{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,24]],"date-time":"2026-01-24T19:08:50Z","timestamp":1769281730454,"version":"3.49.0"},"reference-count":78,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T00:00:00Z","timestamp":1767744000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Minist\u00e9rio da Ci\u00eancia","award":["408717\/2022-0"],"award-info":[{"award-number":["408717\/2022-0"]}]},{"name":"Minist\u00e9rio da Ci\u00eancia","award":["312797\/2021-4"],"award-info":[{"award-number":["312797\/2021-4"]}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["408717\/2022-0"],"award-info":[{"award-number":["408717\/2022-0"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100003593","name":"Conselho Nacional de Desenvolvimento Cient\u00edfico e Tecnol\u00f3gico","doi-asserted-by":"crossref","award":["312797\/2021-4"],"award-info":[{"award-number":["312797\/2021-4"]}],"id":[{"id":"10.13039\/501100003593","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004933","name":"Instituto Nacional de Ci\u00eancia e Tecnologia","doi-asserted-by":"crossref","award":["405934\/2022-0"],"award-info":[{"award-number":["405934\/2022-0"]}],"id":[{"id":"10.13039\/501100004933","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100004263","name":"Funda\u00e7\u00e3o de Amparo \u00e0 Pesquisa do Estado do Rio Grande do Sul","doi-asserted-by":"crossref","award":["22\/2551-0000396-6"],"award-info":[{"award-number":["22\/2551-0000396-6"]}],"id":[{"id":"10.13039\/501100004263","id-type":"DOI","asserted-by":"crossref"}]},{"DOI":"10.13039\/501100002322","name":"Coordena\u00e7\u00e3o de Aperfei\u00e7oamento de Pessoal de N\u00edvel Superior","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002322","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Programa de Excel\u00eancia Acad\u00eamica","award":["88882.346632\/2019-01"],"award-info":[{"award-number":["88882.346632\/2019-01"]}]},{"name":"Programa de Excel\u00eancia Acad\u00eamica","award":["88887.595440\/2020-00"],"award-info":[{"award-number":["88887.595440\/2020-00"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Microorganisms"],"abstract":"<jats:p>Cryptococcus neoformans is a pathogenic yeast and the leading cause of cryptococcosis in humans. The calcium-calcineurin signaling pathway plays a central role in stress adaptation and virulence. To identify the uncharacterized regulators of fungal adaptation, we utilized an integrative systems biology approach, combining differential gene expression and network analysis using transcriptomic data from three key components of the calcium-calcineurin pathway (Cna1, Crz1, and Pmc1). Our workflow identified the CNAG_00522 gene product, which we designated tricalbin 1 (TCB1) due to its conserved calcium and lipid-binding C2 domains. TCB1 expression was found to be regulated by both Cna1 and Pmc1. Network analyses positioned Tcb1 as a bottleneck linking general stress response and cellular processes. Further molecular characterization confirmed that TCB1 expression is temperature and calcium-responsive. Functional studies of the tcb1\u0394 mutant revealed an enlarged capsule, increased GXM shedding, and enhanced viability under host-mimicking conditions. However, phenotypic screening demonstrated that the tcb1\u0394 mutant does not display sensitivity to cell wall or osmotic stressors, and TCB1 deletion did not attenuate virulence in the Tenebrio larval model. These findings suggest that TCB1 functions as a specialized regulator of fungal growth at 37 \u00b0C, capsule size, and GXM shedding. This study validates our integrative approach for guiding the identification of these complex regulators.<\/jats:p>","DOI":"10.3390\/microorganisms14010122","type":"journal-article","created":{"date-parts":[[2026,1,7]],"date-time":"2026-01-07T09:34:12Z","timestamp":1767778452000},"page":"122","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Integrative Transcriptomic and Systems Biology Analyses Identify TCB1 as a Calcium-Responsive Gene in Cryptococcus neoformans"],"prefix":"10.3390","volume":"14","author":[{"given":"Andrea Gomes","family":"Tavanti","sequence":"first","affiliation":[{"name":"Molecular Biology of Pathogens Laboratory, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"},{"name":"Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J\u00falia Catarina Vieira","family":"Reuwsaat","sequence":"additional","affiliation":[{"name":"Molecular Biology of Pathogens Laboratory, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9367-1043","authenticated-orcid":false,"given":"Heryk","family":"Motta","sequence":"additional","affiliation":[{"name":"Molecular Biology of Pathogens