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Volume 51 Issue 2
Feb.  2024
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Article Navigation >  Journal of Genetics and Genomics  > 2024  >  51(2): 230-242

NCAD v1.0: a database for non-coding variant annotation and interpretation

doi: 10.1016/j.jgg.2023.12.005
  •  

    Institute of Rare Diseases, West China Hospital, Sichuan University, Chengdu, Sichuan 610044, China

Funds:

This research was financially supported by the National Natural Science Foundation of China (82171836) and the 1·3·5 project for disciplines of excellence, West China Hospital, Sichuan University (ZYJC20002).

  • Received Date: 2023-08-30
  • Accepted Date: 2023-12-18
  • Rev Recd Date: 2023-12-15
    • Available Online: 2025-06-07
  • Publish Date: 2023-12-23
    Abstract
  • The application of whole genome sequencing is expanding in clinical diagnostics across various genetic disorders, and the significance of non-coding variants in penetrant diseases is increasingly being demonstrated. Therefore, it is urgent to improve the diagnostic yield by exploring the pathogenic mechanisms of variants in non-coding regions. However, the interpretation of non-coding variants remains a significant challenge, due to the complex functional regulatory mechanisms of non-coding regions and the current limitations of available databases and tools. Hence, we develop the non-coding variant annotation database (NCAD, http://www.ncawdb.net/), encompassing comprehensive insights into 665,679,194 variants, regulatory elements, and element interaction details. Integrating data from 96 sources, spanning both GRCh37 and GRCh38 versions, NCAD v1.0 provides vital information to support the genetic diagnosis of non-coding variants, including allele frequencies of 12 diverse populations, with a particular focus on the population frequency information for 230,235,698 variants in 20,964 Chinese individuals. Moreover, it offers prediction scores for variant functionality, five categories of regulatory elements, and four types of non-coding RNAs. With its rich data and comprehensive coverage, NCAD serves as a valuable platform, empowering researchers and clinicians with profound insights into non-coding regulatory mechanisms while facilitating the interpretation of non-coding variants.
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  • Abicht, A., Stucka, R., Schmidt, C., Briguet, A., Hopfner, S., Song, I.H., Pongratz, D., Muller-Felber, W., Ruegg, M.A., Lochmuller, H., 2002. A newly identified chromosomal microdeletion and an N-box mutation of the AChR epsilon gene cause a congenital myasthenic syndrome. Brain 125, 1005-1013.
    Abugessaisa, I., Ramilowski, J.A., Lizio, M., Severin, J., Hasegawa, A., Harshbarger, J., Kondo, A., Noguchi, S., Yip, C.W., Ooi, J.L.C., et al., 2021. FANTOM enters 20th year: expansion of transcriptomic atlases and functional annotation of non-coding RNAs. Nucleic Acids Res. 49, D892-D898.
    Akhtar-Zaidi, B., Cowper-Sal-lari, R., Corradin, O., Saiakhova, A., Bartels, C.F., Balasubramanian, D., Myeroff, L., Lutterbaugh, J., Jarrar, A., Kalady, M.F., et al., 2012. Epigenomic enhancer profiling defines a signature of colon cancer. Science 336, 736-739.
    Bai, X., Shi, S., Ai, B., Jiang, Y., Liu, Y., Han, X., Xu, M., Pan, Q., Wang, F., Wang, Q., et al., 2020. ENdb: a manually curated database of experimentally supported enhancers for human and mouse. Nucleic Acids Res. 48, D51-D57.
    Bandyopadhyay, S., Bhattacharyya, M., 2010. PuTmiR: a database for extracting neighboring transcription factors of human microRNAs. BMC Bioinformatics 11, 190.
    Bao, Z., Yang, Z., Huang, Z., Zhou, Y., Cui, Q., Dong, D., 2019. LncRNADisease 2.0: an updated database of long non-coding RNA-associated diseases. Nucleic Acids Res. 47, D1034-D1037.
    Bauer, D.E., Kamran, S.C., Lessard, S., Xu, J., Fujiwara, Y., Lin, C., Shao, Z., Canver, M.C., Smith, E.C., Pinello, L., et al., 2013. An erythroid enhancer of BCL11A subject to genetic variation determines fetal hemoglobin level. Science 342, 253-257.
