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      Isolate-specific rat brain transcriptional responses to rat lungworm ( Angiostrongylus cantonensis)

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          Abstract

          The rat lungworm ( Angiostrongylus cantonensis) is an invasive parasite of rats that in accidental hosts, such as dogs and humans, causes eosinophilic meningitis. In Australia, only two distinct rat lungworm cox1 haplotypes have been detected in clinically affected dogs, with haplotype Ac13 implicated in most cases. Using locally sourced isolates, we enquired whether the brain migrating larvae elicit different host response in its natural host. We examined brain transcriptome, faecal shedding rates, and adult worm of A. cantonensis isolates representing two distinct cox1 haplotypes, SYD.1 and Ac13 (represented by isolate SYD.2), in experimentally infected Wistar rats. For SYD.1-infected rats, only one differentially expressed gene (DEG) was upregulated in the compared to controls. In contrast, the transcriptome of SYD.2-infected rats included 100 DEGs, with enrichment of functional terms related to immune response, neuroactivity, and signalling. Faecal shedding did not differ between SYD.1- and SYD.2-infected rats, but adult worm burdens were higher in the SYD.1 group. The increased immune response in SYD.2-infected rats provides evidence that there is strain specific virulence that is pronounced in its natural host. This study provides initial parasite-specific evidence explaining why clinically affected dogs are more frequently presented with A. cantonensis haplotype Ac13.

          Abstract

          Brain-invading Angiostrongylus cantonensis infects various animals, including humans, with brain reactions varying based on the parasite’s specific identity. Two different Australian isolates of rat lungworm ( Angiostrongylus cantonensis) trigger different responses from the definitive (rat) host during experimental infection.

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          Most cited references63

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
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            featureCounts: an efficient general purpose program for assigning sequence reads to genomic features.

            Next-generation sequencing technologies generate millions of short sequence reads, which are usually aligned to a reference genome. In many applications, the key information required for downstream analysis is the number of reads mapping to each genomic feature, for example to each exon or each gene. The process of counting reads is called read summarization. Read summarization is required for a great variety of genomic analyses but has so far received relatively little attention in the literature. We present featureCounts, a read summarization program suitable for counting reads generated from either RNA or genomic DNA sequencing experiments. featureCounts implements highly efficient chromosome hashing and feature blocking techniques. It is considerably faster than existing methods (by an order of magnitude for gene-level summarization) and requires far less computer memory. It works with either single or paired-end reads and provides a wide range of options appropriate for different sequencing applications. featureCounts is available under GNU General Public License as part of the Subread (http://subread.sourceforge.net) or Rsubread (http://www.bioconductor.org) software packages.
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              HISAT: a fast spliced aligner with low memory requirements.

              HISAT (hierarchical indexing for spliced alignment of transcripts) is a highly efficient system for aligning reads from RNA sequencing experiments. HISAT uses an indexing scheme based on the Burrows-Wheeler transform and the Ferragina-Manzini (FM) index, employing two types of indexes for alignment: a whole-genome FM index to anchor each alignment and numerous local FM indexes for very rapid extensions of these alignments. HISAT's hierarchical index for the human genome contains 48,000 local FM indexes, each representing a genomic region of ∼64,000 bp. Tests on real and simulated data sets showed that HISAT is the fastest system currently available, with equal or better accuracy than any other method. Despite its large number of indexes, HISAT requires only 4.3 gigabytes of memory. HISAT supports genomes of any size, including those larger than 4 billion bases.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: Data curationRole: Formal analysisRole: InvestigationRole: MethodologyRole: Project administrationRole: VisualizationRole: Writing - original draft
                Role: Project administrationRole: ResourcesRole: Supervision
                Role: ConceptualizationRole: Funding acquisitionRole: MethodologyRole: Project administrationRole: ResourcesRole: SupervisionRole: Writing - review & editing
                Journal
                Pathog Dis
                Pathog Dis
                femspd
                Pathogens and Disease
                Oxford University Press
                2049-632X
                2025
                19 February 2025
                19 February 2025
                : 83
                : ftaf003
                Affiliations
                Sydney School of Veterinary Science, Faculty of Science, The University of Sydney , NSW 2006, Australia
                NSW Health Pathology, Centre for Infectious Diseases and Microbiology Lab Services, Level 3 ICPMR, Westmead Hospital , Westmead, NSW 2145, Australia
                School of Biomedical Sciences, Faculty of Medicine and Health, The University of Sydney , NSW 2006, Australia
                Sydney School of Veterinary Science, Faculty of Science, The University of Sydney , NSW 2006, Australia
                Sydney Infectious Diseases Institute, The University of Sydney , NSW 2006, Australia
                Author notes
                Corresponding author. Rm 202, McMaster Building (B14), Sydney School of Veterinary Science, The University of Sydney, NSW 2006, Australia. E-mail: jan.slapeta@ 123456sydney.edu.au
                Author information
                https://orcid.org/0000-0003-1459-9117
                Article
                ftaf003
                10.1093/femspd/ftaf003
                11895509
                39971741
                60da7cf1-a06f-4405-a307-57c916da387d
                © The Author(s) 2025. Published by Oxford University Press on behalf of FEMS.

                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
                : 24 November 2024
                : 12 February 2025
                : 17 February 2025
                : 11 March 2025
                Page count
                Pages: 14
                Funding
                Funded by: Sydney School of Veterinary Sciences;
                Funded by: University of Sydney, DOI 10.13039/501100001774;
                Categories
                Research Article
                AcademicSubjects/SCI01150

                rna-seq,transcriptomics,immunity,haplotype,angiostrongyliasis,australia

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