Laboratory, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eamim Daidr\u00ea","family":"Squizani","sequence":"additional","affiliation":[{"name":"Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rodrigo Silva Araujo","family":"Streit","sequence":"additional","affiliation":[{"name":"Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1320-6174","authenticated-orcid":false,"given":"Patr\u00edcia Aline Gr\u00f6hs","family":"Ferrareze","sequence":"additional","affiliation":[{"name":"Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8230-6702","authenticated-orcid":false,"given":"Matheus da Silva","family":"Camargo","sequence":"additional","affiliation":[{"name":"Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2825-8295","authenticated-orcid":false,"given":"Bruno Cesar","family":"Feltes","sequence":"additional","affiliation":[{"name":"Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"},{"name":"Laboratory of DNA Repair and Aging, Department of Biophysics, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marilene Henning","family":"Vainstein","sequence":"additional","affiliation":[{"name":"Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"},{"name":"Laboratory of Microorganisms of Medical and Biotechnological Importance, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"},{"name":"Department of Molecular Biology and Biotechnology, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2433-6903","authenticated-orcid":false,"given":"Charley Christian","family":"Staats","sequence":"additional","affiliation":[{"name":"Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"},{"name":"Department of Molecular Biology and Biotechnology, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"},{"name":"Laboratory of Molecular and Cellular Microbiology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3766-5869","authenticated-orcid":false,"given":"L\u00edvia","family":"Kmetzsch","sequence":"additional","affiliation":[{"name":"Molecular Biology of Pathogens Laboratory, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"},{"name":"Graduate Program in Cellular and Molecular Biology, Center of Biotechnology, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"},{"name":"Department of Molecular Biology and Biotechnology, Institute of Biosciences, Federal University of Rio Grande do Sul, Porto Alegre 91501-970, Brazil"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2026,1,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"e428","DOI":"10.1016\/S1473-3099(23)00692-8","article-title":"Global incidence and mortality of severe fungal disease","volume":"24","author":"Denning","year":"2024","journal-title":"Lancet Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"069","DOI":"10.1055\/s-0039-3400280","article-title":"Cryptococcosis","volume":"41","author":"Zavala","year":"2020","journal-title":"Semin. Respir. Crit. Care Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1748","DOI":"10.1016\/S1473-3099(22)00499-6","article-title":"The global burden of HIV-associated cryptococcal infection in adults in 2020: A modelling analysis","volume":"22","author":"Rajasingham","year":"2022","journal-title":"Lancet Infect. Dis."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"106","DOI":"10.1038\/nrmicro.2015.6","article-title":"Cryptococcus: From environmental saprophyte to global pathogen","volume":"14","author":"May","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Molloy, S.F., Chiller, T., Greene, G.S., Burry, J., Govender, N.P., Kanyama, C., Mfinanga, S., Lesikari, S., Mapoure, Y.N., and Kouanfack, C. (2017). Cryptococcal meningitis: A neglected NTD?. PLoS Negl. Trop. Dis., 11.","DOI":"10.1371\/journal.pntd.0005575"},{"key":"ref_6","unstructured":"(2022). WHO Fungal Priority Pathogens List to Guide Research, Development and Public Health Action, World Health Organization. Available online: https:\/\/www.who.int\/publications\/i\/item\/9789240060241."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1007\/s40475-015-0046-y","article-title":"Cryptococcal Meningitis: Diagnosis and Management Update","volume":"2","author":"Abassi","year":"2015","journal-title":"Curr. Trop. Med. Rep."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"62","DOI":"10.1038\/s41572-023-00472-z","article-title":"Cryptococcal meningitis","volume":"9","author":"Tugume","year":"2023","journal-title":"Nat. Rev. Dis. Prim."