Biology subjects

Jackson, D. K.

Publications and source records attributed to Jackson, D. K..

3 recordsLinked to original sources

bioRxiv2025

Benchmarking of Human ReadRemoval Strategies for Viral andMicrobial Metagenomics

Human reads are a key contaminant in microbial metagenomics and enrichment-based studies, requiring removal for computational efficiency, biological analysis, and privacy protection. Various in silico methods exist, but their effectiveness depends on the parameters and reference genomes used. Here, we assess different methods, including the impact of the updated T2T-CHM13 human genome versus GRCh38. Using a synthetic dataset of viral and human reads, we evaluated performance metrics for multiple approaches. We found that the usage of high-sensitivity configuration of Bowtie2 with the T2T-CHM13 reference assembly significantly improves human read removal with minimal loss of specificity, albeit at higher computational cost compared to other methods investigated. Applying this approach to a publicly available microbiome dataset, we effectively removed sex-determining SNPs with little impact on microbial assembly. Our results suggest that our high-sensitivity Bowtie2 approach with the T2T-CHM13 is the best method tested to minimise identifiability risks from residual human reads.

genomics↗

bioRxiv2023

Anaerobic fungi in the tortoise alimentary tract illuminate early stages of host-fungal symbiosis and Neocallimastigomycota evolution

The anaerobic gut fungi (AGF, Neocallimastigomycota) reside in the alimentary tract of herbivores. While their presence in mammals is well documented, evidence for their occurrence in non-mammalian hosts is currently sparse. Here we report on AGF communities in tortoises (family Testudinidae). Culture-independent surveys of tortoise fecal samples identified a unique AGF community, with three novel deep-branching genera representing >90% of sequences in most samples. Representatives of all genera were successfully isolated under strict anaerobic conditions at 30{degrees}C or 39{degrees}C. Transcriptomics-enabled phylogenomic and molecular dating analysis indicated an ancient, deep-branching position in the AGF tree for these genera, with an evolutionary divergence time estimate of 104-112 million years ago (Mya). Such estimates push the establishment of animal- Neocallimastigomycota symbiosis from the early Paleogene (67 Mya) to the early Cretaceous (112 Mya). Further, compared to their mammalian counterparts, tortoise-associated isolates exhibited a more limited capacity for plant polysaccharides metabolism and lacked genes encoding several carbohydrate active enzyme (CAZyme) families mediating their degradation. Finally, we demonstrate that the observed curtailed degradation capacities and reduced CAZyme repretoire in tortoise-associated AGF is driven by the paucity of horizontal gene transfer (HGT) in tortoise-associated AGF genomes, compared to the massive HGT occurrence in mammalian AGF taxa. The reduced CAZyome and overall secretory machinery observed is also reflected in an altered cellulosomal production capacity in tortoise-associated AGF. Our findings provide novel insights into the scope of phylogenetic diversity, ecological distribution, evolutionary history, evolution of fungal-host nutritional symbiosis, and dynamics of genes and traits acquisition in Neocallimastigomycota. SignificanceAnaerobic gut fungi (AGF) are encountered in the rumen and hindgut of mammalian herbivores. However, their occurrence outside their canonical mammalian hosts is currently unclear. We report the identification, isolation, and characterization of novel, deep-branching AGF genera from tortoises. Such discovery expands the phylogenetic diversity and host range of the AGF and revises estimates of the phylums evolutionary time to the early Cretaceous (112 Mya). We also demonstrate that tortoise-sourced AGF lack multiple metabolic features compared to their mammalian counterparts, and identify the relative paucity of HGT events in tortoise-associated genera as a major factor underpinning such differences. Our results alter our understanding of the scope of phylogenetic diversity, ecological distribution, and evolutionary history of the AGF.

microbiology↗

bioRxiv2020

Patterns of within-host genetic diversity in SARS-CoV-2

Monitoring the spread of SARS-CoV-2 and reconstructing transmission chains has become a major public health focus for many governments around the world. The modest mutation rate and rapid transmission of SARS-CoV-2 prevents the reconstruction of transmission chains from consensus genome sequences, but within-host genetic diversity could theoretically help identify close contacts. Here we describe the patterns of within-host diversity in 1,181 SARS-CoV-2 samples sequenced to high depth in duplicate. 95% of samples show within-host mutations at detectable allele frequencies. Analyses of the mutational spectra revealed strong strand asymmetries suggestive of damage or RNA editing of the plus strand, rather than replication errors, dominating the accumulation of mutations during the SARS-CoV-2 pandemic. Within and between host diversity show strong purifying selection, particularly against nonsense mutations. Recurrent within-host mutations, many of which coincide with known phylogenetic homoplasies, display a spectrum and patterns of purifying selection more suggestive of mutational hotspots than recombination or convergent evolution. While allele frequencies suggest that most samples result from infection by a single lineage, we identify multiple putative examples of co-infection. Integrating these results into an epidemiological inference framework, we find that while sharing of within-host variants between samples could help the reconstruction of transmission chains, mutational hotspots and rare cases of superinfection can confound these analyses.

genomics↗