erinaceus europaeus Mammalia eriEur2 2715720925 5803 0.292 0.208 0.208 0.292 0.009 0.201 0.399 link
Hawaiian monk seal Monachus schauinslandi Mammalia neoSch1 2400839308 7872 0.293 0.207 0.207 0.293 0.012 0.271 0.426 link
Elephant Loxodonta africana Mammalia loxAfr3 3196760833 2353 0.296 0.204 0.204 0.296 0.010 0.247 0.466 link
Orangutan Pongo abelii Mammalia ponAbe3 3065052215 5261 0.296 0.204 0.204 0.296 0.010 0.234 0.265 link
Mouse Mus musculus Mammalia mm39 2728222451 61 0.292 0.208 0.208 0.292 0.008 0.190 0.440 link
Microbat Myotis lucifugus Mammalia myoLuc2 2034575300 11654 0.288 0.212 0.212 0.288 0.013 0.291 0.326 link
Tree shrew Tupaia belangeri Mammalia tupBel1 3660774957 150851 0.293 0.207 0.207 0.293 0.012 0.290 0.119 link
Guinea pig Cavia porcellus Mammalia cavPor3 2723219641 3144 0.300 0.200 0.200 0.300 0.009 0.216 0.270 link
Rabbit Oryctolagus cuniculus Mammalia oryCun2 2737490501 3242 0.281 0.219 0.219 0.282 0.014 0.289 0.417 link
Squirrel Ictidomys tridecemlineatus Mammalia speTri2 2478393770 12483 0.301 0.200 0.199 0.300 0.008 0.193 0.341 link
Horse Equus caballus Mammalia equCab3 2506966135 4701 0.292 0.208 0.208 0.293 0.012 0.289 0.445 link
Ferret Mustela putorius furo Mammalia musFur1 2410758013 7741 0.293 0.207 0.207 0.292 0.012 0.267 0.369 link
Pig Sus scrofa Mammalia susScr11 2501912388 613 0.290 0.209 0.209 0.291 0.012 0.283 0.449 link
Cat Felis catus Mammalia felCat9 2521863845 4508 0.291 0.209 0.209 0.291 0.014 0.323 0.426 link
Dog Canis lupus familiaris Mammalia canFam5 2343218756 794 0.294 0.206 0.206 0.294 0.011 0.263 0.417 link
Sheep Ovis aries Mammalia oviAri4 2615516299 5466 0.290 0.209 0.210 0.291 0.011 0.244 0.456 link
Kangaroo rat Dipodomys ordii Mammalia dipOrd1 2158502098 210053 0.283 0.214 0.209 0.293 0.012 0.260 0.205 link
Megabat Pteropus vampyrus Mammalia pteVam1 1996076410 96944 0.300 0.200 0.200 0.300 0.013 0.326 0.293 link
Squirrel monkey Saimiri boliviensis boliviensis Mammalia saiBol1 2608572064 2685 0.296 0.204 0.204 0.296 0.010 0.237 0.444 link
Sloth Choloepus hoffmanni Mammalia choHof1 2458927620 481259 0.306 0.194 0.195 0.305 0.007 0.188 0.300 link
Marmoset Callithrix jacchus Mammalia calJac4 2897824427 964 0.296 0.204 0.204 0.296 0.010 0.232 0.485 link
Armadillo Dasypus novemcinctus Mammalia dasNov3 3631522711 46559 0.296 0.204 0.204 0.296 0.010 0.252 0.451 link
Alpaca Vicugna pacos Mammalia vicPac2 2172177994 276611 0.294 0.207 0.207 0.292 0.012 0.282 0.340 link
Lamprey Petromyzon marinus Jawless Vertebrate petMar3 1130433897 12062 0.260 0.240 0.240 0.260 0.046 0.802 0.350 link

Citation

If you use these data in your research, please cite:

Klughammer* , J., Romanovskaia* , D., et al. Comparative analysis of genome-scale, base-resolution DNA methylation profiles across 580 animal species. Nature Communications 14, 232 (2023). https://doi.org/10.1038/s41467-022-34828-y
* These authors contributed equally to this work
Correspondence: cbock@cemm.oeaw.ac.at (C.B.), klughammer@genzentrum.lmu.de (J.K.)