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1080\/21505594.2016.1201250","article-title":"Calcineurin in fungal virulence and drug resistance: Prospects for harnessing targeted inhibition of calcineurin for an antifungal therapeutic approach","volume":"8","author":"Juvvadi","year":"2017","journal-title":"Virulence"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"453","DOI":"10.1016\/j.chom.2019.08.004","article-title":"Calcium-Calmodulin-Calcineurin Signaling: A Globally Conserved Virulence Cascade in Eukaryotic Microbial Pathogens","volume":"26","author":"Park","year":"2019","journal-title":"Cell Host Microbe"},{"key":"ref_11","doi-asserted-by":"crossref","unstructured":"Wall, G., and Lopez-Ribot, J.L. (2020). Current Antimycotics, New Prospects, and Future Approaches to Antifungal Therapy. Antibiotics, 9.","DOI":"10.3390\/antibiotics9080445"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Denham, S., and Brown, J. (2018). Mechanisms of Pulmonary Escape and Dissemination by Cryptococcus neoformans. J. Fungi, 4.","DOI":"10.3390\/jof4010025"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.fbr.2012.02.004","article-title":"Aimless mutants of Cryptococcus neoformans: Failure to disseminate","volume":"26","author":"Griffiths","year":"2012","journal-title":"Fungal Biol. Rev."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"490","DOI":"10.1080\/21505594.2019.1614383","article-title":"Basic principles of the virulence of Cryptococcus","volume":"10","author":"Zaragoza","year":"2019","journal-title":"Virulence"},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Chow, E.W.L., Clancey, S.A., Billmyre, R.B., Averette, A.F., A Granek, J., Mieczkowski, P., E Cardenas, M., and Heitman, J. (2017). Elucidation of the calcineurin-Crz1 stress response transcriptional network in the human fungal pathogen Cryptococcus neoformans. PLoS Genet., 13.","DOI":"10.1371\/journal.pgen.1006667"},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Park, H.S., Chow, E.W.L., Fu, C., Soderblom, E.J., Moseley, M.A., Heitman, J., and E Cardenas, M. (2016). Calcineurin Targets Involved in Stress Survival and Fungal Virulence. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005873"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1128\/EC.00114-10","article-title":"The Vacuolar Ca2+ Exchanger Vcx1 Is Involved in Calcineurin-Dependent Ca2+ Tolerance and Virulence in Cryptococcus neoformans","volume":"9","author":"Kmetzsch","year":"2010","journal-title":"Eukaryot. Cell"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"4853","DOI":"10.1111\/febs.12458","article-title":"The calcium transporter Pmc1 provides Ca2+ tolerance and influences the progression of murine cryptococcal infection","volume":"280","author":"Kmetzsch","year":"2013","journal-title":"FEBS J."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e12803","DOI":"10.1111\/cmi.12803","article-title":"Cryptococcal dissemination to the central nervous system requires the vacuolar calcium transporter Pmc1","volume":"20","author":"Squizani","year":"2018","journal-title":"Cell. Microbiol."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1080\/21501203.2020.1785962","article-title":"Calcium signaling is involved in diverse cellular processes in fungi","volume":"12","author":"Roy","year":"2020","journal-title":"Mycology"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"3394","DOI":"10.1128\/IAI.01977-06","article-title":"Eca1, a Sarcoplasmic\/Endoplasmic Reticulum Ca2+ -ATPase, Is Involved in Stress Tolerance and Virulence in Cryptococcus neoformans","volume":"75","author":"Fan","year":"2007","journal-title":"Infect. Immun."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"1788","DOI":"10.1128\/EC.00158-06","article-title":"Cch1 Mediates Calcium Entry in Cryptococcus neoformans and Is Essential in Low-Calcium Environments","volume":"5","author":"Liu","year":"2006","journal-title":"Eukaryot. Cell"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Lev, S., Desmarini, D., Chayakulkeeree, M., Sorrell, T.C., and Djordjevic, J.T. (2012). The Crz1\/Sp1 Transcription Factor of Cryptococcus neoformans Is Activated by Calcineurin and Regulates Cell Wall Integrity. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0051403"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Yadav, V., and Heitman, J. (2023). Calcineurin: The Achilles\u2019 heel of fungal pathogens. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011445"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"540","DOI":"10.3724\/abbs.2023011","article-title":"Combating increased antifungal drug resistance in Cryptococcus, what should we do in the future?","volume":"55","author":"Deng","year":"2023","journal-title":"Acta Biochim. Biophys. Sin."