{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T13:09:03Z","timestamp":1788959343973,"version":"build-2803163510"},"reference-count":48,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T00:00:00Z","timestamp":1788480000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001321","name":"National Research Foundation of South Africa","doi-asserted-by":"publisher","award":["NFSG240503217275"],"award-info":[{"award-number":["NFSG240503217275"]}],"id":[{"id":"10.13039\/501100001321","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Closely related Aspergillus section Nigri species are difficult to resolve taxonomically, while short-read comparisons may be influenced by reference-genome choice. We applied reciprocal genome projection to 31 whole-genome sequencing libraries representing South African clinical section-Nigri isolates, Japanese and USA A. niger-labeled isolates, and A. welwitschiae-labeled isolates. Reads were aligned independently to A. niger ATCC 1015 and A. welwitschiae Aspwel1, followed by reference-specific differential-representation and KEGG analyses. Species-level classification showed substantial overlap between A. niger and A. welwitschiae. The A. welwitschiae\u2013South African comparison identified 44 and 59 effect-qualified features under the respective projections, including 20 reciprocal feature pairs defining a reference-robust A. welwitschiae-associated core. The clinical Japanese\u2013South African comparison identified 116 and 127 features, with 14 concordant KEGG orthologs involving sterol modification, protein prenylation, cofactor metabolism, redox processing, cell-wall turnover and ribosome maturation. No pathway remained significant after false discovery-rate correction; nominal pathway signals were reference-sensitive. Reciprocal projection, therefore, recovered localized cohort-associated genomic differentiation while identifying reference-conditioned effects. These findings represent differential genomic-read representation and do not independently establish copy-number variation, pathway activity, virulence or antifungal resistance.<\/jats:p>","DOI":"10.3390\/pathogens15090941","type":"journal-article","created":{"date-parts":[[2026,9,4]],"date-time":"2026-09-04T17:25:56Z","timestamp":1788542756000},"page":"941","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Reciprocal Genome Projection Reveals Reference-Conditioned Functional Variation in Clinical Aspergillus Section Nigri Isolates"],"prefix":"10.3390","volume":"15","author":[{"ORCID":"https:\/\/orcid.org\/0009-0000-3579-4558","authenticated-orcid":false,"given":"Siphiwengesihle Kuhle Silindile","family":"Mbamali","sequence":"first","affiliation":[{"name":"Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban 4001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"data-curation","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"visualization","vocabulary":"credit"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"software","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9532-3504","authenticated-orcid":false,"given":"Nikwando","family":"Mohlomi","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban 4001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"visualization","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"formal-analysis","vocabulary":"credit"},{"role":"investigation","vocabulary":"credit"},{"role":"methodology","vocabulary":"credit"},{"role":"writing-original-draft","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"given":"Magriet van der","family":"Nest","sequence":"additional","affiliation":[{"name":"Forestry and Agricultural Biotechnology Institute (FABI), Department of Biochemistry, Genetics and Microbiology, Faculty of Natural and Agricultural Sciences, University of Pretoria, Pretoria 0028, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"validation","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"}]},{"given":"Nokuthula Peace","family":"Mchunu","sequence":"additional","affiliation":[{"name":"School of Life Science, Westville, College of Agriculture, Engineering and Science, University of KwaZulu-Natal, Durban 4000, South Africa"},{"name":"National Research Foundation, Meiring Naude Road, Brummeria, Pretoria 0001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"conceptualization","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5032-3092","authenticated-orcid":false,"given":"Kugenthiren","family":"Permaul","sequence":"additional","affiliation":[{"name":"Department of Biotechnology and Food Science, Faculty