    Belkadi, A., Bolze, A., Itan, Y., Cobat, A., Vincent, Q.B., Antipenko, A., Shang, L., Boisson, B., Casanova, J.L., Abel, L., 2015. Whole-genome sequencing is more powerful than whole-exome sequencing for detecting exome variants. Proc. Natl. Acad. Sci. U. S. A. 112, 5473-5478.
    Bhattacharya, A., Cui, Y., 2016. SomamiR 2.0: a database of cancer somatic mutations altering microRNA-ceRNA interactions. Nucleic Acids Res. 44, D1005-D1010.
    Boyle, A.P., Hong, E.L., Hariharan, M., Cheng, Y., Schaub, M.A., Kasowski, M., Karczewski, K.J., Park, J., Hitz, B.C., Weng, S., et al., 2012. Annotation of functional variation in personal genomes using RegulomeDB. Genome Res. 22, 1790-1797.
    Cao, Y., Li, L., Xu, M., Feng, Z., Sun, X., Lu, J., Xu, Y., Du, P., Wang, T., Hu, R., et al., 2020. The ChinaMAP analytics of deep whole genome sequences in 10,588 individuals. Cell Res. 30, 717-731.
    Chang, L., Xia, J., 2023. MicroRNA regulatory network analysis using miRNet 2.0. Methods Mol. Biol. 2594, 185-204.
    Chen, J., Lin, J., Hu, Y., Ye, M., Yao, L., Wu, L., Zhang, W., Wang, M., Deng, T., Guo, F., et al., 2023. RNADisease v4.0: an updated resource of RNA-associated diseases, providing RNA-disease analysis, enrichment and prediction. Nucleic Acids Res. 51, D1397-D1404.
    Chen, Y., Yao, L., Tang, Y., Jhong, J.H., Wan, J., Chang, J., Cui, S., Luo, Y., Cai, X., Li, W., et al., 2022. CircNet 2.0: an updated database for exploring circular RNA regulatory networks in cancers. Nucleic Acids Res. 50, D93-D101.
    Cong, P.K., Bai, W.Y., Li, J.C., Yang, M.Y., Khederzadeh, S., Gai, S.R., Li, N., Liu, Y.H., Yu, S.H., Zhao, W.W., et al., 2022. Genomic analyses of 10,376 individuals in the Westlake BioBank for Chinese (WBBC) pilot project. Nat. Commun. 13, 2939.
    Conte, I., Hadfield, K.D., Barbato, S., Carrella, S., Pizzo, M., Bhat, R.S., Carissimo, A., Karali, M., Porter, L.F., Urquhart, J., et al., 2015. MiR-204 is responsible for inherited retinal dystrophy associated with ocular coloboma. Proc. Natl. Acad. Sci. U. S. A. 112, E3236-E3245.
    Cunningham, F., Allen, J.E., Allen, J., Alvarez-Jarreta, J., Amode, M.R., Armean, I.M., Austine-Orimoloye, O., Azov, A.G., Barnes, I., Bennett, R., et al., 2022. Ensembl 2022. Nucleic Acids Res. 50, D988-D995.
    Das, T., Deb, A., Parida, S., Mondal, S., Khatua, S., Ghosh, Z., 2021. LncRBase V.2: an updated resource for multispecies lncRNAs and ClinicLSNP hosting genetic variants in lncRNAs for cancer patients. RNA Biol. 18, 1136-1151.
    Diesh, C., Stevens, G.J., Xie, P., De Jesus Martinez, T., Hershberg, E.A., Leung, A., Guo, E., Dider, S., Zhang, J., Bridge, C., et al., 2023. JBrowse 2: a modular genome browser with views of synteny and structural variation. Genome Biol. 24, 74.
    Duclert, A., Savatier, N., Schaeffer, L., Changeux, J.P., 1996. Identification of an element crucial for the sub-synaptic expression of the acetylcholine receptor epsilon-subunit gene. J. Biol. Chem. 271, 17433-17438.
    Ellingford, J.M., Ahn, J.W., Bagnall, R.D., Baralle, D., Barton, S., Campbell, C., Downes, K., Ellard, S., Duff-Farrier, C., FitzPatrick, D.R., et al., 2022. Recommendations for clinical interpretation of variants found in non-coding regions of the genome. Genome Med. 14, 73.