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1038\/s41579-021-00511-0","article-title":"Treatment strategies for cryptococcal infection: Challenges, advances and future outlook","volume":"19","author":"Iyer","year":"2021","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"D991","DOI":"10.1093\/nar\/gks1193","article-title":"NCBI GEO: Archive for functional genomics data sets\u2014Update","volume":"41","author":"Barrett","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D19","DOI":"10.1093\/nar\/gkq1019","article-title":"The Sequence Read Archive","volume":"39","author":"Leinonen","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"D15","DOI":"10.1093\/nar\/gkq1150","article-title":"The International Nucleotide Sequence Database Collaboration","volume":"39","author":"Cochrane","year":"2011","journal-title":"Nucleic Acids Res."},{"key":"ref_30","unstructured":"Andrews, S. (2025, September 01). FastQC: A Quality Control Tool for High Throughput Sequence Data. Published Online. Available online: http:\/\/www.bioinformatics.babraham.ac.uk\/projects\/fastqc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"10","DOI":"10.14806\/ej.17.1.200","article-title":"Cutadapt removes adapter sequences from high-throughput sequencing reads","volume":"17","author":"Martin","year":"2011","journal-title":"EMBnet. J."},{"key":"ref_32","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_33","unstructured":"Joshi, N.A., and Fass, J.N. (2025, September 01). Sickle: A Sliding-Window, Adaptive, Quality-Based Trimming Tool for FastQ Files. Available online: https:\/\/github.com\/najoshi\/sickle."},{"key":"ref_34","unstructured":"Hannon, G.J. (2025, April 03). FASTX-Toolkit. Published Online 2010. Available online: http:\/\/hannonlab.cshl.edu\/fastx_toolkit."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1093\/bioinformatics\/bts635","article-title":"STAR: Ultrafast universal RNA-seq aligner","volume":"29","author":"Dobin","year":"2013","journal-title":"Bioinformatics"},{"key":"ref_36","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_37","doi-asserted-by":"crossref","first-page":"2078","DOI":"10.1093\/bioinformatics\/btp352","article-title":"The Sequence Alignment\/Map format and SAMtools","volume":"25","author":"Li","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"166","DOI":"10.1093\/bioinformatics\/btu638","article-title":"HTSeq\u2014A Python framework to work with high-throughput sequencing data","volume":"31","author":"Anders","year":"2015","journal-title":"Bioinformatics"},{"key":"ref_39","unstructured":"RStudio Team (2025, September 01). RStudio: Integrated Development Environment for, R. RStudio. Published Online. Available online: http:\/\/www.rstudio.com."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1186\/s13059-014-0550-8","article-title":"Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2","volume":"15","author":"Love","year":"2014","journal-title":"Genome Biol."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"D638","DOI":"10.1093\/nar\/gkac1000","article-title":"The STRING database in 2023: Protein\u2013protein association networks and functional enrichment analyses for any sequenced genome of interest","volume":"51","author":"Szklarczyk","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Basenko, E.Y., Pulman, J.A., Shanmugasundram, A., Harb, O.S., Crouch, K., Starns, D., Warrenfeltz, S., Aurrecoechea, C., Stoeckert, J.C.J., and Kissinger, J.C. (2018). FungiDB: An Integrated Bioinformatic Resource for Fungi and Oomycetes. J. Fungi, 4.","DOI":"10.3390\/jof4010039"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2498","DOI":"10.1101\/gr.1239303","article-title":"Cytoscape: A Software Environment for Integrated Models of Biomolecular Interaction Networks","volume":"13","author":"Shannon","year":"2003","journal-title":"Genome Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2713","DOI":"10.1093\/bioinformatics\/btw187","article-title":"DyNet: Visualization and analysis of dynamic molecular interaction networks","volume":"32","author":"Goenawan","year":"2016","journal-title":"Bioinformatics"},{"key":"ref_45","doi-asserted-by":"crossref","unstructured":"Bader, G.D., and Hogue, C.W. (2003). An automated method for finding molecular complexes in large protein interaction networks. BMC Bioinform., 4.","DOI":"10.1186\/1471-2105-4-2"},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2857","DOI":"10.1093\/bioinformatics\/btp517","article-title":"Analyzing biological network parameters with CentiScaPe","volume":"25","author":"Scardoni","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1091","DOI":"10.1093\/bioinformatics\/btp101","article-title":"ClueGO: A Cytoscape plug-in to decipher functionally grouped gene ontology and pathway annotation networks","volume":"25","author":"Bindea","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1038\/75556","article-title":"Gene Ontology: Tool for the unification of biology","volume":"25","author":"Ashburner","year":"2000","journal-title":"Nat. Genet."