of Applied Sciences, Durban University of Technology, Durban 4001, South Africa"}],"role":[{"vocabulary":"crossref","role":"author"},{"role":"funding-acquisition","vocabulary":"credit"},{"role":"project-administration","vocabulary":"credit"},{"role":"supervision","vocabulary":"credit"},{"role":"writing-review-editing","vocabulary":"credit"},{"role":"conceptualization","vocabulary":"credit"},{"role":"resources","vocabulary":"credit"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1688","DOI":"10.1038\/s41588-018-0246-1","article-title":"Investigation of inter-and intraspecies variation through genome sequencing of Aspergillus section Nigri","volume":"50","author":"Vesth","year":"2018","journal-title":"Nat. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/s13059-017-1151-0","article-title":"Comparative genomics reveals high biological diversity and specific adaptations in the industrially and medically important fungal genus Aspergillus","volume":"18","author":"Riley","year":"2017","journal-title":"Genome Biol."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"001480","DOI":"10.1099\/jmm.0.001480","article-title":"Molecular identification and antifungal susceptibility of clinically relevant and cryptic species of Aspergillus sections Flavi and Nigri","volume":"71","author":"Nargesi","year":"2022","journal-title":"J. Med. Microbiol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"95","DOI":"10.3114\/sim.2022.102.03","article-title":"Reducing the number of accepted species in Aspergillus series Nigri","volume":"102","author":"Bian","year":"2022","journal-title":"Stud. Mycol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"e03980-23","DOI":"10.1128\/spectrum.03980-23","article-title":"Phylogenomics reveals extensive misidentification of fungal strains from the genus Aspergillus","volume":"12","author":"Balamurugan","year":"2024","journal-title":"Microbiol. Spectr."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"jkac124","DOI":"10.1093\/g3journal\/jkac124","article-title":"Genome sequences of 24 Aspergillus niger sensu stricto strains to study strain diversity, heterokaryon compatibility, and sexual reproduction","volume":"12","author":"Seekles","year":"2022","journal-title":"G3"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"i361","DOI":"10.1093\/bioinformatics\/btt215","article-title":"Short read alignment with populations of genomes","volume":"29","author":"Huang","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Naicker, S., Mohanlall, V., Ngubane, S., Mellem, J., and McHunu, N.P. (2023). Phenotypic array for identification and screening of antifungals against Aspergillus isolates from respiratory infections in KwaZulu Natal, South Africa. J. Fungi, 9.","DOI":"10.3390\/jof9060616"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"e2543630","DOI":"10.1001\/jamanetworkopen.2025.43630","article-title":"Triazole Resistance and Misidentification of Aspergillus tubingensis in Southern California","volume":"8","author":"Wang","year":"2025","journal-title":"JAMA Netw. Open"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"110517","DOI":"10.1016\/j.ygeno.2022.110517","article-title":"Phylogenomics and gene selection in Aspergillus welwitschiae: Possible implications in the pathogenicity in Agave sisalana","volume":"114","author":"Marone","year":"2022","journal-title":"Genomics"},{"key":"ref_11","unstructured":"Andrews, S. (2010). FastQC: A Quality Control Tool for High Throughput Sequence Data, Babraham Bioinformatics."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"gix029","DOI":"10.1093\/gigascience\/gix029","article-title":"Calculating the quality of public high-throughput sequencing data to obtain a suitable subset for reanalysis from the Sequence Read Archive","volume":"6","author":"Ohta","year":"2017","journal-title":"GigaScience"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3047","DOI":"10.1093\/bioinformatics\/btw354","article-title":"MultiQC: Summarize analysis results for multiple tools and samples in a single report","volume":"32","author":"Ewels","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"2114","DOI":"10.1093\/bioinformatics\/btu170","article-title":"Trimmomatic: A flexible trimmer for Illumina sequence data","volume":"30","author":"Bolger","year":"2014","journal-title":"Bioinformatics"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1038\/nbt.4163","article-title":"KBase: The United States department of energy systems biology knowledgebase","volume":"36","author":"Arkin","year":"2018","journal-title":"Nat. Biotechnol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"11257","DOI":"10.1038\/ncomms11257","article-title":"Fast and sensitive taxonomic classification for metagenomics with Kaiju","volume":"7","author":"Menzel","year":"2016","journal-title":"Nat. Commun."