And co-authors [30] and converted to Hg19 using the Galaxy LiftOver tool [45]. The relative enrichment of 5hmC elements in different functional categories of genes was evaluated using the Genomic Regions Enrichment of Annotations Tool (GREAT) [46], setting the basal gene regulatory domains within 5 Kb upstream and 1 Kb downstream of the transcription start site, and up to 1 Mb extended regulatory domains in both directions to the nearest gene’s basal domain [47].Ivanov et al. Genome Biology 2013, 14:R83 http://genomebiology.com/2013/14/8/RPage 13 ofLocus-specific validation of next-generation sequencing datadehydrogenase; LC-MS: liquid chromatography-mass spectrometry; lncRNA: long non-coding RNA; miRNA: microRNA; NGS: next-generation sequencing. Competing interests The authors declare that they have no competing interests. Authors’ contributions MI conceived the study, carried out sample preparation and data interpretation and drafted the manuscript. MKal carried out the data analysis. MKac participated in the design of the study and in sample preparation. IB carried out the immunohistochemistry assays and the locus-specific validation of NGS data. KK carried out the LC-MS analysis. AR provided the human fetal liver samples. LM carried out the next-generation sequencing and microarray assays. AM, LM and MIS participated in planning of the study and coordinated and financed the work from their grants. All authors carried out manuscript revisions. All authors read and approved the final manuscript. Acknowledgements The authors would like to acknowledge support from Mr Rickard Wahlstr PubMed ID:https://www.ncbi.nlm.nih.gov/pubmed/28914615 and Mr Gunnar H glund from Q Q Labs AB (G eborg, Sweden) and purchase ABT-737 Clinical Proteomics Mass Spectrometry core facility at Karolinska University Hospital and Science for Life Laboratory (Stockholm, Sweden) for providing assistance in mass spectrometry and data analysis. We also acknowledge the important help provided by Dr Lena Ekstr , Dr Inger Jonasson, Dr Chunxiao Song, Dr Chuan He, Ms Susanne Virding, Ms Heidi Martikainen, Ms Silva Kasela, Dr Paula Ann Kivistik and Mr Viljo Soo. This work is supported by grants from The Swedish Research Council, the IMI-JU project MIP-DILI (grant agreement 115336), the Seurat-1 project NOTOX, the Estonian Science Foundation (ETF9293), the European Union through the European Social Fund (MJD71) and the European Regional Development Fund, in the frame of the Centre of Excellence in Genomics; and targeted financing from the Estonian Government [SF0180142s08]. Authors’ details Section of Pharmacogenetics, Department of Physiology and Pharmacology, Karolinska Institutet, Nanna Svartz v 2, 17177 Stockholm, Sweden. 2 Estonian Genome Center, University of Tartu, Riia 23b, 51010 Tartu, Estonia. 3 Cancer Proteomics Mass Spectrometry, Department of Oncology-Pathology, Science for Life Laboratory, Karolinska Institutet Science Park, Tomtebodav en 23A, 17165 Solna, Sweden. 4Division of Clinical Pharmacology, Department of Laboratory Medicine, Karolinska University Hospital at Huddinge, Medicingatan 5, 14186 Stockholm, Sweden. 5Estonian Biocentre, Riia 23b, 51010 Tartu, Estonia. 6AQ2 Institute of Molecular and Cell Biology, University of Tartu, Riia 23b, 51010 Tartu, Estonia.To validate NGS data at single-base resolution in selected genomic intervals, we employed the TAB-Seq method [48]. Briefly, 1 of DNA was oxidized with the WiseGene 5hmC TAB-Seq kit (WiseGene, Chicago, IL, USA) following the manufacturer’s instructions [49]. Then, bot.