Biology subjects

Montoya, D.

Publications and source records attributed to Montoya, D..

5 recordsLinked to original sources

bioRxiv2018

Dual RNAseq of human leprosy lesions identifies bacterial determinants linked to host immune response

To understand how the interaction between an intracellular bacterium and the host immune system contributes to outcome at the site of infection, we studied leprosy, a disease that forms a clinical spectrum, in which progressive infection by the intracellular bacterium Mycobacterium leprae is characterized by the production of type | IFNs and antibody production. We performed dual RNAseq on patient lesions, identifying a continuum of distinct bacterial states that are linked to the host immune response. The bacterial burden, represented by the fraction of bacterial transcripts, correlates with a host type | IFN gene signature, known to inhibit antimicrobial responses. Second, the bacterial transcriptional activity, defined by the bacterial mRNA/rRNA ratio, links bacterial heat shock proteins with the BAFF-BCMA host antibody response pathway. Our findings provide a platform for interrogation of host and pathogen transcriptomes at the site of infection, allowing insight into mechanisms of inflammation in human disease.

microbiology↗

bioRxiv2018

Trade-offs in provisioning and stability of multiple ecosystem services in agroecosystems

Changes in land use generate trade-offs in the delivery of ecosystem services in agricultural landscapes. However, we know little about how the stability of ecosystem services responds to landscape composition, and what ecological mechanisms underlie these trade-offs. Here, we develop a model to investigate the dynamics of three ecosystem services in intensively-managed agroecosystems, i.e. pollination-independent crop yield, crop pollination, and biodiversity. Our model reveals trade-offs and synergies imposed by landscape composition that affect not only the magnitude but also the stability of ecosystem service delivery. Trade-offs involving crop pollination are strongly affected by the degree to which crops depend on pollination and by their relative requirement for pollinator densities. We show conditions for crop production to increase with biodiversity and decreasing crop area, reconciling farmers profitability and biodiversity conservation. Our results further suggest that, for pollination-dependent crops, management strategies that focus on maximising yield will often overlook its stability. Given that agriculture has become more pollination-dependent over time, it is essential to understand the mechanisms driving these trade-offs to ensure food security.

ecology↗

bioRxiv2017

A Phylogenomic Study Quantifies Competing Mechanisms for Pseudogenization in Prokaryotes

BackgroundPseudogenes are non-functional sequences in the genome with homologous sequences that are functional (i.e. genes). They are abundant in eukaryotes where they have been extensively investigated, while in prokaryotes they are significantly scarcer and less well studied. Here we conduct a comprehensive analysis of the evolution of pseudogenes in prokaryotes. For this analysis we consider a broad range of bacteria, but also focus on the leprosy pathogen Mycobacterium leprae, which contains an unusually large number of pseudogenes which comprise approximately 40% of its entire genome.\n\nResultsWe have developed an informatics-based approach to characterize the evolution of pseudogenes. This approach combines tools from phylogenomics, genomics, and transcriptomics. The results we obtain suggest the presence of two mechanisms for pseudogene formation: failed horizontal gene transfer events and disruption of native genes.\n\nConclusionsWe conclude that while in most bacteria the former is most likely responsible for the majority of pseudogenization events, in mycobacteria, and in particular in M. leprae with its exceptionally high pseudogene numbers, the latter predominates. We believe that our study sheds new light on the evolution of pseudogenes in bacteria, by utilizing new methodologies that are applied to the unusually abundant M. leprae pseudogenes and their orthologs. As such, we anticipate that it will be of broad interest to both evolutionary biologists as well as microbiologists.

evolutionary biology↗

bioRxiv2017

Epigenome-wide association in adipose tissue from the METSIM cohort identifies novel loci and the involvement of adipocytes and macrophages in diabetes traits

Most epigenome-wide association studies to date have been conducted in blood. However, metabolic syndrome is mediated by a dysregulation of adiposity and therefore it is critical to study adipose tissue in order to understand the effects of this syndrome on epigenomes. To determine if natural variation in DNA methylation was associated with metabolic syndrome traits, we profiled global methylation levels in subcutaneous abdominal adipose tissue. We measured association between 32 clinical traits related to diabetes and obesity in 201 people from the Metabolic Syndrome In Men cohort. We performed epigenome-wide association studies between DNA methylation levels and traits, and identified associations for 13 clinical traits in 21 loci. We prioritized candidate genes in these loci using eQTL, and identified 18 high confidence candidate genes, including known and novel genes associated with diabetes and obesity traits. Using methylation deconvolution, we examined which cell types may be mediating the associations, and concluded that most of the loci we identified were specific to adipocytes. We determined whether the abundance of cell types varies with metabolic traits, and found that macrophages increased in abundance with the severity of metabolic syndrome traits. Finally, we developed a DNA methylation based biomarker to assess type II diabetes risk in adipose tissue. In conclusion, our results demonstrate that profiling DNA methylation in adipose tissue is a powerful tool for understanding the molecular effects of metabolic syndrome on adipose tissue, and can be used in conjunction with traditional genetic analyses to further characterize this disorder.

genetics↗

bioRxiv2016

Profiling adaptive immune repertoires across multiple human tissues by RNA Sequencing

Assay-based approaches provide a detailed view of the adaptive immune system by profiling T and B cell receptor repertoires. However, these methods come at a high cost and lack the scale of standard RNA sequencing (RNA-seq). Here we report the development of ImReP, a novel computational method for rapid and accurate profiling of the adaptive immune repertoire from regular RNA-Seq data. We applied it to 8,555 samples across 544 individuals from 53 tissues from the Genotype-Tissue Expression (GTEx v6) project. ImReP is able to efficiently extract TCR- and BCR- derived reads from the RNA-Seq data and accurately assemble the complementarity determining regions 3 (CDR3s), the most variable regions of B- and T-cell receptors determining their antigen specificity. Using ImReP, we have created the systematic atlas of immunological sequences for B- and T-cell repertoires across a broad range of tissue types, most of which have not been studied for B and T cell receptor repertoires. We have also examined the compositional similarities of clonal populations between the GTEx tissues to track the flow of T- and B- clonotypes across immune-related tissues, including secondary lymphoid organs and organs encompassing mucosal, exocrine, and endocrine sites. The atlas of T- and B-cell receptor receptors, freely available at https://sergheimangul.wordpress.com/atlas-immune-repertoires/, is the largest collection of CDR3 sequences and tissue types. We anticipate this recourse will enhance future studies in areas such as immunology and advance development of therapies for human diseases. ImReP is freely available at https://sergheimangul.wordpress.com/imrep/.

immunology↗