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"885","DOI":"10.1101\/gr.112169.110","article-title":"Comparative genomics of citric-acid-producing Aspergillus niger ATCC 1015 versus enzyme-producing CBS 513.88","volume":"21","author":"Andersen","year":"2011","journal-title":"Genome Res."},{"key":"ref_18","unstructured":"Li, H. (2013). Aligning sequence reads, clone sequences and assembly contigs with BWA-MEM. arXiv."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"giab008","DOI":"10.1093\/gigascience\/giab008","article-title":"Twelve years of SAMtools and BCFtools","volume":"10","author":"Danecek","year":"2021","journal-title":"GigaScience"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1093\/bioinformatics\/btv566","article-title":"Qualimap 2: Advanced multi-sample quality control for high-throughput sequencing data","volume":"32","author":"Okonechnikov","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_21","doi-asserted-by":"crossref","unstructured":"Lawrence, M., Huber, W., Pag\u00e8s, H., Aboyoun, P., Carlson, M., Gentleman, R., Morgan, M.T., and Carey, V.J. (2013). Software for computing and annotating genomic ranges. PLoS Comput. Biol., 9.","DOI":"10.1371\/journal.pcbi.1003118"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1038\/nmeth.3252","article-title":"Orchestrating high-throughput genomic analysis with Bioconductor","volume":"12","author":"Huber","year":"2015","journal-title":"Nat. Methods"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"EdgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics"},{"key":"ref_24","first-page":"e000243","article-title":"Pan-genome analyses of model fungal species","volume":"5","author":"McCarthy","year":"2019","journal-title":"Microb. Genom."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"289","DOI":"10.1111\/j.2517-6161.1995.tb02031.x","article-title":"Controlling the false discovery rate: A practical and powerful approach to multiple testing","volume":"57","author":"Benjamini","year":"1995","journal-title":"J. R. Stat. Soc. Ser. B (Methodol.)"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"3420","DOI":"10.1093\/nar\/gkn176","article-title":"High-throughput functional annotation and data mining with the Blast2GO suite","volume":"36","author":"Terol","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"5825","DOI":"10.1093\/molbev\/msab293","article-title":"EggNOG-mapper v2: Functional annotation, orthology assignments, and domain prediction at the metagenomic scale","volume":"38","author":"Cantalapiedra","year":"2021","journal-title":"Mol. Biol. Evol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1093\/nar\/28.1.27","article-title":"KEGG: Kyoto encyclopedia of genes and genomes","volume":"28","author":"Kanehisa","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_29","unstructured":"BioBam Bioinformatics (2026). Combined Pathway Analysis. OmicsBox User Manual, BioBam Bioinformatics."},{"key":"ref_30","unstructured":"BioBam Bioinformatics (2026). Gene Set Enrichment Analysis. OmicsBox User Manual, BioBam Bioinformatics."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"15545","DOI":"10.1073\/pnas.0506580102","article-title":"Gene set enrichment analysis: A knowledge-based approach for interpreting genome-wide expression profiles","volume":"102","author":"Subramanian","year":"2005","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"55411","DOI":"10.1074\/jbc.M406876200","article-title":"Rea1, a dynein-related nuclear AAA-ATPase, is involved in late rRNA processing and nuclear export of 60 S subunits","volume":"279","author":"Galani","year":"2004","journal-title":"J. Biol. Chem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"9547","DOI":"10.1016\/S0021-9258(18)60566-6","article-title":"The aldo-keto reductase superfamily: CDNAs and deduced amino acid sequences of human aldehyde and aldose reductases","volume":"264","author":"Bohren","year":"1989","journal-title":"J. Biol. Chem."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"24458","DOI":"10.1074\/jbc.271.40.24458","article-title":"Mitochondrial and cytosolic branched-chain amino acid transaminases from yeast, homologs of the myc oncogene-regulated Eca39 protein","volume":"271","author":"Kispal","year":"1996","journal-title":"J. Biol. Chem."