Biology subjects

Zdobnov, E. M.

Publications and source records attributed to Zdobnov, E. M..

15 recordsLinked to original sources

bioRxiv2025

LEMMIv2: Benchmarking Framework for Metagenomic and 16S Amplicon Profilers with a Catalogue of Evaluated Tools.

Sequencing has transformed microbial studies, enabling metagenomic analysis of microbial communities without the need for culturing or prior knowledge of sample composition. The essential analysis of the primary sequencing reads, however, is complex and led to the development of diverse computational strategies. The plethora of available methods and their numerous parameters poses a practical challenge for practitioners and creates a visibility barrier for developers of novel approaches. In addition to technical limitations related to user computing environment, algorithmic solutions, and their scalability, there are critical considerations regarding the reference database, i.e. the knowledge against which the data is interpreted, as well as the target of the analysis, expected sample composition, and peculiarities of read data from different sequencing platforms. To facilitate informed decision-making, we introduced the LEMMI platform for continuous benchmarking of software tools for metagenomic analyses, where developers can receive impartial benchmarks for method publication and users benefit from a standardized and benchmarked catalogue of tools. Here we present developments of LEMMI version 2, including assessments of different target scenarios, long- and short-read sequencing data, alternative taxonomies, and a standalone pipeline (https://lemmi.ezlab.org). In addition to LEMMI, which focuses on shotgun metagenomic profiling, we extended this approach to bacteria profiling with 16S amplicon sequencing (https://lemmi16S.ezlab.org).

genomics↗

bioRxiv2025

Human gut microbiota subspecies carry implicit information for in-depth microbiome research

Microbial strains from same species can have distinct functional characteristics owing to their different gene content. As the highest resolution, strains are mainly host-specific, thus obscuring unbiased associations, and hindering deductive research. Here, we comprehensively define the human gut microbiota at consistently-annotated subspecies resolution in an unbiased, cohort-independent manner, and demonstrate that we can generalize across distinct populations worldwide while maintaining specificity and improving interstudy reproducibility. We developed panhashome, a sketching-based method for rapid subspecies quantification and identification of genes that drive the intraspecies variations, and showed that subspecies carry implicit information undetectable at species level. By meta-analysis of colorectal cancer (CRC) datasets, we identified disease-associated subspecies whose sibling subspecies or species are not. Subspecies-based machine-learning CRC diagnostic algorithm outperformed species-level methods by leveraging the unique subspecies-level information. This subspecies catalogue allows identification of genes that drive the functional differences between subspecies as fundamental step in mechanistically understanding microbiome-phenotype interactions.

bioinformatics↗

bioRxiv2021

Mitochondrial mutational spectrum is associated with mammalian longevity: a novel signature of oxidative damage.

The mutational spectrum of the mitochondrial DNA (mtDNA) does not resemble any of the known mutational signatures of the nuclear genome and variation in mtDNA mutational spectra between different organisms is still incomprehensible. Since mitochondria is tightly involved in aerobic energy production, it is expected that mtDNA mutational spectra is affected by the oxidative damage. Assuming that oxidative damage increases with age, we analyze mtDNA mutagenesis of different species. Analysing (i) dozens thousands of somatic mtDNA mutations in samples of different age (ii) 70053 polymorphic synonymous mtDNA substitutions, reconstructed in 424 mammalian species with different generation length and (iii) synonymous nucleotide content of 650 complete mitochondrial genomes of mammalian species we observed that the frequency of AH>GH substitutions (H - heavy chain notation) is twice higher in species with high versus low generation length making their mtDNA more AH poor and GH rich. Considering that AH>GH substitutions are also sensitive to the time spent single stranded (TSSS) during asynchroniuos mtDNA replication we demonstrated that AH>GH substitution rate is a function of both species-specific generation length and position specific TSSS. We propose that AH>GH is a mitochondria-specific signature of oxidative damage associated with both aging and TSSS.

bioinformatics↗

bioRxiv2021

Tsetse RNA Virome: Novel Iflavirus Genomes in Glossina morsitans and Other Tsetse Species

