Biology subjects

Modha, S.

Publications and source records attributed to Modha, S..

3 recordsLinked to original sources

bioRxiv2024

Diversity and evolution of the human anellome

Anelloviruses are a group of small, circular, single-stranded DNA viruses that are found ubiquitously across mammalian hosts. Here, we explored a large number of publicly available human microbiome datasets and retrieved a total of 829 anellovirus genomes, substantially expanding the known diversity of these viruses. The majority of new genomes fall within the three major human anellovirus genera: Alphatorquevirus, Betatorquevirus and Gammatorquevirus, while we also present one new genome of the under-sampled Hetorquevirus genus. The phylogeny reconstructed from the conserved ORF1 gene reveals three additional, previously undescribed, human anellovirus clades. We performed recombination analysis and show evidence of extensive recombination across all human anelloviruses. Interestingly, more than 95% of the detected events are between members of the same clade and only 15 inter-clade recombination events were detected. The breakpoints of recombination cluster in hotspots at the ends and outside of the ORF1 gene, while a recombination coldspot was detected within the gene. Our analysis suggests that anellovirus evolution is governed by homologous recombination, however events between distant viruses or ones producing chimaeric ORF1s likely lead to non-viable recombinants. The large number of genomes further allowed us to examine how essential genomic features vary across anelloviruses. These include functional domains in the ORF1 protein and the nucleotide motif of the replication loop region, required for the viruses rolling-circle replication. A subset of the genomes assembled in both this and previous studies are completely lacking these essential elements, opening up the possibility that anellovirus intracellular populations contain defective virus genomes (DVGs). Overall, our study highlights key features of anellovirus genomics and evolution, a largely understudied group of viruses whose potential in virus-based therapeutics is recently being explored.

evolutionary biology↗

bioRxiv2021

Quantifying and cataloguing unknown sequences within human microbiomes

Advances in genome sequencing technologies and lower costs have enabled the exploration of a multitude of known and novel environments and microbiomes. This has led to an exponential growth in the raw sequence data that is deposited in online repositories. Metagenomic and metatranscriptomic data sets are typically analysed with regards to a specific biological question. However, it is widely acknowledged that these data sets are comprised of a proportion of sequences that bear no similarity to any currently known biological sequence, and this so-called dark matter is often excluded from downstream analyses. In this study, a systematic framework was developed to assemble, identify, and measure the proportion of unknown sequences present in distinct human microbiomes. This framework was applied to forty distinct studies, comprising 963 samples, and covering ten different human microbiomes including fecal, oral, lung, skin and circulatory system microbiomes. The framework was used to determine the proportion of taxonomically unknown sequences present within samples, and to compare such sequences both within and across assembled metagenomes. We found that whilst the human microbiome is one of the most extensively studied, on average 2% of assembled sequences have not yet been taxonomically defined. However, this proportion varied extensively among different microbiomes and was as high as 25% for skin and oral microbiomes that have more interactions with the environment. The publicly available data sets used have not previously been systematically mined to quantify and compare such dark matter. Typically, these unknown sequences are found in several microbiomes and potentially belong to unidentified novel microbes that we interact with on a daily basis. A cross-study comparison led to the identification of similar unknown sequences in different samples and/or microbiomes. A rate of taxonomic characterisation of 1.64% of unknown sequences being characterised per month was calculated from these taxonomically unknown sequences discovered in this study. Additionally, the approach led to the discovery of several potentially novel viral genomes that bear no similarity to sequences in the public databases. Both our computational framework and the novel unknown sequences produced are publicly available for future cross-referencing.

bioinformatics↗

bioRxiv2018

Whole-genome sequencing of parvoviruses from wild and domestic animals in Brazil provides new insights into parvovirus distribution and diversity

AbstractParvoviruses (family Parvoviridae) are small, single-stranded DNA viruses. Many parvoviral pathogens of medical, veterinary and ecological importance have been identified. In this study, we used high-throughput sequencing (HTS) to investigate the diversity of parvoviruses infecting wild and domestic animals in Brazil. We identified 21 parvovirus sequences (including twelve nearly complete genomes and nine partial genomes) in samples derived from rodents, bats, opossums, birds and cattle in Pernambuco, Sao Paulo, Parana and Rio Grande do Sul states. These sequences were investigated using phylogenetic and distance-based approaches, and were thereby classified into eight parvovirus species (six of which have not been described previously), representing six distinct genera in the subfamily Parvovirinae. Our findings extend the known biogeographic range of previously characterized parvovirus species, and the known host range of three parvovirus genera (Dependovirus, Aveparvovirus, and Tetraparvovirus). Moreover, our investigation provides a window into the ecological dynamics of parvovirus infections in vertebrates, revealing that many parvovirus genera contain well-defined sub-lineages that circulate widely throughout the world within particular taxonomic groups of hosts.

microbiology↗