    Frankish, A., Carbonell-Sala, S., Diekhans, M., Jungreis, I., Loveland, J.E., Mudge, J.M., Sisu, C., Wright, J.C., Arnan, C., Barnes, I., et al., 2023. GENCODE: reference annotation for the human and mouse genomes in 2023. Nucleic Acids Res. 51, D942-D949.
    French, J.D., Edwards, S.L., 2020. The Role of Noncoding Variants in Heritable Disease. Trends Genet. 36, 880-891.
    Fromm, B., Hoye, E., Domanska, D., Zhong, X., Aparicio-Puerta, E., Ovchinnikov, V., Umu, S.U., Chabot, P.J., Kang, W., Aslanzadeh, M., et al., 2022. MirGeneDB 2.1: toward a complete sampling of all major animal phyla. Nucleic Acids Res. 50, D204-D210.
    Gao, T., Qian, J., 2020. EnhancerAtlas 2.0: an updated resource with enhancer annotation in 586 tissue/cell types across nine species. Nucleic Acids Res. 48, D58-D64.
    Consortium, G.T., 2013. The Genotype-Tissue Expression (GTEx) project. Nat. Genet. 45, 580-585.
    Ghosh, B., Sarkar, A., Mondal, S., Bhattacharya, N., Khatua, S., Ghosh, Z., 2022. piRNAQuest V.2: an updated resource for searching through the piRNAome of multiple species. RNA Biol. 19, 12-25.
    Giacopuzzi, E., Popitsch, N., Taylor, J.C., 2022. GREEN-DB: a framework for the annotation and prioritization of non-coding regulatory variants from whole-genome sequencing data. Nucleic Acids Res. 50, 2522-2535.
    Glazar, P., Papavasileiou, P., Rajewsky, N., 2014. circBase: a database for circular RNAs. RNA 20, 1666-1670.
    Gong, J., Mei, S., Liu, C., Xiang, Y., Ye, Y., Zhang, Z., Feng, J., Liu, R., Diao, L., Guo, A.Y., et al., 2018. PancanQTL: systematic identification of cis-eQTLs and trans-eQTLs in 33 cancer types. Nucleic Acids Res. 46, D971-D976.
    Guo, J., Huang, X., Zhang, C., Huang, P., Li, Y., Wen, F., Wang, X., Yang, N., Xu, M., Bi, Y., et al., 2022. The blood virome of 10,585 individuals from the ChinaMAP. Cell Discov. 8, 113.
    Guo, L., Wang, J., 2018. rSNPBase 3.0: an updated database of SNP-related regulatory elements, element-gene pairs and SNP-based gene regulatory networks. Nucleic Acids Res. 46, D1111-D1116.
    Hait, T.A., Amar, D., Shamir, R., Elkon, R., 2018. FOCS: a novel method for analyzing enhancer and gene activity patterns infers an extensive enhancer-promoter map. Genome Biol. 19, 56.
    Hernandez, R.D., Uricchio, L.H., Hartman, K., Ye, C., Dahl, A., Zaitlen, N., 2019. Ultrarare variants drive substantial cis heritability of human gene expression. Nat. Genet. 51, 1349-1355.
    Hu, Y., Lu, Q., Powles, R., Yao, X., Yang, C., Fang, F., Xu, X., Zhao, H., 2017. Leveraging functional annotations in genetic risk prediction for human complex diseases. PLoS Comput. Biol. 13, e1005589.
    Huang, H.Y., Lin, Y.C., Cui, S., Huang, Y., Tang, Y., Xu, J., Bao, J., Li, Y., Wen, J., Zuo, H., et al., 2022. miRTarBase update 2022: an informative resource for experimentally validated miRNA-target interactions. Nucleic Acids Res. 50, D222-D230.
    Ioannidis, N.M., Davis, J.R., DeGorter, M.K., Larson, N.B., McDonnell, S.K., French, A.J., Battle, A.J., Hastie, T.J., Thibodeau, S.N., Montgomery, S.B., et al., 2017. FIRE: functional inference of genetic variants that regulate gene expression. Bioinformatics 33, 3895-3901.
    Jiang, Q., Wang, Y., Hao, Y., Juan, L., Teng, M., Zhang, X., Li, M., Wang, G., Liu, Y., 2009. miR2Disease: a manually curated database for microRNA deregulation in human disease. Nucleic Acids Res. 37, D98-D104.
