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Manni, M.

Publications and source records attributed to Manni, M..

9 recordsLinked to original sources

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↗

Extracellular matrix educates a tumor macrophage phenotype found in ovarian cancer metastasis

Recent studies have shown the tumor extracellular matrix (ECM) associates with immunosuppression, and that targeting the ECM can improve immune infiltration and immunotherapy response. A question that remains is whether the ECM is directly educating the immune phenotypes seen in cancer. We identified a tumor-associated macrophage (TAM) population correlated with poor prognosis, interruption of the cancer immunity cycle, and tumor ECM composition. To investigate whether ECM was capable of generating the TAM phenotype seen, we developed a decellularized tissue model that retains the native ECM architecture and composition. Macrophages cultured on decellularized ovarian metastasis shared transcriptional profiles with the TAMs found in human tissues. ECM educated macrophages have a tissue remodeling and immunoregulatory phenotype, inducing altered T cell function. We conclude that the tumor ECM is directly educating this macrophage population found in cancer tissues. Therefore, current and emerging cancer therapies that target the tumor ECM may be tailored to improve macrophage phenotype and their downstream regulation of immunity.

cancer biology↗

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↗

Sex-specific differences in the function and differentiation of ABCsmark TLR7-driven immunopathogenesis

Sex differences characterize immune responses to viruses and autoimmune diseases like SLE. ABCs are an emerging population of CD11c+ T-bet+ B cells critical for antiviral responses and autoimmune disorders. DEF6 and SWAP70, are two homologous molecules whose combined absence in double-knock-out mice (DKOs) leads to a lupus syndrome in females marked by an accumulation of ABCs. Here we demonstrate that DKO ABCs exhibit sex-specific differences in their expansion, upregulation of an ISG signature, and further differentiation. BCR sequencing and fate mapping experiments reveal that DKO ABCs undergo oligoclonal expansion and differentiate into both CD11c+ and CD11c- effector populations with pathogenic and proinflammatory potential. Tlr7 duplication in DKO males overrides the sex-bias and further augments the dissemination and pathogenicity of ABCs resulting in severe pulmonary inflammation and early mortality. Thus, sexual dimorphism shapes the expansion, function, and differentiation of ABCs contributing to the sex-bias that accompanies TLR7-driven immunopathogenesis.

immunology↗

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↗

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↗

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↗

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↗

BUSCO applications from quality assessments to gene prediction and phylogenomics

Genomics promises comprehensive surveying of genomes and metagenomes, but rapidly changing technologies and expanding data volumes make evaluation of completeness a challenging task. Technical sequencing quality metrics can be complemented by quantifying completeness in terms of the expected gene content of Benchmarking Universal Single-Copy Orthologs (BUSCO, http://busco.ezlab.org). Now in its third release, BUSCO utilities extend beyond quality control to applications in comparative genomics, gene predictor training, metagenomics, and phylogenomics.

bioinformatics↗