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哥伦比亚一项研究中复杂疟疾的个体化转录解析

Individualized Transcriptional Resolution of Complicated Malaria in a Colombian Study.

作者信息

Rojas-Peña Mónica L, Duan Meixue, Arafat Dalia, Rengifo Lina, Herrera Socrates, Arévalo-Herrera Myriam, Gibson Greg

机构信息

Center for Integrative Genomics, Georgia Institute of Technology, Atlanta, GA 30332, USA.

CAUCASECO, Cali, Colombia.

出版信息

J Pers Med. 2018 Sep 14;8(3):29. doi: 10.3390/jpm8030029.

Abstract

To evaluate whether recovery from complicated malaria follows a common trajectory in terms of immunological mechanism or, rather, is highly individualized for each patient, we performed longitudinal gene expression profiling of whole blood. RNA sequencing (RNAseq) was performed on blood samples obtained from eight patients on four consecutive days between hospital admission and discharge. Six patients were infected with , and two with one patient was a pregnant woman infected with , who was hospitalized for several weeks. The characterization of blood transcript modules (BTM) and blood informative transcripts (BIT) revealed that patients' responses showed little commonality, being dominated by the balance of gene activity relating to lymphocyte function, inflammation, and interferon responses specific to each patient. Only weak correlations with specific complicated malaria symptoms such as jaundice, thrombocytopenia, or anemia were observed. The differential expression of individual genes, including transcripts derived from the human leukocyte antigen (HLA) complex, generally reflected differences in the underlying immune processes. Although the results of this pilot study do not point to any single process that might provide a target for complicated malaria treatment or prevention or personalized medical strategies, larger patient series and more extensive blood sampling may allow the classification of patients according to their type of response in order to develop novel therapeutic approaches.

摘要

为了评估复杂型疟疾的康复在免疫机制方面是否遵循共同轨迹,或者说是否因患者个体差异极大,我们对全血进行了纵向基因表达谱分析。在患者入院至出院期间连续四天从八名患者采集血样进行RNA测序(RNAseq)。六名患者感染了 ,两名患者感染了 ,其中一名患者是感染了 的孕妇,住院数周。血液转录模块(BTM)和血液信息转录本(BIT)的特征表明,患者的反应几乎没有共性,主要由与淋巴细胞功能、炎症以及每位患者特异性干扰素反应相关的基因活性平衡所主导。仅观察到与黄疸、血小板减少或贫血等特定复杂型疟疾症状的微弱相关性。包括源自人类白细胞抗原(HLA)复合体的转录本在内的单个基因的差异表达,通常反映了潜在免疫过程的差异。尽管这项初步研究的结果并未指向任何可能为复杂型疟疾治疗、预防或个性化医疗策略提供靶点的单一过程,但更大规模的患者队列和更广泛的血液采样可能有助于根据患者的反应类型进行分类,从而开发新的治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/83f3/6163772/c621eb46e1e7/jpm-08-00029-g001.jpg

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