    Karczewski, K.J., Francioli, L.C., Tiao, G., Cummings, B.B., Alfoldi, J., Wang, Q., Collins, R.L., Laricchia, K.M., Ganna, A., Birnbaum, D.P., et al., 2020. The mutational constraint spectrum quantified from variation in 141,456 humans. Nature 581, 434-443.
    Kertesz, M., Iovino, N., Unnerstall, U., Gaul, U., Segal, E., 2007. The role of site accessibility in microRNA target recognition. Nat. Genet. 39, 1278-1284.
    Khan, A., Zhang, X., 2016. dbSUPER: a database of super-enhancers in mouse and human genome. Nucleic Acids Res. 44, D164-D171.
    Khan, S., Mujahid, T.A., Ishaq, M., Bukhari, S.A.R., Saeed, I., 2018. Benign migratory glossitis. J. Coll. Physicians Surg. Pak. 28, 175-176.
    Kozomara, A., Birgaoanu, M., Griffiths-Jones, S., 2019. miRBase: from microRNA sequences to function. Nucleic Acids Res. 47, D155-D162.
    Landrum, M.J., Lee, J.M., Benson, M., Brown, G.R., Chao, C., Chitipiralla, S., Gu, B., Hart, J., Hoffman, D., Jang, W., et al., 2018. ClinVar: improving access to variant interpretations and supporting evidence. Nucleic Acids Res. 46, D1062-D1067.
    Lee, P.H., Lee, C., Li, X., Wee, B., Dwivedi, T., Daly, M., 2018. Principles and methods of in-silico prioritization of non-coding regulatory variants. Hum. Genet. 137, 15-30.
    Leslie, R., O'Donnell, C.J., Johnson, A.D., 2014. GRASP: analysis of genotype-phenotype results from 1390 genome-wide association studies and corresponding open access database. Bioinformatics 30, i185-i194.
    Li, B., Leal, S.M., 2008. Methods for detecting associations with rare variants for common diseases: application to analysis of sequence data. Am. J. Hum. Genet. 83, 311-321.
    Li, H., 2011. A statistical framework for SNP calling, mutation discovery, association mapping and population genetical parameter estimation from sequencing data. Bioinformatics 27, 2987-2993.
    Li, J., Woods, S.L., Healey, S., Beesley, J., Chen, X., Lee, J.S., Sivakumaran, H., Wayte, N., Nones, K., Waterfall, J.J., et al., 2016a. Point mutations in Exon 1B of APC reveal gastric adenocarcinoma and proximal polyposis of the stomach as a familial adenomatous polyposis variant. Am. J. Hum. Genet. 98, 830-842.
    Li, M.J., Liu, Z., Wang, P., Wong, M.P., Nelson, M.R., Kocher, J.P., Yeager, M., Sham, P.C., Chanock, S.J., Xia, Z., Wang, J., 2016b. GWASdb v2: an update database for human genetic variants identified by genome-wide association studies. Nucleic Acids Res. 44, D869-D876.
    Li, X., Li, Z., Zhou, H., Gaynor, S.M., Liu, Y., Chen, H., Sun, R., Dey, R., Arnett, D.K., Aslibekyan, S., et al., 2020. Dynamic incorporation of multiple in silico functional annotations empowers rare variant association analysis of large whole-genome sequencing studies at scale. Nat. Genet. 52, 969-983.
    Li, X., Yung, G., Zhou, H., Sun, R., Li, Z., Hou, K., Zhang, M.J., Liu, Y., Arapoglou, T., Wang, C., et al., 2022a. A multi-dimensional integrative scoring framework for predicting functional variants in the human genome. Am. J. Hum. Genet. 109, 446-456.
    Li, Z., Li, X., Zhou, H., Gaynor, S.M., Selvaraj, M.S., Arapoglou, T., Quick, C., Liu, Y., Chen, H., Sun, R., et al., 2022b. A framework for detecting noncoding rare-variant associations of large-scale whole-genome sequencing studies. Nat. Methods 19, 1599-1611.
    Li, Z., Liu, L., Feng, C., Qin, Y., Xiao, J., Zhang, Z., Ma, L., 2023. LncBook 2.0: integrating human long non-coding RNAs with multi-omics annotations. Nucleic Acids Res. 51, D186-D191.