Tsetse flies (Glossina spp.) are vectors of Human and Animal African trypanosomiasis. The tsetse microbiome has been extensively studied in the context of bacterial endosymbiont-host interactions, however, remarkably little is known about the tsetse virome with only one well-characterized DNA virus, the salivary gland hypertrophy virus (SGHV). Here we report the genomes of four iflaviruses identified in tsetse flies and their distribution in public RNA-seq libraries, mainly from laboratory colonies. Strikingly, the iflavirus identified in G. morsitans, provisionally named Glossina iflavirus 1 (GliflaV1), is present in all 136 RNA-seq libraries of G. morsitans maintained at different institutions, and displays a broad tissue tropism and high abundance, reaching up to 15% of library content. Its ubiquitous distribution and presence in the reproductive tissues, intrauterine larvae, and teneral flies suggest it is part of the initial core microbiota maternally transmitted to the progeny. None of the G. morsitans samples harbor iflaviruses identified in the other three, more closely related, tsetse species which, conversely, do not harbor the iflavirus from G. morsitans. Though apparently asymptomatic, these infections may influence tsetse host fitness, developmental or biological processes which might be relevant in the context of tsetse population control strategies, mass rearing, and paratransgenesis, and open up new opportunities to study the quadripartite system of interactions among the invertebrate host, the parasitic protozoan, and both viral and bacterial symbionts.

zoology↗

bioRxiv2021

Bacterial, phytoplankton, and viral dynamics of meromictic Lake Cadagno offer insights into the Proterozoic ocean microbial loop

Lake Cadagno, a permanently stratified high-alpine lake with a persistent microbial bloom in its anoxic chemocline, has long been considered a model for the low-oxygen, high-sulfide Proterozoic ocean where early microbial life gave rise to Earths oxygenated atmosphere. Although the lake has been studied for over 25 years, the absence of concerted study of the bacteria, phytoplankton, and viruses, together with primary and secondary production, has hindered a comprehensive understanding of its microbial food web. Here, the identities, abundances, and productivity of microbes were evaluated in the context of Lake Cadagno biogeochemistry. Photo-synthetic pigments and chloroplast 16S rRNA gene phylogenies suggested high abundances of eukaryotic phytoplankton, primarily Chlorophyta, through the water column. Of these, a close relative of Ankyra judayi, a high-alpine adapted chlorophyte, peaked with oxygen in the mixolimnion, while Closteriopsis-related chlorophytes peaked in the chemocline and monimolimnion. Anoxygenic phototrophic sulfur bacteria, Chromatium, dominated the chemocline along with Lentimicrobium, a newly observed genus of known fermenters. Secondary production peaked in the chemocline, suggesting anoxygenic primary producers depended on heterotrophic nutrient remineralization. Virus-to-microbe ratios spanned an order of magnitude, peaking with high phytoplankton abundances and at a minimum at the peak of Chromatium, dynamic trends that suggest viruses may play a role in the modulation of oxygenic and anoxygenic photo- and chemosynthesis in Lake Cadagno. Through the combined analysis of bacterial, eukaryotic, viral, and biogeochemical dynamics of Lake Cadagno, this study provides a new perspective on the biological and geochemical connections that comprised the food webs of the Proterozoic ocean. IMPORTANCEAs a window to the past, the study offers insights into the role of microbial guilds of Proterozoic ocean chemoclines in the production and recycling of organic matter of sulfur- and ammonia-containing ancient oceans. The new observations described here suggest that eukaryotic algae were persistent in the low oxygen upper-chemocline in association with purple and green sulfur bacteria in the lower half of the chemocline. Further, this study provides the first insights into Lake Cadagno viral ecology. High viral abundances suggested viruses may be essential components of the chemocline where their activity may result in the release and recycling of organic matter. The framework developed in this study through the integration of diverse geochemical and biological data types lays the foundation for future studies to quantitatively resolve the processes performed by discrete populations comprising the microbial loop in this early anoxic ocean analogue.

