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Transcriptomic-based functional characterization of adverse events following lymphatic filariasis treatment

ABSTRACT: Transcriptomic-based functional characterization of adverse events following lymphatic filariasis treatment

PROVIDER: PRJNA432948 | ENA |

REPOSITORIES: ENA

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Transcriptomic-based functional characterization of adverse events following lymphatic filariasis treatment

Project description:Intro: Lymphatic filariasis (LF) is a neglected tropical disease caused by the nematode parasite Wuchereria bancrofti. The primary tool used by the Global Program to Eliminate LF is mass drug administration (MDA), and some 500 million people take the medications each year. Mild to moderate adverse events (AEs) are common after LF treatment, and these pose a challenge for the LF elimination program. To better understand the pathogenesis of AEs, we studied patients from a LF treatment trial in Côte d’Ivoire. Method: Total RNA was extracted from peripheral blood leukocytes collected before and 24h after treatment (when AEs peak). Global RNA sequencing was performed for 9 individuals with systemic moderate AEs and for 9 matched controls without AEs. Differential gene expression analysis (DESeq) identified transcriptional signatures (TS) associated with post-treatment AEs. Results: Out of the 36 sequenced samples, the 9 post-treatment samples from subjects with AEs had a distinct TS (P=0.006 by clustering analysis); 744 genes were significantly upregulated in this group (post vs pre-treatment, paired). These genes were enriched for many biological pathways that included pro-inflammatory pathways such as TLR and NF-kappa B signaling. Genes upregulated in AEs were also significantly enriched for having STAT1/2/3 transcription factor binding sites indicating the importance for interferons in the AEs pathogenesis.

2019-08-20 | GSE110146 | GEO

Platelet proteomics profiling in transfusion adverse events

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Platelet proteomics profiling in transfusion adverse events, part 2

Project description:Blood platelets destined for transfusion release panoply of molecules during preparation and storage. The leukoreduction process made the transfusion safer but did not completely abolish the adverse events. The rationale is to study the proteome profile of platelet components PPC (platelet pellets) involved in transfusion adverse events.

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Systems analysis-based assessment of post-treatment adverse events in lymphatic filariasis.

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Transcription profiling of of the human filarial nematode Brugia malayi across multiple life-cycle stages

Project description:High-throughput sequencing to profile the transcriptome of the human filarial nematode Brugia malayi, the causative agent of lymphatic filariasis, across multiple life-cycle stages.

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Adverse Events of anti-EGFR Therapy are Triggered by Hair Eruption and Commensal Skin Microbiota

Project description:Adverse Events of anti-EGFR Therapy are Triggered by Hair Eruption and Commensal Skin Microbiota

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Wuchereria bancrofti strain:NA

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Qualitative and label-free quantitative analysis of protein changes in the lymphatic muscle cells isolated in a hind-limb lymphatic injury model in the sheep

Project description:We developed a large animal model, with clinically relevant gravitational loading on the lymphatic vasculature, that enables longitudinal tracking of lymphatic function in vivo as well as end-point analysis of vessel function and mechanics. One of two parallel lymphatic vessels in the sheep hind limb was ligated with the contralateral limb acting as an internal control. To determine the changes in the protein expression profiles in the lymphatic muscle cells from the remodeled vessel compared to the control, we expanded isolated LMC in vitro and performed bottom-up proteomic analysis using a Q Exactive Plus mass spectrometer. Label-free quantitative (LFQ) methods directly used the raw spectral data from parallel MS runs to determine relative protein abundances. We used both “MS/MS (MS2) spectral counting” and “precursor MS1 area” methods for label free quantitation and further contrasting the differentially expressed proteomic profiles across the control and remodeled lymphatic muscle samples to determine the alterations in mitochondrial dysfunction and elevated oxidative stress within the lymphatic muscle.

2021-01-12 | PXD014343 | Pride

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