Biology subjects

Blanco-Miguez, A.

Publications and source records attributed to Blanco-Miguez, A..

5 recordsLinked to original sources

bioRxiv2024

Discovering and exploring the hidden diversity of human gut viruses using highly enriched virome samples

Viruses are an abundant and crucial component of the human microbiome, but accurately discovering them via metagenomics is still challenging. Currently, the available viral reference genomes poorly represent the diversity in microbiome samples, and expanding such a set of viral references is difficult. As a result, many viruses are still undetectable through metagenomics even when considering the power of de novo metagenomic assembly and binning, as viruses lack universal markers. Here, we describe a novel approach to catalog new viral members of the human gut microbiome and show how the resulting resource improves metagenomic analyses. We retrieved >3,000 viral-like particles (VLP) enriched metagenomic samples (viromes), evaluated the efficiency of the enrichment in each sample to leverage the viromes of highest purity, and applied multiple analysis steps involving assembly and comparison with hundreds of thousands of metagenome-assembled genomes to discover new viral genomes. We reported over 162,000 viral sequences passing quality control from thousands of gut metagenomes and viromes. The great majority of the retrieved viral sequences ([~]94.4%) were of unknown origin, most had a CRISPR spacer matching host bacteria, and four of them could be detected in >50% of a set of 18,756 gut metagenomes we surveyed. We included the obtained collection of sequences in a new MetaPhlAn 4.1 release, which can quantify reads within a metagenome matching the known and newly uncovered viral diversity. Additionally, we released the viral database for further virome and metagenomic studies of the human microbiome.

microbiology↗

bioRxiv2022

Extending and improving metagenomic taxonomic profiling with uncharacterized species with MetaPhlAn 4

Metagenomic assembly enables novel organism discovery from microbial communities, but from most metagenomes it can only capture few abundant organisms. Here, we present a method - MetaPhlAn 4 - to integrate information from both metagenome assemblies and microbial isolate genomes for improved and more comprehensive metagenomic taxonomic profiling. From a curated collection of 1.01M prokaryotic reference and metagenome-assembled genomes, we defined unique marker genes for 26,970 species-level genome bins, 4,992 of them taxonomically unidentified at the species level. MetaPhlAn 4 explains [~]20% more reads in most international human gut microbiomes and >40% in less-characterized environments such as the rumen microbiome, and proved more accurate than available alternatives on synthetic evaluations while also reliably quantifying organisms with no cultured isolates. Application of the method to >24,500 metagenomes highlighted previously undetected species to be strong biomarkers for host conditions and lifestyles in human and mice microbiomes, and showed that even previously uncharacterized species can be genetically profiled at the resolution of single microbial strains. MetaPhlAn 4 thus integrates the novelty of metagenomic assemblies with the sensitivity and fidelity of reference-based analyses, providing efficient metagenomic profiling of uncharacterized species and enabling deeper and more comprehensive microbiome biomarker detection.

bioinformatics↗

bioRxiv2021

Outer Membrane Vesicles from the gut microbiome contribute to tumor immunity by eliciting cross-reactive T cells

The gut microbiome plays a key role in cancer immunity. One proposed mechanism is through the elicitation of T cells, which incidentally recognize neo-epitopes arising from cancer mutations ("molecular mimicry (MM)" hypothesis). To support MM, Escherichia coli Nissle was engineered with the SIINFEKL epitope (OVA) and orally administered to C57BL/6 mice. The treatment elicited OVA-specific CD8+ T cells in the lamina propria and inhibited the growth of OVA-B16F10 tumors. Importantly, the administration of Outer Membrane Vesicles (OMVs) engineered with different T cell epitopes elicited epitope-specific T cells and inhibited tumor growth. Microbiome shotgun sequencing and TCR sequencing provided evidence that cross-reacting T cells were induced at the mucosal level and subsequently reached the tumor site. Overall, our data support the role of MM in tumor immunity, assign a new role to OMVs and pave the way to new probiotics/OMV-based anti-cancer immunotherapies.

microbiology↗

bioRxiv2020

Integrating taxonomic, functional, and strain-level profiling of diverse microbial communities with bioBakery 3

Culture-independent analyses of microbial communities have advanced dramatically in the last decade, particularly due to advances in methods for biological profiling via shotgun metagenomics. Opportunities for improvement continue to accelerate, with greater access to multi-omics, microbial reference genomes, and strain-level diversity. To leverage these, we present bioBakery 3, a set of integrated, improved methods for taxonomic, strain-level, functional, and phylogenetic profiling of metagenomes newly developed to build on the largest set of reference sequences now available. Compared to current alternatives, MetaPhlAn 3 increases the accuracy of taxonomic profiling, and HUMAnN 3 improves that of functional potential and activity. These methods detected novel disease-microbiome links in applications to CRC (1,262 metagenomes) and IBD (1,635 metagenomes and 817 metatranscriptomes). Strain-level profiling of an additional 4,077 metagenomes with StrainPhlAn 3 and PanPhlAn 3 unraveled the phylogenetic and functional structure of the common gut microbe Ruminococcus bromii, previously described by only 15 isolate genomes. With open-source implementations and cloud-deployable reproducible workflows, the bioBakery 3 platform can help researchers deepen the resolution, scale, and accuracy of multi-omic profiling for microbial community studies.

microbiology↗

bioRxiv2020

Release of potential pro-inflammatory peptides from SARS-CoV-2 spike glycoproteins in neutrophil-extracellular traps

COVID-2019 has progressed in around 10-15% of patients to an acute respiratory distress syndrome characterized by extensive pulmonary inflammation and elevated production of pro-inflammatory cytokines. Neutrophil activation seems to be crucial in the initiation and perpetuation of this exacerbated lung inflammation. However, the precise mechanisms by which this activation occurs remain yet elusive. To this end, this in silico study tried to identify potential proinflammatory inducing peptides (PIPs) produced by the action of the elastase released in neutrophil-extracellular traps over SARS-CoV-2 particles. We found nine potential PIPs exclusive from the SARS-CoV-2, showing homology against T cell recognition epitopes. Moreover, 78 percent of these exclusive PIPs were found produced by the enzymatic cleavage on the spike glycoproteins, suggesting that high PIP concentrations might be released following SARS-CoV-2 huge replication rate. Therefore, these PIPs might play a role in the exacerbated inflammatory response observed in some patients. HighlightsO_LINine potential PIPs were predicted exclusive from the SARS-CoV-2. C_LIO_LISARS-CoV-2 PIPs showed homology against T cell recognition epitopes. C_LIO_LIMost of PIPs were produced by enzymatic cleavage of the spike glycoproteins. C_LIO_LIThe release of these PIPs might be related to the increased inflammatory response observed in the patients. C_LI Graphical abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=189 SRC="FIGDIR/small/072439v1_ufig1.gif" ALT="Figure 1"> View larger version (49K): org.highwire.dtl.DTLVardef@1cd2c3forg.highwire.dtl.DTLVardef@113f8b7org.highwire.dtl.DTLVardef@2df78eorg.highwire.dtl.DTLVardef@1d7c946_HPS_FORMAT_FIGEXP M_FIG C_FIG

microbiology↗