microbiology↗

bioRxiv2021

Microbial loop of Proterozoic ocean analogue

Meromictic Lake Cadagno, an ancient ocean analogue, is known for its permanent stratification and persistent anoxygenic microbial bloom within the chemocline. Although the anaerobic microbial ecology of the lake has been extensively studied for at least 25 years, a comprehensive picture of the microbial food web linking the bacterial layer to phytoplankton and viruses, with explicit measures of primary and secondary production, is still missing. This study sought to better understand the abundances and productivity of microbes in the context of nutrient biogeochemical cycling across the stratified zones of Lake Cadagno. Photosynthetic pigments and chloroplast 16S rRNA gene phylogenies suggested the presence of eukaryotic phytoplankton through the water column. Evidence supported high abundances of Ankyra judayi, a high-alpine adapted chlorophyte, in the oxic mixolimnion where oxygenic-primary production peaked. Through the no- and low-oxygen chemocline and monimolimnion, chlorophytes related to Closteriopsis acicularis, a known genus of meromictic lakes, and Parachlorella kessleri were observed. Chromatium, anoxygenic phototrophic sulfur bacteria, dominated the chemocline along with Lentimicrobium, a genus of known fermenters whose abundance was newly reported in Lake Cadagno. Secondary production peaked in the chemocline suggesting primary producers depend on hetrotrophs for nutrient remineralization. As previously observed, sulfur reducing bacteria (SRBs), especially Desulfocapsa and Desulfobulbus, were present in the chemocline and anoxic monimolimnion. Virus-to-microbe ratios (VMR) peaked in the zone of phytoplankton, yet were at a minimum at the peak of Chromatium. These dynamic trends suggest viruses may play a role in the modulation of oxygenic and anoxygenic photo- and chemosynthesis in Lake Cadagno and other permanently stratified systems. ImportanceAs a window to the past, the study offers insights into the role of microbial guilds of Proterozoic ocean chemoclines in the production and recycling of organic matter of sulfur- and ammonia-containing ancient oceans. The new observations described here suggest that eukaryotic algae were persistent in the low oxygen upper-chemocline in association with purple and green sulfur bacteria in the lower half of the chemocline. Further, this study provides the first insights into Lake Cadagno viral ecology. High viral abundances suggested viruses may be essential components of the chemocline where their activity may result in the release and recycling of organic matter. The framework developed in this study through the integration of diverse geochemical and biological data types lays the foundation for future studies to quantitatively resolve the processes performed by discrete populations comprising the microbial loop in this early anoxic ocean analogue.

microbiology↗

bioRxiv2020

Microbial contaminants cataloged as novel human sequences in recent human pan-genomes

Human pan-genome studies offer the opportunity to identify human non-reference sequences (NRSs) which are, by definition, not represented in the reference human genome (GRCh38). NRSs serve as useful catalogues of genetic variation for population and disease studies and while the majority consists of repetitive elements, a substantial fraction is made of non-repetitive, non-reference (NRNR) sequences. The presence of non-human sequences in these catalogues can inflate the number of "novel" human sequences, overestimate the genetic differentiation among populations, and jeopardize subsequent analyses that rely on these resources. We uncovered almost 2,000 contaminant sequences of microbial origin in NRNR sequences from recent human pan-genome studies. The contaminant contigs (3,501,302 bp) harbour genes totalling 4,720 predicted proteins (>40 aa). The major sources of contamination are related to Rhyzobiales, Burkholderiales, Pseudomonadales and Lactobacillales, which may have been associated with the original samples or introduced later during sequencing experiments. We additionally observed that the majority of human novel protein-coding genes described in one of the studies entirely overlap repetitive regions and are likely to be false positive predictions. We report here the list of contaminant sequences in three recent human pan-genome catalogues and discuss strategies to increase decontamination efficacy for current and future pan-genome studies.

genomics↗

bioRxiv2019

ATLAS: a Snakemake workflow for assembly, annotation, and genomic binning of metagenome sequence data

BackgroundMetagenomics and metatranscriptomics studies provide valuable insight into the composition and function of microbial populations from diverse environments, however the data processing pipelines that rely on mapping reads to gene catalogs or genome databases for cultured strains yield results that underrepresent the genes and functional potential of uncultured microbes. Recent improvements in sequence assembly methods have eased the reliance on genome databases, thereby allowing the recovery of genomes from uncultured microbes. However, configuring these tools, linking them with advanced binning and annotation tools, and maintaining provenance of the processing continues to be challenging for researchers.\n\nResultsHere we present ATLAS, a software package for customizable data processing from raw sequence reads to functional and taxonomic annotations using state-of-the-art tools to assemble, annotate, quantify, and bin metagenome and metatranscriptome data. Genome-centric resolution and abundance estimates are provided for each sample in a dataset. ATLAS is written in Python and the workflow implemented in Snakemake; it operates in a Linux environment, and is compatible with Python 3.5+ and Anaconda 3+ versions. The source code for ATLAS is freely available, distributed under a BSD-3 license.\n\nConclusionATLAS provides a user-friendly, modular and customizable Snakemake workflow for metagenome and metatranscriptome data processing; it is easily installable with conda and maintained as open-source on GitHub at https://github.com/metagenome-atlas/atlas.

bioinformatics↗

bioRxiv2019

Novel Rhabdovirus and an almost complete drain fly transcriptome recovered from two independent contaminations of clinical samples.

