{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:27:55Z","timestamp":1768570075279,"version":"3.49.0"},"posted":{"date-parts":[[2025,3,13]]},"group-title":"Genetic and Genomic Medicine","reference-count":46,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T00:00:00Z","timestamp":1741824000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.medrxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,3,13]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                <jats:sec>\n                  <jats:title>Introduction<\/jats:title>\n                  <jats:p>The use of next-generation sequencing technologies (NGS) to study parasite populations and their response and evolution to interventions is important to support malaria control and elimination efforts. While whole genome sequencing (WGS) is optimal in terms of assessing the entire genome, it is costly for numerous samples. Targeted approaches selectively enriching for sequence of interest are more affordable but sometimes lack adequate information content for key analyses.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Methods<\/jats:title>\n                  <jats:p>\n                    We have developed a highly-multiplexed molecular inversion probe (MIP) panel (IBC2FULL) targeting single nucleotide polymorphisms (SNPs) with \u2265 5% minor allele frequency (MAF) in sub-Saharan African regions from publicly available\n                    <jats:italic>Plasmodium falciparum<\/jats:italic>\n                    WGS. We optimized the panel alone and in combination with antimalarial drug resistance MIPs in laboratory\n                    <jats:italic>P. falciparum<\/jats:italic>\n                    strains at different parasitemias, and validated it by sequencing field isolates from Democratic Republic of Congo, Ethiopia, Ghana, Mali, Rwanda, Tanzania and Uganda and evaluating population structure, identity-by-descent (IBD), signals of selection, and complexity of infection (COI)\n                  <\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Results<\/jats:title>\n                  <jats:p>The new panel IBC2FULL consisted of 2,128 MIP microhaplotypes (containing 4,264 common SNPs) spaced by 5.1 - 18.4 kb across the entire genome. While these microhaplotypes were developed based on variation from sub-Saharan African WGS, 59.3% (2,529) of SNPs were also common in South-East Asia. The MIPs were balanced to produce more uniform and higher depth coverage at low parasitemia (100 parasites\/\u03bcL) along with MIPs targeting antimalarial drug resistance genes. Comparing targeted regions extracted from public WGS, IBC2FULL provided higher resolution of local population structure in sub-Saharan Africa than current PCR-based targeted sequencing panels. Sequencing field samples, IBC2FULL approximated WGS measures of relatedness, population structure, and COI. Interestingly, genome-wide analysis of extended haplotype homozygosity detected the same major peaks of selection as WGS. We also chose a subset of 305 high performing probes to create a core panel (IBC2CORE) that produced high-quality data for basic population genomic analysis and accurate estimation of COI.<\/jats:p>\n                <\/jats:sec>\n                <jats:sec>\n                  <jats:title>Discussion<\/jats:title>\n                  <jats:p>IBC2FULL and IBC2CORE provide an improved platform for malaria genomic epidemiology and biology that can approximate WGS for many applications and is deployable for malaria molecular surveillance in resource-limited settings.<\/jats:p>\n                <\/jats:sec>","DOI":"10.1101\/2025.03.07.25323597","type":"posted-content","created":{"date-parts":[[2025,3,13]],"date-time":"2025-03-13T16:30:16Z","timestamp":1741883416000},"source":"Crossref","is-referenced-by-count":2,"title":["Highly multiplex molecular inversion probe panel in Plasmodium falciparum targeting common SNPs approximates whole genome sequencing assessments for selection and relatedness"],"prefix":"10.64898","author":[{"given":"Karamoko","family":"Niar\u00e9","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Crudale","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Abebe A.","family":"Fola","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Neeva","family":"Wernsman Young","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Victor","family":"Asua","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9984-8030","authenticated-orcid":false,"given":"Melissa","family":"Conrad","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pierre","family":"Gashema","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anita","family":"Ghansah","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stan","family":"Hangi","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Deus S.","family":"Ishengoma","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jean-Baptiste","family":"Mazarati","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayalew Jejaw","family":"Zeleke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philip