{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,9]],"date-time":"2026-02-09T03:58:18Z","timestamp":1770609498589,"version":"3.49.0"},"reference-count":17,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T00:00:00Z","timestamp":1748563200000},"content-version":"vor","delay-in-days":62,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100022018","name":"GENESIS","doi-asserted-by":"crossref","id":[{"id":"10.13039\/100022018","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100001665","name":"Agence Nationale de la Recherche","doi-asserted-by":"publisher","award":["ANR-21-CE14-0051"],"award-info":[{"award-number":["ANR-21-CE14-0051"]}],"id":[{"id":"10.13039\/501100001665","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,3,29]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>High concentration of lipoprotein(a) [Lp(a)], a lipoprotein with proatherogenic properties, is an important risk factor for cardiovascular disease. This concentration is mostly genetically determined by a complex interplay between the number of kringle\u00a0IV type 2 repeats and Lp(a)-affecting\u00a0variants. Besides Lp(a) plasma concentration, there is an unmet need to identify individuals most at risk based on their LPA genotype. We developed KILDA (KIv2 Length Determined from a kmer Analysis), a Nextflow pipeline, to identify the number of kringle\u00a0IV type 2 repeats and Lp(a)-affecting variants directly from kmers generated from FASTQ files. The pipeline was tested on the 1000 Genomes Project (n\u00a0=\u00a02459) and results were equivalent to DRAGEN-LPA (R2=\u00a00.92). In\u00a0silico datasets proved the robustness of KILDA\u2019s predictions under different scenarios of sequencing coverage and quality. In brief, KILDA is a robust, open-source, and free-to-use pipeline that can identify the number of kringle\u00a0IV type 2 repeats and Lp(a)-associated variants even when inputting low-coverage libraries.<\/jats:p>","DOI":"10.1093\/nargab\/lqaf070","type":"journal-article","created":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T10:05:48Z","timestamp":1748599548000},"source":"Crossref","is-referenced-by-count":1,"title":["KILDA: identifying KIV-2 repeats from kmers"],"prefix":"10.1093","volume":"7","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2569-6764","authenticated-orcid":false,"given":"Corentin","family":"Molitor","sequence":"first","affiliation":[{"name":"Plateforme NGS-HCL, Cellule bioinformatique, Service de g\u00e9n\u00e9tique, Hospices Civils de Lyon , 69000, Bron ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Timothy","family":"Labidi","sequence":"additional","affiliation":[{"name":"Plateforme NGS-HCL, Cellule bioinformatique, Service de g\u00e9n\u00e9tique, Hospices Civils de Lyon , 69000, Bron ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2971-4926","authenticated-orcid":false,"given":"Antoine","family":"Rimbert","sequence":"additional","affiliation":[{"name":"Nantes Universit , 44000, Nantes ,","place":["France"]},{"name":"\u00e9, CNRS, CHU Nantes, Inserm, l\u2019institut du thorax , 44000, Nantes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1580-8040","authenticated-orcid":false,"given":"Bertrand","family":"Cariou","sequence":"additional","affiliation":[{"name":"Nantes Universit , 44000, Nantes ,","place":["France"]},{"name":"\u00e9, CNRS, CHU Nantes, Inserm, l\u2019institut du thorax , 44000, Nantes ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6206-5908","authenticated-orcid":false,"given":"Mathilde","family":"Di\u00a0Filippo","sequence":"additional","affiliation":[{"name":"Service de Biochimie et Biologie Mol\u00e9culaire, Laboratoire de Biologie M\u00e9dicale MultiSites, Hospices Civils de Lyon , 69000, Bron ,","place":["France"]},{"name":"CarMen Laboratory, INSERM, INRAE, U , 69500, Pierre-B\u00e9nite,","place":["France"]},{"name":"niversit\u00e9 Claude Bernard Lyon 1 , 69500, Pierre-B\u00e9nite,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0001-7197-8730","authenticated-orcid":false,"given":"Claire","family":"Bardel","sequence":"additional","affiliation":[{"name":"Plateforme NGS-HCL, Cellule bioinformatique, Service de g\u00e9n\u00e9tique, Hospices Civils de Lyon , 69000, Bron ,","place":["France"]},{"name":"Universite Claude Bernard Lyon , 69100, Villeurbanne ,","place":["France"]},{"name":"1, LBBE, UMR 5558, CNRS , 69100, Villeurbanne ,","place":["France"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,5,30]]},"reference":[{"key":"2025053006054430500_B1","doi-asserted-by":"publisher","first-page":"e93","DOI":"10.1161\/CIR.0000000000001123","article-title":"Heart disease and stroke statistics\u20142023 update: a report from the American Heart Association","volume":"147","author":"Tsao","year":"2023","journal-title":"Circulation"},{"key":"2025053006054430500_B2","doi-asserted-by":"publisher","first-page":"465","DOI":"10.1161\/ATVBAHA.120.315291","article-title":"Lp(a) (lipoprotein[a]) concentrations and incident atherosclerotic cardiovascular disease","volume":"41","author":"Patel","year":"2021","journal-title":"Arterioscler Thromb Vasc Biol"},{"key":"2025053006054430500_B3","doi-asserted-by":"publisher","first-page":"3925","DOI":"10.1093\/eurheartj\/ehac361","article-title":"Lipoprotein(a) in atherosclerotic cardiovascular disease and aortic stenosis: a European Atherosclerosis Society consensus