Domain-Level Annotations and Conservation Scores for Human Endogenous Retroviruses

💡Introduction: This dataset provides a comprehensive, genome-wide annotation of conserved retroviral protein domains within human endogenous retroviruses (HERVs). Using a reproducible pipeline based on RepeatMasker, EMBOSS getorf, HMMER, and InterProScan, we analyzed over 120,000 open reading frames (ORFs) derived from internal HERV regions annotated in the human reference genome (GRCh38). We identified 17,540 retroviral-like domain hits, including domains from reverse transcriptase, RNase H, integrase, protease, Gag, Env, and accessory proteins. Thousands of domains showed moderate to high conservation, with more than 1,000 exhibiting near-complete alignment to reference HMM profiles. We further refined these annotations using InterProScan and Phobius to identify conserved catalytic residues, structural motifs, and transmembrane features—enabling a detailed assessment of the functional potential of each locus. 🧬 The dataset includes: BED files with genomic coordinates of annotated domains FASTA files of predicted ORFs and extracted domain sequences InterProScan and Phobius outputs for protein domain and topology annotation Summary tables of domain conservation and co-occurrence patterns Together, these resources offer a high-resolution view of the protein-coding legacy of HERVs and support future research into their roles in host biology, immune modulation, and evolutionary co-option. 📄Description of each file: HERV_internal_sequences_v1.fasta: nucleotide sequences of merged internal HERV regions extracted from GRCh38 using RepeatMasker annotations. HERV_orfs_aa_sequences_v1.fasta: amino acid sequences of predicted ORFs derived from internal HERV regions using EMBOSS getorf. HERV_hmmscan_output_v1.tbl: raw HMMER hmmscan output table showing all detected domain matches against GyDB profiles. HERV_loci_annotated_domains_v1.tsv: filtered table summarizing the best-scoring conserved domain per domain class per ORF, including coverage and e-value. HERV_domains_v1.bed: BED file with genomic coordinates of mapped domains across the genome. HERV_domains_nt_sequences_v1.fasta: nucleotide sequences of domain-mapped regions extracted from the genome. HERV_domains_aa_sequences_v1.fasta: amino acid sequences of domain-mapped regions extracted from the original ORFs. HERV_interproscan_output_v1.zip: full InterProScan output directory with XML, TSV, and additional annotation files for each ORF. HERV_interproscan_cdd_parsed_v1.tsv: parsed summary of Conserved Domains Database (CDD) hits from InterProScan. ENV_phobius_output_v1.txt: output of Phobius transmembrane domain prediction run on ENV domain sequences. HERV_coocurrence_Gag_Pol_Env_v1.xlsx: summary table showing co-occurrence of multiple conserved domains (Gag, Pol, Env) within the same locus. HERVK_conserved_loci_v1.xlsx: list of HERVK loci with high-confidence domain architecture (e.g., full Gag–Pol–Env), including coverage scores. HERVK_conserved_loci_ORFs_annotations_v1.xlsx: detailed annotations for the ORFs in the most conserved HERVK loci. 💻Code and citation: The dataset was generated using a custom pipeline developed for this study, available at:🔗 https://github.com/funcgen/herv-domain-map If you use this dataset in your research, please cite both the dataset DOI and the corresponding article: Montserrat-Ayuso, T., & Esteve-Codina, A. (2025). A comprehensive annotation of conserved protein domains in human endogenous retroviruses. bioRxiv. https://doi.org/10.1101/2025.07.25.666750