J.","family":"Rosenthal","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0062-2283","authenticated-orcid":false,"given":"Abdoulaye A.","family":"Djimd\u00e9","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jonathan J.","family":"Juliano","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey A","family":"Bailey","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"issue":"7","key":"2025032002490537000_2025.03.07.25323597v1.1","doi-asserted-by":"crossref","first-page":"1213","DOI":"10.1038\/s41564-023-01377-z","article-title":"Chloroquine resistance evolution in Plasmodium falciparum is mediated by the putative amino acid transporter AAT1","volume":"8","year":"2023","journal-title":"Nature Microbiology"},{"key":"2025032002490537000_2025.03.07.25323597v1.2","doi-asserted-by":"publisher","DOI":"10.1093\/molbev\/mss151"},{"key":"2025032002490537000_2025.03.07.25323597v1.3","doi-asserted-by":"publisher","DOI":"10.1101\/2024.08.22.609145"},{"key":"2025032002490537000_2025.03.07.25323597v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nature12876"},{"key":"2025032002490537000_2025.03.07.25323597v1.5","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1314981"},{"key":"2025032002490537000_2025.03.07.25323597v1.6","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiy223"},{"issue":"1","key":"2025032002490537000_2025.03.07.25323597v1.7","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1186\/s13071-020-3904-y","article-title":"Geographical distribution of Anopheles stephensi in eastern Ethiopia","volume":"13","year":"2020","journal-title":"Parasites & Vectors"},{"key":"2025032002490537000_2025.03.07.25323597v1.8","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4939-6442-0_6"},{"issue":"1","key":"2025032002490537000_2025.03.07.25323597v1.9","doi-asserted-by":"crossref","first-page":"e1005348","DOI":"10.1371\/journal.pcbi.1005348","article-title":"THE REAL McCOIL: A method for the concurrent estimation of the complexity of infection and SNP allele frequency for malaria parasites","volume":"13","year":"2017","journal-title":"PLoS Computational Biology"},{"key":"2025032002490537000_2025.03.07.25323597v1.10","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2211803)"},{"key":"2025032002490537000_2025.03.07.25323597v1.11","doi-asserted-by":"crossref","first-page":"943445","DOI":"10.3389\/fgene.2022.943445","article-title":"Genome-wide SNP analysis of Plasmodium falciparum shows differentiation at drug-resistance-associated loci among malaria transmission settings in southern Mali","volume":"13","year":"2022","journal-title":"Frontiers in Genetics"},{"issue":"1","key":"2025032002490537000_2025.03.07.25323597v1.12","doi-asserted-by":"crossref","first-page":"619","DOI":"10.1038\/s42003-023-04997-7","article-title":"Targeted and whole-genome sequencing reveal a north-south divide in P. falciparum drug resistance markers and genetic structure in Mozambique","volume":"6","year":"2023","journal-title":"Communications Biology"},{"key":"2025032002490537000_2025.03.07.25323597v1.13","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0808859"},{"issue":"10","key":"2025032002490537000_2025.03.07.25323597v1.14","doi-asserted-by":"crossref","first-page":"1911","DOI":"10.1038\/s41564-023-01461-4","article-title":"Plasmodium falciparum resistant to artemisinin and diagnostics have emerged in Ethiopia","volume":"8","year":"2023","journal-title":"Nature Microbiology"},{"key":"2025032002490537000_2025.03.07.25323597v1.15","unstructured":"Garrison, E. , & Marth, G. (2012). Haplotype-based variant detection from short-read sequencing. In arXiv [q-bio.GN]. arXiv. http:\/\/arxiv.org\/abs\/1207.3907"},{"key":"2025032002490537000_2025.03.07.25323597v1.16","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/bts115"},{"key":"2025032002490537000_2025.03.07.25323597v1.17","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkx1201"},{"key":"2025032002490537000_2025.03.07.25323597v1.18","doi-asserted-by":"publisher","DOI":"10.1101\/2024.01.31.24301954"},{"key":"2025032002490537000_2025.03.07.25323597v1.19","doi-asserted-by":"publisher","DOI":"10.7554\/eLife.62997"},{"key":"2025032002490537000_2025.03.07.25323597v1.20","doi-asserted-by":"publisher","DOI":"10.1101\/2023.11.07.23298207"},{"key":"2025032002490537000_2025.03.07.25323597v1.21","doi-asserted-by":"publisher","DOI":"10.1111\/1755-0998.13622"},{"key":"2025032002490537000_2025.03.07.25323597v1.22","doi-asserted-by":"crossref","first-page":"42","DOI":"10.12688\/wellcomeopenres.16168.1","article-title":"An open dataset of Plasmodium falciparum genome variation in 7,000 worldwide samples","volume":"6","author":"MalariaGEN","year":"2021","journal-title":"Wellcome Open