statement","volume":"43","author":"Kronenberg","year":"2022","journal-title":"Eur Heart J"},{"key":"2025053006054430500_B4","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.atherosclerosis.2022.04.003","article-title":"Lipoprotein(a) beyond the kringle IV repeat polymorphism: the complexity of genetic variation in the LPA gene","volume":"349","author":"Coassin","year":"2022","journal-title":"Atherosclerosis"},{"key":"2025053006054430500_B5","doi-asserted-by":"publisher","first-page":"1339","DOI":"10.1194\/jlr.R067314","article-title":"Structure, function, and genetics of lipoprotein(a)","volume":"57","author":"Schmidt","year":"2016","journal-title":"J Lipid Res"},{"key":"2025053006054430500_B6","doi-asserted-by":"publisher","first-page":"828","DOI":"10.1016\/j.acvd.2021.10.009","article-title":"Lipoprotein(a): pathophysiology, measurement, indication and treatment in cardiovascular disease. A consensus statement from the Nouvelle Soci\u00e9t\u00e9 Francophone d\u2019Ath\u00e9roscl\u00e9rose (NSFA)","volume":"114","author":"Durlach","year":"2021","journal-title":"Arch Cardiovasc Dis"},{"key":"2025053006054430500_B7","doi-asserted-by":"publisher","first-page":"499","DOI":"10.1093\/clinchem\/18.6.499","article-title":"Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge","volume":"18","author":"Friedewald","year":"1972","journal-title":"Clin Chem"},{"key":"2025053006054430500_B8","doi-asserted-by":"publisher","first-page":"100053","DOI":"10.1016\/j.jlr.2021.100053","article-title":"Novel method for quantification of lipoprotein(a)-cholesterol: implications for improving accuracy of LDL-C measurements","volume":"62","author":"Yeang","year":"2021","journal-title":"J Lipid Res"},{"key":"2025053006054430500_B9","doi-asserted-by":"publisher","first-page":"27","DOI":"10.1016\/j.atherosclerosis.2022.11.020","article-title":"Use of lipoprotein(a) to improve diagnosis and management in clinical familial hypercholesterolemia","volume":"365","author":"Tromp","year":"2023","journal-title":"Atherosclerosis"},{"key":"2025053006054430500_B10","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1016\/S0140-6736(24)01308-4","article-title":"Lipoprotein(a) and cardiovascular disease","volume":"404","author":"Nordestgaard","year":"2024","journal-title":"Lancet"},{"key":"2025053006054430500_B11","doi-asserted-by":"publisher","first-page":"1255","DOI":"10.1161\/CIRCGEN.120.003182","article-title":"Genetic predictor to identify individuals with high lipoprotein(a) concentrations","volume":"14","author":"Dron","year":"2021","journal-title":"Circ Genom Precis Med"},{"key":"2025053006054430500_B12","doi-asserted-by":"publisher","first-page":"255","DOI":"10.1186\/s12920-024-02024-0","article-title":"Identification of allele-specific KIV-2 repeats and impact on Lp(a) measurements for cardiovascular disease risk","volume":"17","author":"Behera","year":"2024","journal-title":"BMC Med Genomics"},{"key":"2025053006054430500_B13","doi-asserted-by":"publisher","first-page":"764","DOI":"10.1093\/bioinformatics\/btr011","article-title":"A fast, lock-free approach for efficient parallel counting of occurrences of k-mers","volume":"27","author":"Mar\u00e7ais","year":"2011","journal-title":"Bioinformatics"},{"key":"2025053006054430500_B14","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1038\/nature15393","article-title":"A global reference for human genetic variation","volume":"526","author":"Auton","year":"2015","journal-title":"Nature"},{"key":"2025053006054430500_B15","doi-asserted-by":"publisher","first-page":"192","DOI":"10.1161\/CIRCULATIONAHA.123.066398","article-title":"Relating lipoprotein(a) concentrations to cardiovascular event risk after acute coronary syndrome: a comparison of 3 tests","volume":"149","author":"Szarek","year":"2024","journal-title":"Circulation"},{"key":"2025053006054430500_B16","doi-asserted-by":"publisher","first-page":"167","DOI":"10.1186\/s13059-024-03316-5","article-title":"Resolving intra-repeat variation in medically relevant VNTRs from short-read sequencing data using the cardiovascular risk gene LPA as a model","volume":"25","author":"Di","year":"2024","journal-title":"Genome Biol"},{"key":"2025053006054430500_B17","doi-asserted-by":"publisher","first-page":"117","DOI":"10.1186\/s13073-024-01391-8","article-title":"Nanopore sequencing with unique molecular identifiers enables accurate mutation analysis and haplotyping in the complex lipoprotein(a) KIV-2 VNTR","volume":"16","author":"Amstler","year":"2024","journal-title":"Genome Med"}],"container-title":["NAR Genomics and Bioinformatics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/nargab\/article-pdf\/7\/2\/lqaf070\/63404670\/lqaf070.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/nargab\/article-pdf\/7\/2\/lqaf070\/63404670\/lqaf070.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,5,30]],"date-time":"2025-05-30T10:05:50Z","timestamp":1748599550000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/nargab\/article\/doi\/10.1093\/nargab\/lqaf070\/8153604"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,29]]},"references-count":17,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2025,3,29]]}},"URL":"https:\/\/doi.org\/10.1093\/nargab\/lqaf070","relation":{},"ISSN":["2631-9268"],"issn-type":[{"value":"2631-9268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,3,29]]},"article-number":"lqaf070"}}