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"D444","DOI":"10.1093\/nar\/gkae1082","article-title":"InterPro: The protein sequence classification resource in 2025","volume":"53","author":"Blum","year":"2025","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e03457-20","DOI":"10.1128\/mBio.03457-20","article-title":"The Transcription Factor Pdr802 Regulates Titan Cell Formation and Pathogenicity of Cryptococcus neoformans","volume":"12","author":"Reuwsaat","year":"2021","journal-title":"mBio"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"1017","DOI":"10.1093\/bioinformatics\/btr064","article-title":"FIMO: Scanning for occurrences of a given motif","volume":"27","author":"Grant","year":"2011","journal-title":"Bioinformatics"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1006\/meth.2001.1262","article-title":"Analysis of Relative Gene Expression Data Using Real-Time Quantitative PCR and the 2\u2212\u0394\u0394CT Method","volume":"25","author":"Livak","year":"2001","journal-title":"Methods"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"e59","DOI":"10.1002\/cpmc.59","article-title":"Genetic Manipulation of Cryptococcus neoformans","volume":"50","author":"Jung","year":"2018","journal-title":"Curr. Protoc. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1405","DOI":"10.1128\/jb.175.5.1405-1411.1993","article-title":"Gene transfer in Cryptococcus neoformans by use of biolistic delivery of DNA","volume":"175","author":"Toffaletti","year":"1993","journal-title":"J. Bacteriol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/0022-1759(92)90209-C","article-title":"Monoclonal antibody based ELISAs for cryptococcal polysaccharide","volume":"154","author":"Casadevall","year":"1992","journal-title":"J. Immunol. Methods"},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"206","DOI":"10.1111\/j.1365-2958.2011.07686.x","article-title":"Role for Golgi reassembly and stacking protein (GRASP) in polysaccharide secretion and fungal virulence","volume":"81","author":"Kmetzsch","year":"2011","journal-title":"Mol. Microbiol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"D265","DOI":"10.1093\/nar\/gkz991","article-title":"CDD\/SPARCLE: The conserved domain database in 2020","volume":"48","author":"Lu","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"202","DOI":"10.1096\/fj.05-4581hyp","article-title":"Diverse membrane-associated proteins contain a novel SMP domain","volume":"20","author":"Lee","year":"2006","journal-title":"FASEB J."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"e01087-13","DOI":"10.1128\/mBio.01087-13","article-title":"The Cryptococcus neoformans Transcriptome at the Site of Human Meningitis","volume":"5","author":"Chen","year":"2014","journal-title":"mBio"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1128\/EC.00073-13","article-title":"The Transcriptional Response of Cryptococcus neoformans to Ingestion by Acanthamoeba castellanii and Macrophages Provides Insights into the Evolutionary Adaptation to the Mammalian Host","volume":"12","author":"Derengowski","year":"2013","journal-title":"Eukaryot. Cell"},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"4950","DOI":"10.1038\/s41467-019-12907-x","article-title":"Thermotolerance in the pathogen Cryptococcus neoformans is linked to antigen masking via mRNA decay-dependent reprogramming","volume":"10","author":"Bloom","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Trevijano-Contador, N., De Oliveira, H.C., Garc\u00eda-Rodas, R., Rossi, S.A., Llorente, I., Zaballos, \u00c1., Janbon, G., Ari\u00f1o, J., and Zaragoza, \u00d3. (2018). Cryptococcus neoformans can form titan-like cells in vitro in response to multiple signals. PLoS Pathog., 14.","DOI":"10.1371\/journal.ppat.1007007"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"e02866-22","DOI":"10.1128\/spectrum.02866-22","article-title":"Unraveling Capsule Biosynthesis and Signaling Networks in Cryptococcus neoformans","volume":"10","author":"Jang","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1128\/EC.00426-07","article-title":"Calcineurin-Responsive Zinc Finger Transcription Factor Crz1 of Botrytis cinerea Is Required for Growth, Development, and Full Virulence on Bean Plants","volume":"7","author":"Schumacher","year":"2008","journal-title":"Eukaryot. Cell"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"88","DOI":"10.1007\/s00294-005-0003-8","article-title":"Functional characterization of the Candida albicans CRZ1 gene encoding a calcineurin-regulated transcription factor","volume":"48","author":"Santos","year":"2005","journal-title":"Curr. Genet."