    Liang, L., Morar, N., Dixon, A.L., Lathrop, G.M., Abecasis, G.R., Moffatt, M.F., Cookson, W.O., 2013. A cross-platform analysis of 14,177 expression quantitative trait loci derived from lymphoblastoid cell lines. Genome Res. 23, 716-726.
    Liu, M., Wang, Q., Shen, J., Yang, B.B., Ding, X., 2019. Circbank: a comprehensive database for circRNA with standard nomenclature. RNA Biol. 16, 899-905.
    Lu, Q., Hu, Y., Sun, J., Cheng, Y., Cheung, K.H., Zhao, H., 2015. A statistical framework to predict functional non-coding regions in the human genome through integrated analysis of annotation data. Sci. Rep. 5, 10576.
    Lu, Q., Powles, R.L., Abdallah, S., Ou, D., Wang, Q., Hu, Y., Lu, Y., Liu, W., Li, B., Mukherjee, S., et al., 2017. Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer's disease. PLoS Genet. 13, e1006933.
    Lu, Q., Powles, R.L., Wang, Q., He, B.J., Zhao, H., 2016a. Integrative tissue-specific functional annotations in the human genome provide novel insights on many complex traits and improve signal prioritization in genome wide association studies. PLoS Genet. 12, e1005947.
    Lu, Q., Yao, X., Hu, Y., Zhao, H., 2016b. GenoWAP: GWAS signal prioritization through integrated analysis of genomic functional annotation. Bioinformatics 32, 542-548.
    Luo, Y., Hitz, B.C., Gabdank, I., Hilton, J.A., Kagda, M.S., Lam, B., Myers, Z., Sud, P., Jou, J., Lin, K., et al., 2020. New developments on the Encyclopedia of DNA Elements (ENCODE) data portal. Nucleic Acids Res. 48, D882-D889.
    Marceca, G.P., Distefano, R., Tomasello, L., Lagana, A., Russo, F., Calore, F., Romano, G., Bagnoli, M., Gasparini, P., Ferro, A., et al., 2021. MiREDiBase, a manually curated database of validated and putative editing events in microRNAs. Sci. Data 8, 199.
    McCarthy, S., Das, S., Kretzschmar, W., Delaneau, O., Wood, A.R., Teumer, A., Kang, H.M., Fuchsberger, C., Danecek, P., Sharp, K., et al., 2016. A reference panel of 64,976 haplotypes for genotype imputation. Nat. Genet. 48, 1279-1283.
    McGeary, S.E., Lin, K.S., Shi, C.Y., Pham, T.M., Bisaria, N., Kelley, G.M., Bartel, D.P., 2019. The biochemical basis of microRNA targeting efficacy. Science 366, eaav1741.
    McLaren, W., Gil, L., Hunt, S.E., Riat, H.S., Ritchie, G.R., Thormann, A., Flicek, P., Cunningham, F., 2016. The ensembl variant effect predictor. Genome Biol. 17, 122.
    Meylan, P., Dreos, R., Ambrosini, G., Groux, R., Bucher, P., 2020. EPD in 2020: enhanced data visualization and extension to ncRNA promoters. Nucleic Acids Res. 48, D65-D69.
    Nichols, P., Croxen, R., Vincent, A., Rutter, R., Hutchinson, M., Newsom-Davis, J., Beeson, D., 1999. Mutation of the acetylcholine receptor epsilon-subunit promoter in congenital myasthenic syndrome. Ann. Neurol. 45, 439-443.
    Ohno, K., Anlar, B., Engel, A.G., 1999. Congenital myasthenic syndrome caused by a mutation in the Ets-binding site of the promoter region of the acetylcholine receptor epsilon subunit gene. Neuromuscul. Disord. 9, 131-135.
    Pan, Q., Liu, Y.J., Bai, X.F., Han, X.L., Jiang, Y., Ai, B., Shi, S.S., Wang, F., Xu, M.C., Wang, Y.Z., et al., 2021. VARAdb: a comprehensive variation annotation database for human. Nucleic Acids Res. 49, D1431-D1444.
    Panciera, F., Chou, Y.C., Reuter, M.C., Zakharov, D., Stach, E.A., Hofmann, S., Ross, F.M., 2015. Synthesis of nanostructures in nanowires using sequential catalyst reactions. Nat. Mater. 14, 820-825.
    Pang, B., Snyder, M.P., 2020. Systematic identification of silencers in human cells. Nat. Genet. 52, 254-263.
