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      Acquisition of cross-azole tolerance and aneuploidy in Candida albicans strains evolved to posaconazole

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          Abstract

          A number of in vitro studies have examined the acquisition of drug resistance to the triazole fluconazole, a first-line treatment for many Candida infections. Much less is known about posaconazole, a newer triazole. We conducted the first in vitro experimental evolution of replicates from 8 diverse strains of Candida albicans in a high level of the fungistatic drug posaconazole. Approximately half of the 132 evolved replicates survived 50 generations of evolution, biased toward some of the strain backgrounds. We found that although increases in drug resistance were rare, increases in drug tolerance (the slow growth of a subpopulation of cells in a level of drug above the resistance level) were common across strains. We also found that adaptation to posaconazole resulted in widespread cross-tolerance to other azole drugs. Widespread aneuploidy was observed in evolved replicates from some strain backgrounds. Trisomy of at least one of chromosomes 3, 6, and R was identified in 11 of 12 whole-genome sequenced evolved SC5314 replicates. These findings document rampant evolved cross-tolerance among triazoles and highlight that increases in drug tolerance can evolve independently of drug resistance in a diversity of C. albicans strain backgrounds.

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          Trimmomatic: a flexible trimmer for Illumina sequence data

          Motivation: Although many next-generation sequencing (NGS) read preprocessing tools already existed, we could not find any tool or combination of tools that met our requirements in terms of flexibility, correct handling of paired-end data and high performance. We have developed Trimmomatic as a more flexible and efficient preprocessing tool, which could correctly handle paired-end data. Results: The value of NGS read preprocessing is demonstrated for both reference-based and reference-free tasks. Trimmomatic is shown to produce output that is at least competitive with, and in many cases superior to, that produced by other tools, in all scenarios tested. Availability and implementation: Trimmomatic is licensed under GPL V3. It is cross-platform (Java 1.5+ required) and available at http://www.usadellab.org/cms/index.php?page=trimmomatic Contact: usadel@bio1.rwth-aachen.de Supplementary information: Supplementary data are available at Bioinformatics online.
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            The Sequence Alignment/Map format and SAMtools

            Summary: The Sequence Alignment/Map (SAM) format is a generic alignment format for storing read alignments against reference sequences, supporting short and long reads (up to 128 Mbp) produced by different sequencing platforms. It is flexible in style, compact in size, efficient in random access and is the format in which alignments from the 1000 Genomes Project are released. SAMtools implements various utilities for post-processing alignments in the SAM format, such as indexing, variant caller and alignment viewer, and thus provides universal tools for processing read alignments. Availability: http://samtools.sourceforge.net Contact: rd@sanger.ac.uk
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              NIH Image to ImageJ: 25 years of image analysis

              For the past twenty five years the NIH family of imaging software, NIH Image and ImageJ have been pioneers as open tools for scientific image analysis. We discuss the origins, challenges and solutions of these two programs, and how their history can serve to advise and inform other software projects.
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                Author and article information

                Contributors
                Role: Editor
                Journal
                G3 (Bethesda)
                Genetics
                g3journal
                G3: Genes|Genomes|Genetics
                Oxford University Press
                2160-1836
                September 2022
                26 July 2022
                26 July 2022
                : 12
                : 9
                : jkac156
                Affiliations
                Department of Microbiology, The University of Manitoba , Winnipeg, MB R3T 2N2, Canada
                Department of Microbiology, The University of Manitoba , Winnipeg, MB R3T 2N2, Canada
                Department of Microbiology, The University of Manitoba , Winnipeg, MB R3T 2N2, Canada
                Department of Microbiology, The University of Manitoba , Winnipeg, MB R3T 2N2, Canada
                Department of Microbiology, The University of Manitoba , Winnipeg, MB R3T 2N2, Canada
                Department of Microbiology, The University of Manitoba , Winnipeg, MB R3T 2N2, Canada
                Department of Microbiology, The University of Manitoba , Winnipeg, MB R3T 2N2, Canada
                Department of Statistics, The University of Manitoba , Winnipeg, MB R3T 2N2, Canada
                Author notes
                Corresponding author: Department of Microbiology, The University of Manitoba, 45 Chancellor Circle, 213 Buller Building, Winnipeg, MB R3T 2N2, Canada. Email: aleeza.gerstein@ 123456umanitoba.ca
                [†]

                Madison Chape and Quinn Wonitowy contributed equally to this work.

                Author information
                https://orcid.org/0000-0002-3967-3216
                https://orcid.org/0000-0002-2661-2916
                https://orcid.org/0000-0002-7495-3176
                https://orcid.org/0000-0002-0923-3893
                https://orcid.org/0000-0002-8203-7362
                https://orcid.org/0000-0002-7474-5510
                https://orcid.org/0000-0002-0781-9356
                Article
                jkac156
                10.1093/g3journal/jkac156
                9434289
                35881695
                ca03cb62-b018-4518-890b-9e0adb5c77cd
                © The Author(s) 2022. Published by Oxford University Press on behalf of Genetics Society of America.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution License ( https://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 13 June 2022
                : 06 January 2022
                : 27 July 2022
                Page count
                Pages: 12
                Funding
                Funded by: NSERC Discovery Grant;
                Funded by: University of Manitoba and a University of Manitoba University Research Grants Program;
                Funded by: University of Manitoba, Faculty of Science;
                Funded by: NSERC Undergraduate Student Research Awards;
                Funded by: EvoFunPath (NSERC CREATE);
                Categories
                Investigation
                AcademicSubjects/SCI01180
                AcademicSubjects/SCI01140
                AcademicSubjects/SCI00010
                AcademicSubjects/SCI00960

                Genetics
                drug resistance,drug tolerance,aneuploidy,experimental evolution
                Genetics
                drug resistance, drug tolerance, aneuploidy, experimental evolution

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