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      Plasma MicroRNA Profiling of Plasmodium falciparum Biomass and Association with Severity of Malaria Disease

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          Abstract

          Severe malaria (SM) is a major public health problem in malaria-endemic countries. Sequestration of Plasmodium falciparum–infected erythrocytes in vital organs and the associated inflammation leads to organ dysfunction. MicroRNAs (miRNAs), which are rapidly released from damaged tissues into the host fluids, constitute a promising biomarker for the prognosis of SM. We applied next-generation sequencing to evaluate the differential expression of miRNAs in SM and in uncomplicated malaria (UM) in children in Mozambique. Six miRNAs were associated with in vitro P. falciparum cytoadhesion, severity in children, and P. falciparum biomass. Relative expression of hsa-miR-4497 quantified by TaqMan-quantitative reverse transcription PCR was higher in plasma of children with SM than those with UM (p<0.048) and again correlated with P. falciparum biomass (p = 0.033). These findings suggest that different physiopathological processes in SM and UM lead to differential expression of miRNAs and suggest a pathway for assessing their prognostic value malaria.

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          Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2

          Michael Love, Wolfgang Huber, Simon Anders (2014)
          In comparative high-throughput sequencing assays, a fundamental task is the analysis of count data, such as read counts per gene in RNA-seq, for evidence of systematic changes across experimental conditions. Small replicate numbers, discreteness, large dynamic range and the presence of outliers require a suitable statistical approach. We present DESeq2, a method for differential analysis of count data, using shrinkage estimation for dispersions and fold changes to improve stability and interpretability of estimates. This enables a more quantitative analysis focused on the strength rather than the mere presence of differential expression. The DESeq2 package is available at http://www.bioconductor.org/packages/release/bioc/html/DESeq2.html. Electronic supplementary material The online version of this article (doi:10.1186/s13059-014-0550-8) contains supplementary material, which is available to authorized users.
          Article 0 comments Cited 25441 times – based on 0 reviews     Review now
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            Circulating microRNAs as stable blood-based markers for cancer detection.

            P. S. Mitchell, R. K. Parkin, E. Kroh … (2008)
            Improved approaches for the detection of common epithelial malignancies are urgently needed to reduce the worldwide morbidity and mortality caused by cancer. MicroRNAs (miRNAs) are small ( approximately 22 nt) regulatory RNAs that are frequently dysregulated in cancer and have shown promise as tissue-based markers for cancer classification and prognostication. We show here that miRNAs are present in human plasma in a remarkably stable form that is protected from endogenous RNase activity. miRNAs originating from human prostate cancer xenografts enter the circulation, are readily measured in plasma, and can robustly distinguish xenografted mice from controls. This concept extends to cancer in humans, where serum levels of miR-141 (a miRNA expressed in prostate cancer) can distinguish patients with prostate cancer from healthy controls. Our results establish the measurement of tumor-derived miRNAs in serum or plasma as an important approach for the blood-based detection of human cancer.
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              Distribution of miRNA expression across human tissues

              Nicole Ludwig, Petra Leidinger, Kurt Becker … (2016)
              We present a human miRNA tissue atlas by determining the abundance of 1997 miRNAs in 61 tissue biopsies of different organs from two individuals collected post-mortem. One thousand three hundred sixty-four miRNAs were discovered in at least one tissue, 143 were present in each tissue. To define the distribution of miRNAs, we utilized a tissue specificity index (TSI). The majority of miRNAs (82.9%) fell in a middle TSI range i.e. were neither specific for single tissues (TSI > 0.85) nor housekeeping miRNAs (TSI < 0.5). Nonetheless, we observed many different miRNAs and miRNA families that were predominantly expressed in certain tissues. Clustering of miRNA abundances revealed that tissues like several areas of the brain clustered together. Considering -3p and -5p mature forms we observed miR-150 with different tissue specificity. Analysis of additional lung and prostate biopsies indicated that inter-organism variability was significantly lower than inter-organ variability. Tissue-specific differences between the miRNA patterns appeared not to be significantly altered by storage as shown for heart and lung tissue. MiRNAs TSI values of human tissues were significantly (P = 10−8) correlated with those of rats; miRNAs that were highly abundant in certain human tissues were likewise abundant in according rat tissues. We implemented a web-based repository enabling scientists to access and browse the data (https://ccb-web.cs.uni-saarland.de/tissueatlas).
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                Author and article information

                Journal
                Journal ID (nlm-ta): Emerg Infect Dis
                Journal ID (iso-abbrev): Emerg Infect Dis
                Journal ID (publisher-id): EID
                Title: Emerging Infectious Diseases
                Publisher: Centers for Disease Control and Prevention
                ISSN (Print): 1080-6040
                ISSN (Electronic): 1080-6059
                Publication date (Print): February 2021
                Volume: 27
                Issue: 2
                Pages: 430-442
                Affiliations
                [1]ISGlobal, Hospital Clinic—Universitat de Barcelona, Barcelona, Spain (H. Gupta, M. Rubio, R. Varo, P. Cisteró, A. Jimenez, X. Martiáñez-Vendrell, D. Barrios, A. Brimacombe, M. Bustamante, Q. Bassat, A. Mayor);
                [2]Centro de Investigação em Saúde de Manhiça (CISM), Maputo, Mozambique (A. Sitoe, R. Varo, L. Madrid, I. Cuamba, Q. Bassat, A. Mayor);
                [3]Spanish Consortium for Research in Epidemiology and Public Health (CIBERESP), Madrid, Spain (A. Jimenez, M. Bustamante, Q. Bassat, A. Mayor);
                [4]Harvard T.H. Chan School of Public Health Department of Biostatistics, Boston, Massachusetts, USA (L. Pantano);
                [5]Universitat Pompeu Fabra (UPF), Barcelona (M. Bustamante); I
                [6]nstitut Català de Recerca en Estudis Avançats (ICREA), Barcelona (Q. Bassat);
                [7]Hospital Sant Joan de Déu—University of Barcelona Pediatrics Department, Barcelona (Q. Bassat)
                Author notes
                Address for correspondence: Himanshu Gupta, ISGlobal, Hospital Clínic, Universitat de Barcelona, Carrer Rosselló 153 (CEK Bldg), E-08036 Barcelona, Spain; email: himanshu.gupta@ 123456isglobal.org or himanshugupta.hcu@ 123456gmail.com
                Article
                Publisher ID: 19-1795
                DOI: 10.3201/eid2702.191795
                PMC ID: 7853565
                PubMed ID: 33496227
                SO-VID: b567419d-57cd-4390-a77e-ce0b7a184f36
                History
                Categories
                Subject: Research
                Subject: Research
                Subject: Plasma MicroRNA Profiling of Plasmodium falciparum Biomass and Association with Severity of Malaria Disease

                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: plasmodium falciparum,mirna,malaria,severe malaria,biomarkers,next-generation sequencing,histidine-rich protein 2,vector-borne infections,mozambique,parasites,spain
                Data availability:
                ScienceOpen disciplines: Infectious disease & Microbiology
                Keywords: plasmodium falciparum, mirna, malaria, severe malaria, biomarkers, next-generation sequencing, histidine-rich protein 2, vector-borne infections, mozambique, parasites, spain

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