Metagenomic approaches enable an open exploration of microbial communities without requiring a priori knowledge of a samples composition by shotgun sequencing the total RNA or DNA of the sample. Such an approach is valuable for exploratory diagnostics of novel pathogens in clinical practice. Yet, one may also identify surprising off-target findings. Here we report a mostly complete transcriptome from a drain fly (likely Psychoda alternata) as well as a novel Rhabdovirus-like virus recovered from two independent contaminations of RNA sequencing libraries from clinical samples of cerebral spinal fluid (CSF) and serum, out of a total of 724 libraries sequenced at the same laboratory during a 2-year time span. This drain fly genome shows a considerable divergence from previously sequenced insects, which may obscure common clinical metagenomic analyses not expecting such contaminations. The classification of these contaminant sequences allowed us to identify infected drain flies as the likely origin of the novel Rhabdovirus-like sequence, which could have been erroneously linked to human pathology, had they been ignored.

bioinformatics↗

bioRxiv2019

Functional genomics of the stable fly, Stomoxys calcitrans, reveals mechanisms underlying reproduction, host interactions, and novel targets for pest control

BackgroundThe stable fly, Stomoxys calcitrans, is a major blood-feeding pest of livestock that has near worldwide distribution, causing an annual cost of over $2 billion for control and product loss in the United States alone. Control of these flies has been limited to increased sanitary management practices and insecticide application for suppressing larval stages. Few genetic and molecular resources are available to help in developing novel methods for controlling stable flies.\n\nResultsThis study examines stable fly biology by utilizing a combination of high-quality genome sequencing, microbiome analyses, and RNA-seq analyses targeting multiple developmental stages and tissues. In conjunction, manual curation of over 1600 genes was used to examine gene content related to stable fly reproduction, interactions with their host, host-microbe dynamics, and putative routes for control. Most notable was establishment of reproduction-associated genes and identification of expanded vision, chemosensation, immune repertoire, and metabolic detoxification pathway gene families.\n\nConclusionsThe combined sequencing, assembly, and curation of the male stable fly genome followed by RNA-seq and downstream analyses provide insights necessary to understand the biology of this important pest. These resources and knowledge will provide the groundwork for expanding the tools available to control stable fly infestations. The close relationship of Stomoxys to other blood-feeding (Glossina) and non-blood-feeding flies (medflies, Drosophila, house flies) will allow for understanding the evolution of blood feeding among Cyclorrhapha flies.

genomics↗

bioRxiv2019

Phigaro: high throughput prophage sequence annotation

SummaryPhigaro is a standalone command-line application that is able to detect prophage regions taking raw genome and metagenome assemblies as an input. It also produces dynamic annotated \"prophage genome maps\" and marks possible transposon insertion spots inside prophages. It provides putative taxonomic annotations that can distinguish tailed from non-tailed phages. It is applicable for mining prophage regions from large metagenomic datasets.\n\nAvailabilitySource code for Phigaro is freely available for download at https://github.com/bobeobibo/phigaro along with test data. The code is written in Python.

bioinformatics↗

bioRxiv2019

Comparative genomics groups phages of Negativicutes and classical Firmicutes despite different Gram-staining properties

Negativicutes are Gram-Negative bacteria characterized by two cell membranes, but they are phylogenetically a side-branch of Gram-Positive Firmicutes that contain only a single membrane. We asked whether viruses (phages) infecting Negativicutes were horizontally acquired from Gram-Negative Proteobacteria, given the shared outer cell structure of their bacterial hosts, or if Negativicute phages co-evolved vertically with their hosts and thus resemble Gram-Positive Firmicute prophages. We predicted and characterised 485 prophages from Gram-Negative Firmicute genomes plus 2,977 prophages from other bacterial clades, and we used virome sequence data from 183 human stool samples to provide independent evidence for our predictions. The majority of the identified Negativicute prophages were lambdoids closer related to prophages from other Firmicutes than Proteobacteria by sequence relationship and genome organization (position of the lysis module). Only a single Mu-like candidate prophage and no clear P2-like prophages were identified in Negativicutes, both commonly found in Proteobacteria. Therefore, it is unlikely that Negativicute phages were acquired from Proteobacteria. Sequence-related prophages were identified in two distinct Negativicute orders (Veillonellales and Acidaminococcales) possibly suggesting horizontal cross-order phage infection between human gut commensals. Phages infecting these Negativicute orders occasionally harboured putative antibiotic resistance genes.

