International Journal of Molecular Sciences

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Dear Colleagues,

Infectious diseases are still a major public health problem today. Now, deciphering the pathogenic process is a challenge which is facilitated by the development of new high throughput technologies. Only omics approaches can achieve this goal. Each of these approaches brings its own data stream on infectious diseases. A systemic integration of these omics data enables results to be closer to reality. All these large-scale studies should eventually lead to the identification of biomarkers useful in both diagnosis and prognosis. It should also lead to the identification of new therapeutic targets and the development of new drugs. Finally, it is hoped that these approaches will lead to better patient management. This Special Issue is focusing on the various omics approaches taken separately or combined.

Dr. Christophe Chevillard
Guest Editor

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Keywords

infectious disease
genetics
epigenetics
methylation
proteomic
metabolomic
systemic integration
biomarkers
drugs development

Published Papers (2 papers)

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Research

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17 pages, 825 KiB

Open AccessArticle

Genome-Wide Meta-Analysis Identifies Multiple Novel Rare Variants to Predict Common Human Infectious Diseases Risk

by Andrea Gelemanović, Tatjana Ćatipović Ardalić, Ajka Pribisalić, Caroline Hayward, Ivana Kolčić and Ozren Polašek

Int. J. Mol. Sci. 2023, 24(8), 7006; https://doi.org/10.3390/ijms24087006 - 10 Apr 2023

Cited by 2 | Viewed by 1604

Abstract

Infectious diseases still threaten global human health, and host genetic factors have been indicated as determining risk factors for observed variations in disease susceptibility, severity, and outcome. We performed a genome-wide meta-analysis on 4624 subjects from the 10,001 Dalmatians cohort, with 14 infection-related traits. Despite a rather small number of cases in some instances, we detected 29 infection-related genetic associations, mostly belonging to rare variants. Notably, the list included the genes CD28, INPP5D, ITPKB, MACROD2, and RSF1, all of which have known roles in the immune response. Expanding our knowledge on rare variants could contribute to the development of genetic panels that could assist in predicting an individual’s life-long susceptibility to major infectious diseases. In addition, longitudinal biobanks are an interesting source of information for identifying the host genetic variants involved in infectious disease susceptibility and severity. Since infectious diseases continue to act as a selective pressure on our genomes, there is a constant need for a large consortium of biobanks with access to genetic and environmental data to further elucidate the complex mechanisms behind host–pathogen interactions and infectious disease susceptibility. Full article

(This article belongs to the Special Issue Genetics, Epigenetics, Proteomics and Functional Genomic Approaches in Infectious Diseases)

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9 pages, 635 KiB

Open AccessBrief Report

Parasite DNA and Markers of Decreased Immune Activation Associate Prospectively with Cardiac Functional Decline over 10 Years among Trypanosoma cruzi Seropositive Individuals in Brazil

by Ashwin Sunderraj, Luisa Marin Cunha, Matheus Avila, Shaina Alexandria, Ariela Mota Ferreira, Léa Campos de Oliveira-da Silva, Antonio L. P. Ribeiro, Maria do Carmo Pereira Nunes, Ester C. Sabino, Alan Landay, Jorge Kalil, Christophe Chevillard, Edecio Cunha-Neto and Matthew J. Feinstein

Int. J. Mol. Sci. 2024, 25(1), 44; https://doi.org/10.3390/ijms25010044 - 19 Dec 2023

Cited by 1 | Viewed by 836

Abstract

Parasitemia and inflammatory markers are cross-sectionally associated with chronic Chagas cardiomyopathy (CCC) among patients with Trypanosoma cruzi. However, the prospective association of the parasite load and host immune response-related characteristics with CCC (that is, progressors) among T. cruzi seropositive individuals has only been partially defined. In a cohort of T. cruzi seropositive patients in Montes Claros and São Paulo, Brazil who were followed over 10 years, we identified the association of a baseline T. cruzi parasite load and systemic markers of inflammation with a decline in cardiac function and/or the presence of cardiac congestion 10 years later. The progressors (n = 21) were individuals with a significant decline in the left ventricular ejection fraction and/or elevated markers of cardiac congestion after 10 years. The controls (n = 31) had normal markers of cardiac function and congestion at the baseline and at the follow-up. They were matched with the progressors on age, sex, and genetic ancestry. The progressors had higher mean parasite loads at the baseline than the controls (18.3 vs. 0.605 DNA parasite equivalents/20 mL, p < 0.05). Of the 384 inflammation-related proteins analyzed, 47 differed significantly at a false discovery rate- (FDR-) corrected p < 0.05 between the groups. There were 44 of these 47 proteins that were significantly higher in the controls compared to in the progressors, including the immune activation markers CCL21, CXCL12, and HCLS1 and several of the tumor necrosis factor superfamily of proteins. Among the individuals who were seropositive for T. cruzi at the baseline and who were followed over 10 years, those with incident CCC at the 10-year marker had a comparatively higher baseline of T. cruzi parasitemia and lower baseline markers of immune activation and chemotaxis. These findings generate the hypothesis that the early impairment of pathogen-killing immune responses predisposes individuals to CCC, which merits further study. Full article

(This article belongs to the Special Issue Genetics, Epigenetics, Proteomics and Functional Genomic Approaches in Infectious Diseases)

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