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"1085","DOI":"10.1128\/EC.00086-08","article-title":"Calcineurin Target CrzA Regulates Conidial Germination, Hyphal Growth, and Pathogenesis of Aspergillus fumigatus","volume":"7","author":"Cramer","year":"2008","journal-title":"Eukaryot. Cell"},{"key":"ref_67","doi-asserted-by":"crossref","unstructured":"Kim, S., Hu, J., Oh, Y., Park, J., Choi, J., Lee, Y.-H., A Dean, R., and Mitchell, T.K. (2010). Combining ChIP-chip and Expression Profiling to Model the MoCRZ1 Mediated Circuit for Ca2+\/Calcineurin Signaling in the Rice Blast Fungus. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1000909"},{"key":"ref_68","unstructured":"Verli, H. (2014). Bioinform\u00e1tica: Da Biologia \u00e0 Flexibilidade Molecular, SBBq. [1st ed.]. Available online: https:\/\/www.lume.ufrgs.br\/handle\/10183\/166105."},{"key":"ref_69","doi-asserted-by":"crossref","unstructured":"Pinu, F.R., Beale, D.J., Paten, A.M., Kouremenos, K., Swarup, S., Schirra, H.J., and Wishart, D. (2019). Systems Biology and Multi-Omics Integration: Viewpoints from the Metabolomics Research Community. Metabolites, 9.","DOI":"10.3390\/metabo9040076"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"1208","DOI":"10.1007\/s00018-004-4029-8","article-title":"Characterization of the yeast tricalbins: Membrane-bound multi-C2-domain proteins that form complexes involved in membrane trafficking","volume":"61","author":"Creutz","year":"2004","journal-title":"Cell. Mol. Life Sci. CMLS"},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"100729","DOI":"10.1016\/j.jbc.2021.100729","article-title":"Calcium-dependent and -independent lipid transfer mediated by tricalbins in yeast","volume":"296","author":"Qian","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"107665","DOI":"10.1016\/j.jbc.2024.107665","article-title":"The tricalbin family of membrane contact site tethers is involved in the transcriptional responses of Saccharomyces cerevisiae to glucose","volume":"300","author":"Schlarmann","year":"2024","journal-title":"J. Biol. Chem."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"e02079-22","DOI":"10.1128\/spectrum.02079-22","article-title":"The Tricalbin-Family Endoplasmic Reticulum-Plasma Membrane Tethering Proteins Attenuate ROS-Involved Caspofungin Sensitivity in Candida albicans","volume":"10","author":"Yang","year":"2022","journal-title":"Microbiol. Spectr."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Yu, H., Kim, P.M., Sprecher, E., Trifonov, V., and Gerstein, M. (2007). The Importance of Bottlenecks in Protein Networks: Correlation with Gene Essentiality and Expression Dynamics. PLoS Comput. Biol., 3.","DOI":"10.1371\/journal.pcbi.0030059"},{"key":"ref_75","doi-asserted-by":"crossref","unstructured":"O\u2019Meara, M.J., Rapala, J.R., Nichols, C.B., Alexandre, A.C., Billmyre, R.B., Steenwyk, J.L., Alspaugh, J.A., and O\u2019meara, T.R. (2024). CryptoCEN: A Co-Expression Network for Cryptococcus neoformans reveals novel proteins involved in DNA damage repair. PLoS Genet., 20.","DOI":"10.1371\/journal.pgen.1011158"},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"133","DOI":"10.1016\/S0065-2164(09)01204-0","article-title":"Chapter 4 The Capsule of the Fungal Pathogen Cryptococcus neoformans","volume":"68","author":"Zaragoza","year":"2009","journal-title":"Adv. Appl. Microbiol."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"48","DOI":"10.1128\/EC.00318-06","article-title":"Vesicular Polysaccharide Export in Cryptococcus neoformans Is a Eukaryotic Solution to the Problem of Fungal Trans-Cell Wall Transport","volume":"6","author":"Rodrigues","year":"2007","journal-title":"Eukaryot. Cell"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1128\/EC.00370-07","article-title":"Extracellular Vesicles Produced by Cryptococcus neoformans Contain Protein Components Associated with Virulence","volume":"7","author":"Rodrigues","year":"2008","journal-title":"Eukaryot. Cell"}],"container-title":["Microorganisms"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/1\/122\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T09:38:53Z","timestamp":1769161133000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-2607\/14\/1\/122"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,7]]},"references-count":78,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2026,1]]}},"alternative-id":["microorganisms14010122"],"URL":"https:\/\/doi.org\/10.3390\/microorganisms14010122","relation":{},"ISSN":["2076-2607"],"issn-type":[{"value":"2076-2607","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,1,7]]}}}