microbiology↗

bioRxiv2019

The genome of the blind soil-dwelling and ancestrally wingless dipluran Campodea augens, a key reference hexapod for studying the emergence of insect innovations

The dipluran two-pronged bristletail Campodea augens is a blind ancestrally wingless hexapod with the remarkable capacity to regenerate lost body appendages such as its long antennae. As sister group to Insecta (sensu stricto), Diplura are key to understanding the early evolution of hexapods and the origin and evolution of insects. Here we report the 1.2-Gbp draft genome of C. augens and results from comparative genomic analyses with other arthropods. In C. augens we uncovered the largest chemosensory gene repertoire of ionotropic receptors in the animal kingdom, a massive expansion which might compensate for the loss of vision. We found a paucity of photoreceptor genes mirroring at the genomic level the secondary loss of an ancestral external photoreceptor organ. Expansions of detoxification and carbohydrate metabolism gene families might reflect adaptations for foraging behaviour, and duplicated apoptotic genes might underlie its high regenerative potential.\n\nThe C. augens genome represents one of the key references for studying the emergence of genomic innovations in insects, the most diverse animal group, and opens up novel opportunities to study the under-explored biology of diplurans.

genomics↗

bioRxiv2018

LEMMI: A Live Evaluation of Computational Methods for Metagenome Investigation

Studies of microbiomes are booming, as well as the diversity of computational tools to make sense out of the sequencing data and the volumes of accumulated microbial genotypes. LEMMI (https://lemmi.ezlab.org) is a novel concept of a benchmarking platform of computational tools for metagenome composition assessments that introduces: a continuous integration of tools, their multi-objective ranking, and an effective distribution through software containers. Here, we detail the workflow and discuss the evaluation of some recently released methods. We see this platform eventually as a community-driven effort: where method developers can showcase novel approaches and get unbiased benchmarks for publications, while users can make informed choices and obtain standardized and easy-to-use tools.

microbiology↗

bioRxiv2017

ACI-1 class A beta-lactamase is widespread across human gut microbiomes due to transposons harboured by tailed prophages

Antibiotic resistance is increasing among pathogens at unprecedented rates and the human body contains a large pool of antibiotic resistance genes that can be spread among bacteria by mobile genetic elements. Acidaminococcus intestini, a bacterium found in the human gut that belongs to the class of Negativicutes, is the first gram-negative coccus shown to be resistant to beta-lactam antibiotics. Resistance is conferred by aci1, a gene encoding the ACI-1 class A beta-lactamase, but the evolutionary history of aci1 and its distribution across other Negativicutes and in the human gut microbiota remains obscure. We discovered that ACI-1 proteins are phylogenetically distinct from class A beta-lactamases of gram-positive Firmicutes and that the aci1 gene occurs in bacteria scattered across the Negativicutes clade, suggesting possible mobilization. In the reference A. intestini RyC-MR95 strain, we found that aci1 is surrounded by mobile DNA, transposon derived sequences directly flank aci1 and are likely the vehicle for its mobility. These transposon sequences reside within a prophage context consisting of two likely degraded tailed prophages, the first prophages to be characterised in A. intestini. We found aci1 in at least 56 (4.4%) out of 1,267 human gut metagenome samples, mostly hosted within A. intestini, and, where could be determined, mostly within a similar constellation of mobile elements to that found in the reference A. intestini genome. These human samples are from individuals in Europe, China and the USA, showing that aci1 is widely distributed globally. Additionally, we examined the nine different Negativicute genome assemblies that contain aci1, and found that only two of these strains show a similar mobile element context around aci1 to the reference A. intestini with transposons adjacent to a tailed prophage. However, in all nine cases aci1 is flanked by transposon derived sequences, and these sequences are diverse, suggesting the activity and degradation of multiple transposons. Overall, we show that ACI-1 proteins form a distinct class A beta lactamase family, and that the aci1 gene is present in human guts worldwide within Negativicute bacterial hosts, due to transposons, sometimes inserted into tailed prophages.

microbiology↗