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"4261","DOI":"10.1038\/s41467-024-48767-3","article-title":"The sterol C-24 methyltransferase encoding gene, erg6, is essential for viability of Aspergillus species","volume":"15","author":"Xie","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"681","DOI":"10.1007\/s11745-008-3198-x","article-title":"Photoaffinity labeling and mutational analysis of 24-C-sterol methyltransferase defines the AdoMet binding site","volume":"43","author":"Jayasimha","year":"2008","journal-title":"Lipids"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1016\/j.abb.2010.10.008","article-title":"Purification, characterization and inhibition of sterol C24-methyltransferase from Candida albicans","volume":"505","author":"Ganapathy","year":"2011","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_38","first-page":"1438","article-title":"Nucleotide sequence of the yeast STE14 gene, which encodes farnesylcysteine carboxyl methyltransferase, and demonstration of its essential role in a-factor export","volume":"14","author":"Sapperstein","year":"1994","journal-title":"Mol. Cell. Biol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4106","DOI":"10.1091\/mbc.e06-11-1006","article-title":"Isoprenylcysteine carboxy methylation is essential for development in Dictyostelium discoideum","volume":"18","author":"Chen","year":"2007","journal-title":"Mol. Biol. Cell"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"2714","DOI":"10.1105\/tpc.107.053389","article-title":"Isoprenylcysteine methylation and demethylation regulate abscisic acid signaling in Arabidopsis","volume":"20","author":"Huizinga","year":"2008","journal-title":"Plant Cell"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"7112","DOI":"10.1128\/jb.174.22.7112-7120.1992","article-title":"Phenol hydroxylase from Trichosporon cutaneum: Gene cloning, sequence analysis, and functional expression in Escherichia coli","volume":"174","author":"Neujahr","year":"1992","journal-title":"J. Bacteriol."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"1455","DOI":"10.1110\/ps.0356203","article-title":"Structure and properties of recombinant human pyridoxine 5\u2032-phosphate oxidase","volume":"12","author":"Musayev","year":"2003","journal-title":"Protein Sci."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"599","DOI":"10.1107\/S0907444905005512","article-title":"Structure of Escherichia coli pyridoxine 5\u2032-phosphate oxidase in a tetragonal crystal form: Insights into the mechanistic pathway of the enzyme","volume":"61","author":"Safo","year":"2005","journal-title":"Biol. Crystallogr."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"9132","DOI":"10.1073\/pnas.92.20.9132","article-title":"Fungal metabolic model for human type I hereditary tyrosinaemia","volume":"92","year":"1995","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"2929","DOI":"10.1099\/00221287-146-11-2929","article-title":"The Bacillus subtilis 168 csn gene encodes a chitosanase with similar properties to a Streptomyces enzyme","volume":"146","author":"Rivas","year":"2000","journal-title":"Microbiology"},{"key":"ref_46","doi-asserted-by":"crossref","unstructured":"Qi, G., Hao, L., Gan, Y., Xin, T., Lou, Q., Xu, W., and Song, J. (2024). Identification of closely related species in Aspergillus through Analysis of Whole-Genome. Front. Microbiol., 15.","DOI":"10.3389\/fmicb.2024.1323572"},{"key":"ref_47","doi-asserted-by":"crossref","unstructured":"Lofgren, L.A., Ross, B.S., Cramer, R.A., and Stajich, J.E. (2022). The pan-genome of Aspergillus fumigatus provides a high-resolution view of its population structure revealing high levels of lineage-specific diversity driven by recombination. PLoS Biol., 20.","DOI":"10.1371\/journal.pbio.3001890"},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Kappel, L., M\u00fcnsterk\u00f6tter, M., Sipos, G., Escobar Rodriguez, C., and Gruber, S. (2020). Chitin and chitosan remodeling defines vegetative development and Trichoderma biocontrol. PLoS Pathog., 16.","DOI":"10.1371\/journal.ppat.1008320"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/9\/941\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T12:53:08Z","timestamp":1788958388000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/15\/9\/941"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,9,4]]},"references-count":48,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2026,9]]}},"alternative-id":["pathogens15090941"],"URL":"https:\/\/doi.org\/10.3390\/pathogens15090941","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,9,4]]}}}