    Pejaver, V., Byrne, A.B., Feng, B.J., Pagel, K.A., Mooney, S.D., Karchin, R., O'Donnell-Luria, A., Harrison, S.M., Tavtigian, S.V., Greenblatt, M.S., et al., 2022. Calibration of computational tools for missense variant pathogenicity classification and ClinGen recommendations for PP3/BP4 criteria. Am. J. Hum. Genet. 109, 2163-2177.
    Pinero, J., Ramirez-Anguita, J.M., Sauch-Pitarch, J., Ronzano, F., Centeno, E., Sanz, F., Furlong, L.I., 2020. The DisGeNET knowledge platform for disease genomics: 2019 update. Nucleic Acids Res. 48, D845-D855.
    Pomerantz, M.M., Ahmadiyeh, N., Jia, L., Herman, P., Verzi, M.P., Doddapaneni, H., Beckwith, C.A., Chan, J.A., Hills, A., Davis, M., et al., 2009. The 8q24 cancer risk variant rs6983267 shows long-range interaction with MYC in colorectal cancer. Nat. Genet. 41, 882-884.
    Rasmussen, S.A., Hamosh, A., curators, O., 2020. What's in a name? Issues to consider when naming Mendelian disorders. Genet. Med. 22, 1573-1575.
    Richards, S., Aziz, N., Bale, S., Bick, D., Das, S., Gastier-Foster, J., Grody, W.W., Hegde, M., Lyon, E., Spector, E., et al., 2015. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet. Med. 17, 405-424.
    Riethoven, J.J., 2010. Regulatory regions in DNA: promoters, enhancers, silencers, and insulators. Methods Mol. Biol. 674, 33-42.
    Ritchie, G.R., Dunham, I., Zeggini, E., Flicek, P., 2014. Functional annotation of noncoding sequence variants. Nat. Methods 11, 294-296.
    Rudloff, U., 2018. Gastric adenocarcinoma and proximal polyposis of the stomach: diagnosis and clinical perspectives. Clin. Exp. Gastroenterol. 11, 447-459.
    Sai Lakshmi, S., Agrawal, S., 2008. piRNABank: a web resource on classified and clustered Piwi-interacting RNAs. Nucleic Acids Res. 36, D173-D177.
    Satterlee, J.S., Chadwick, L.H., Tyson, F.L., McAllister, K., Beaver, J., Birnbaum, L., Volkow, N.D., Wilder, E.L., Anderson, J.M., Roy, A.L., 2019. The NIH Common Fund/Roadmap Epigenomics Program: Successes of a comprehensive consortium. Sci. Adv. 5, eaaw6507.
    Schaeffer, L., Duclert, N., Huchet-Dymanus, M., Changeux, J.P., 1998. Implication of a multisubunit Ets-related transcription factor in synaptic expression of the nicotinic acetylcholine receptor. EMBO J. 17, 3078-3090.
    Sherry, S.T., Ward, M.H., Kholodov, M., Baker, J., Phan, L., Smigielski, E.M., Sirotkin, K., 2001. dbSNP: the NCBI database of genetic variation. Nucleic Acids Res. 29, 308-311.
    Shihab, H.A., Rogers, M.F., Gough, J., Mort, M., Cooper, D.N., Day, I.N., Gaunt, T.R., Campbell, C., 2015. An integrative approach to predicting the functional effects of non-coding and coding sequence variation. Bioinformatics 31, 1536-1543.
    Smedley, D., Schubach, M., Jacobsen, J.O.B., Kohler, S., Zemojtel, T., Spielmann, M., Jager, M., Hochheiser, H., Washington, N.L., McMurry, J.A., et al., 2016. A whole-genome analysis framework for effective identification of pathogenic regulatory variants in mendelian disease. Am. J. Hum. Genet. 99, 595-606.
    Sollis, E., Mosaku, A., Abid, A., Buniello, A., Cerezo, M., Gil, L., Groza, T., Gunes, O., Hall, P., Hayhurst, J., et al., 2023. The NHGRI-EBI GWAS Catalog: knowledgebase and deposition resource. Nucleic Acids Res. 51, D977-D985.