Research"},{"key":"2025032002490537000_2025.03.07.25323597v1.23","doi-asserted-by":"publisher","DOI":"10.1038\/nature11174"},{"key":"2025032002490537000_2025.03.07.25323597v1.24","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2210956"},{"key":"2025032002490537000_2025.03.07.25323597v1.25","doi-asserted-by":"publisher","DOI":"10.1101\/gr.203711.115"},{"key":"2025032002490537000_2025.03.07.25323597v1.26","doi-asserted-by":"publisher","DOI":"10.1111\/mec.15706"},{"key":"2025032002490537000_2025.03.07.25323597v1.27","doi-asserted-by":"publisher","DOI":"10.1038\/ng.528"},{"key":"2025032002490537000_2025.03.07.25323597v1.28","doi-asserted-by":"publisher","DOI":"10.1186\/gb-2008-9-12-r171"},{"key":"2025032002490537000_2025.03.07.25323597v1.29","doi-asserted-by":"publisher","DOI":"10.1038\/s41576-021-00349-5"},{"issue":"1","key":"2025032002490537000_2025.03.07.25323597v1.30","doi-asserted-by":"crossref","first-page":"236","DOI":"10.1186\/s12936-017-1886-9","article-title":"Surveillance for sulfadoxine-pyrimethamine resistant malaria parasites in the Lake and Southern Zones, Tanzania, using pooling and next-generation sequencing","volume":"16","year":"2017","journal-title":"Malaria Journal"},{"issue":"1","key":"2025032002490537000_2025.03.07.25323597v1.31","doi-asserted-by":"crossref","first-page":"207","DOI":"10.1186\/s12936-023-04632-0","article-title":"An optimized GATK4 pipeline for Plasmodium falciparum whole genome sequencing variant calling and analysis","volume":"22","year":"2023","journal-title":"Malaria Journal"},{"key":"2025032002490537000_2025.03.07.25323597v1.32","doi-asserted-by":"publisher","DOI":"10.1101\/2022.05.26.493561"},{"key":"2025032002490537000_2025.03.07.25323597v1.33","doi-asserted-by":"publisher","DOI":"10.1016\/j.pt.2015.11.010"},{"key":"2025032002490537000_2025.03.07.25323597v1.34","doi-asserted-by":"publisher","DOI":"10.1128\/JCM.00235-16"},{"issue":"7","key":"2025032002490537000_2025.03.07.25323597v1.35","doi-asserted-by":"crossref","first-page":"e1001685","DOI":"10.1371\/journal.pmed.1001685","article-title":"Efficacy and Safety of the RTS,S\/AS01 Malaria Vaccine during 18 Months after Vaccination: A Phase 3 Randomized, Controlled Trial in Children and Young Infants at 11 African Sites","volume":"11","author":"RTSS Clinical Trials Partnership","year":"2014","journal-title":"PLoS Medicine"},{"issue":"9988","key":"2025032002490537000_2025.03.07.25323597v1.36","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1016\/S0140-6736(15)60721-8","article-title":"Efficacy and safety of RTS,S\/AS01 malaria vaccine with or without a booster dose in infants and children in Africa: final results of a phase 3, individually randomised, controlled trial","volume":"386","author":"RTS,S Clinical Trials Partnership","year":"2015","journal-title":"The Lancet"},{"key":"2025032002490537000_2025.03.07.25323597v1.37","doi-asserted-by":"publisher","DOI":"10.1101\/2024.10.03.24314715"},{"issue":"1","key":"2025032002490537000_2025.03.07.25323597v1.38","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1186\/s12936-018-2349-7","article-title":"hmmIBD: software to infer pairwise identity by descent between haploid genotypes","volume":"17","year":"2018","journal-title":"Malaria Journal"},{"issue":"3","key":"2025032002490537000_2025.03.07.25323597v1.39","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1007\/s00436-019-06213-0","article-title":"Five years following first detection of Anopheles stephensi (Diptera: Culicidae) in Djibouti, Horn of Africa: populations established-malaria emerging","volume":"118","year":"2019","journal-title":"Parasitology Research"},{"key":"2025032002490537000_2025.03.07.25323597v1.40","doi-asserted-by":"publisher","DOI":"10.1093\/infdis\/jiaa527"},{"key":"2025032002490537000_2025.03.07.25323597v1.41","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-020-1005-2"},{"issue":"4","key":"2025032002490537000_2025.03.07.25323597v1.42","doi-asserted-by":"crossref","first-page":"e1001383","DOI":"10.1371\/journal.pgen.1001383","article-title":"Identification and functional validation of the novel antimalarial resistance locus PF10_0355 in Plasmodium falciparum","volume":"7","year":"2011","journal-title":"PLoS Genetics"},{"issue":"1","key":"2025032002490537000_2025.03.07.25323597v1.43","doi-asserted-by":"crossref","first-page":"2107","DOI":"10.1038\/s41467-020-15779-8","article-title":"The impact of antimalarial resistance on the genetic structure of Plasmodium falciparum in the DRC","volume":"11","year":"2020","journal-title":"Nature Communications"},{"key":"2025032002490537000_2025.03.07.25323597v1.44","doi-asserted-by":"publisher","DOI":"10.1038\/nrg3187"},{"key":"2025032002490537000_2025.03.07.25323597v1.45","unstructured":"World Health Organization. (2023). World malaria report 2023. World Health Organization."},{"key":"2025032002490537000_2025.03.07.25323597v1.46","doi-asserted-by":"publisher","DOI":"10.1101\/2024.04.29.24306442"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2025.03.07.25323597","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T20:30:20Z","timestamp":1768509020000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2025.03.07.25323597"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,13]]},"references-count":46,"URL":"https:\/\/doi.org\/10.1101\/2025.03.07.25323597","relation":{"is-preprint-of":[{"id-type":"doi","id":"10.3389\/fgene.2025.1526049","asserted-by":"subject"}]},"subject":[],"published":{"date-parts":[[2025,3,13]]},"subtype":"preprint"}}