    Stavropoulos, D.J., Merico, D., Jobling, R., Bowdin, S., Monfared, N., Thiruvahindrapuram, B., Nalpathamkalam, T., Pellecchia, G., Yuen, R.K.C., Szego, M.J., et al., 2016. Whole genome sequencing expands diagnostic utility and improves clinical management in pediatric medicine. NPJ Genom. Med. 1, 15012.
    Stenson, P.D., Mort, M., Ball, E.V., Chapman, M., Evans, K., Azevedo, L., Hayden, M., Heywood, S., Millar, D.S., Phillips, A.D., Cooper, D.N., 2020. The Human Gene Mutation Database (HGMD((R))): optimizing its use in a clinical diagnostic or research setting. Hum. Genet. 139, 1197-1207.
    Tadaka, S., Hishinuma, E., Komaki, S., Motoike, I.N., Kawashima, J., Saigusa, D., Inoue, J., Takayama, J., Okamura, Y., Aoki, Y., et al., 2021. jMorp updates in 2020: large enhancement of multi-omics data resources on the general Japanese population. Nucleic Acids Res. 49, D536-D544.
    Teng, L., He, B., Wang, J., Tan, K., 2016. 4DGenome: a comprehensive database of chromatin interactions. Bioinformatics 32, 2727.
    Consortium, E.P., 2012. An integrated encyclopedia of DNA elements in the human genome. Nature 489, 57-74.
    Tomaselli, P.J., Rossor, A.M., Horga, A., Jaunmuktane, Z., Carr, A., Saveri, P., Piscosquito, G., Pareyson, D., Laura, M., Blake, J.C., et al., 2017. Mutations in noncoding regions of GJB1 are a major cause of X-linked CMT. Neurology 88, 1445-1453.
    van der Wijst, M., de Vries, D.H., Groot, H.E., Trynka, G., Hon, C.C., Bonder, M.J., Stegle, O., Nawijn, M.C., Idaghdour, Y., van der Harst, P., et al., 2020. The single-cell eQTLGen consortium. Elife 9, e52155.
    Vitsios, D., Dhindsa, R.S., Middleton, L., Gussow, A.B., Petrovski, S., 2021. Prioritizing non-coding regions based on human genomic constraint and sequence context with deep learning. Nat. Commun. 12, 1504.
    Volders, P.J., Anckaert, J., Verheggen, K., Nuytens, J., Martens, L., Mestdagh, P., Vandesompele, J., 2019. LNCipedia 5: towards a reference set of human long non-coding RNAs. Nucleic Acids Res. 47, D135-D139.
    Wainschtein, P., Jain, D., Zheng, Z., Group, T.O.A.W., Consortium, N.T.-O.f.P.M., Cupples, L.A., Shadyab, A.H., McKnight, B., Shoemaker, B.M., Mitchell, B.D., et al., 2022. Assessing the contribution of rare variants to complex trait heritability from whole-genome sequence data. Nat. Genet. 54, 263-273.
    Wang, J., Dai, X., Berry, L.D., Cogan, J.D., Liu, Q., Shyr, Y., 2019. HACER: an atlas of human active enhancers to interpret regulatory variants. Nucleic Acids Res. 47, D106-D112.
    Wang, J., Huang, D., Zhou, Y., Yao, H., Liu, H., Zhai, S., Wu, C., Zheng, Z., Zhao, K., Wang, Z., et al., 2020. CAUSALdb: a database for disease/trait causal variants identified using summary statistics of genome-wide association studies. Nucleic Acids Res. 48, D807-D816.
    Wang, J., Shi, Y., Zhou, H., Zhang, P., Song, T., Ying, Z., Yu, H., Li, Y., Zhao, Y., Zeng, X., et al., 2022. piRBase: integrating piRNA annotation in all aspects. Nucleic Acids Res. 50, D265-D272.
    Wang, K., Li, M., Hakonarson, H., 2010a. ANNOVAR: functional annotation of genetic variants from high-throughput sequencing data. Nucleic Acids Res. 38, e164.
    Wang, S., Zhou, S., Liu, H., Meng, Q., Ma, X., Liu, H., Wang, L., Jiang, W., 2020b. ncRI: a manually curated database for experimentally validated non-coding RNAs in inflammation. BMC Genomics 21, 380.
    Wang, Y., Song, C., Zhao, J., Zhang, Y., Zhao, X., Feng, C., Zhang, G., Zhu, J., Wang, F., Qian, F., et al., 2023. SEdb 2.0: a comprehensive super-enhancer database of human and mouse. Nucleic Acids Res. 51, D280-D290.
    Wang, Z., Zhang, Q., Zhang, W., Lin, J.R., Cai, Y., Mitra, J., Zhang, Z.D., 2018. HEDD: Human Enhancer Disease Database. Nucleic Acids Res. 46, D113-D120.
    Ward, L.D., Kellis, M., 2016. HaploReg v4: systematic mining of putative causal variants, cell types, regulators and target genes for human complex traits and disease. Nucleic Acids Res. 44, D877-D881.
    Wells, A., Heckerman, D., Torkamani, A., Yin, L., Sebat, J., Ren, B., Telenti, A., di Iulio, J., 2019. Ranking of non-coding pathogenic variants and putative essential regions of the human genome. Nat. Commun. 10, 5241.
    Worthley, D.L., Phillips, K.D., Wayte, N., Schrader, K.A., Healey, S., Kaurah, P., Shulkes, A., Grimpen, F., Clouston, A., Moore, D., et al., 2012. Gastric adenocarcinoma and proximal polyposis of the stomach (GAPPS): a new autosomal dominant syndrome. Gut 61, 774-779.
    Wu, M.C., Lee, S., Cai, T., Li, Y., Boehnke, M., Lin, X., 2011. Rare-variant association testing for sequencing data with the sequence kernel association test. Am. J. Hum. Genet. 89, 82-93.
    Wu, W., Ji, P., Zhao, F., 2020. CircAtlas: an integrated resource of one million highly accurate circular RNAs from 1070 vertebrate transcriptomes. Genome Biol. 21, 101.
    Xia, K., Shabalin, A.A., Huang, S., Madar, V., Zhou, Y.H., Wang, W., Zou, F., Sun, W., Sullivan, P.F., Wright, F.A., 2012. seeQTL: a searchable database for human eQTLs. Bioinformatics 28, 451-452.
    Xia, S., Feng, J., Chen, K., Ma, Y., Gong, J., Cai, F., Jin, Y., Gao, Y., Xia, L., Chang, H., et al., 2018. CSCD: a database for cancer-specific circular RNAs. Nucleic Acids Res. 46, D925-D929.
    Xie, F., Liu, S., Wang, J., Xuan, J., Zhang, X., Qu, L., Zheng, L., Yang, J., 2021. deepBase v3.0: expression atlas and interactive analysis of ncRNAs from thousands of deep-sequencing data. Nucleic Acids Res. 49, D877-D883.
    Yang, Y., Muzny, D.M., Xia, F., Niu, Z., Person, R., Ding, Y., Ward, P., Braxton, A., Wang, M., Buhay, C., et al., 2014. Molecular findings among patients referred for clinical whole-exome sequencing. JAMA 312, 1870-1879.
    Zeng, W., Chen, S., Cui, X., Chen, X., Gao, Z., Jiang, R., 2021. SilencerDB: a comprehensive database of silencers. Nucleic Acids Res. 49, D221-D228.
    Zeng, W., Min, X., Jiang, R., 2019. EnDisease: a manually curated database for enhancer-disease associations. Database (Oxford) 2019, baz020.
    Zhang, G., Shi, J., Zhu, S., Lan, Y., Xu, L., Yuan, H., Liao, G., Liu, X., Zhang, Y., Xiao, Y., Li, X., 2018. DiseaseEnhancer: a resource of human disease-associated enhancer catalog. Nucleic Acids Res. 46, D78-D84.
    Zhao, H., Sun, Z., Wang, J., Huang, H., Kocher, J.P., Wang, L., 2014. CrossMap: a versatile tool for coordinate conversion between genome assemblies. Bioinformatics 30, 1006-1007.
    Zhao, Y., Li, H., Fang, S., Kang, Y., Wu, W., Hao, Y., Li, Z., Bu, D., Sun, N., Zhang, M.Q., Chen, R., 2016. NONCODE 2016: an informative and valuable data source of long non-coding RNAs. Nucleic Acids Res. 44, D203-D208.
    Zhou, H., Arapoglou, T., Li, X., Li, Z., Zheng, X., Moore, J., Asok, A., Kumar, S., Blue, E.E., Buyske, S., et al., 2023. FAVOR: functional annotation of variants online resource and annotator for variation across the human genome. Nucleic Acids Res. 51, D1300-D1311.
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