RNA sequencing data from neutrophils of patients with cystic fibrosis reveals potential for developing biomarkers for pulmonary exacerbations.
RNA sequencing data from neutrophils of patients with cystic fibrosis reveals potential for developing biomarkers for pulmonary exacerbations.
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DOI：
10.1016/j.jcf.2018.05.014
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发表时间：
2019-03
期刊：
影响因子：
--
通讯作者：
Jarvis JN
中科院分区：
文献类型：
--
作者：
Jiang K;Poppenberg KE;Wong L;Chen Y;Borowitz D;Goetz D;Sheehan D;Frederick C;Tutino VM;Meng H;Jarvis JN
目前还没有有效的方法在囊性纤维化(CF)肺加重(CFPE)出现症状之前预测它们或评估满意的治疗反应。CFPE治疗前后患者外周血中性粒细胞的RNA测序被用来创建转录组图谱。在余弦K近邻(KNN)模型中使用平均转录水平(TPM)为1.0和错误发现率(FDR)为0.05的转录本。实时定量聚合酶链式反应证实了来自一组独立的CF患者的中性粒细胞和全血样本中的RNA测序表达差异。采用双抗体夹心ELISA法检测CF患者治疗前后血浆MRP8/14复合体水平。当我们比较治疗前后CF患者的中性粒细胞时，我们发现了136个转录本和83个亚型的差异表达(>；1.5倍变化，FDR调整P<；0.05)。该模型能够成功地从相同的恢复期患者身上分离出CF耀斑样本，在训练和测试队列中的准确率均为0.75。用分离的中性粒细胞和一组独立的CF患者的全血进行实时荧光定量聚合酶链式反应(Real Time PCR)证实了6个差异表达的基因，尽管治疗前后CF患者血浆中髓系相关蛋白MRP8/14二聚体的水平基本没有变化。我们的发现证明了机器学习方法对疾病状态进行分类的潜力，从而开发出可用于监测CF肺部疾病活动的敏感生物标记物。
There is no effective way to predict cystic fibrosis (CF) pulmonary exacerbations (CFPE) before they become symptomatic or to assess satisfactory treatment responses. RNA sequencing of peripheral blood neutrophils from CF patients before and after therapy for CFPE was used to create transcriptome profiles. Transcripts with an average transcripts per million (TPM) level>1.0 and a false discovery rate (FDR)<0.05 were used in a cosine K-nearest neighbor (KNN) model. Real time PCR was used to corroborate RNA sequencing expression differences in both neutrophils and whole blood samples from an independent cohort of CF patients. Furthermore, sandwich ELISA was conducted to assess plasma levels of MRP8/14 complexes in CF patients before and after therapy. We found differential expression of 136 transcripts and 83 isoforms when we compared neutrophils from CF patients before and after therapy (>1.5 fold change, FDR-adjusted P< 0.05). The model was able to successfully separate CF flare samples from those taken from the same patients in convalescence with an accuracy of 0.75 in both the training and testing cohorts. Six differently expressed genes were confirmed by real time PCR using both isolated neutrophils and whole blood from an independent cohort of CF patients before and after therapy, even though levels of myeloid related protein MRP8/14 dimers in plasma of CF patients were essentially unchanged by therapy. Our findings demonstrate the potential of machine learning approaches for classifying disease states and thus developing sensitive biomarkers that can be used to monitor pulmonary disease activity in CF.
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影响因子：
3.7
作者：
Conese M;Castellani S;Lepore S;Palumbo O;Manca A;Santostasi T;Polizzi AM;Copetti M;Di Gioia S;Casavola V;Guerra L;Diana A;Montemurro P;Mariggiò MA;Gallo C;Maffione AB;Carella M
通讯作者：
Carella M
影响因子：
3.1
作者：
Downey, Damian G.;Brockbank, Simon;Elborn, J. Stuart
通讯作者：
Elborn, J. Stuart
影响因子：
11.1
作者：
Boucher, R. C.
通讯作者：
Boucher, R. C.
影响因子：
14.9
作者：
Dozmorov, I;Knowlton, N;Centola, M
通讯作者：
Centola, M
DOI：
10.1007/978-1-60761-580-4_15
发表时间：
2010-01-01
期刊：
STATISTICAL METHODS IN MOLECULAR BIOLOGY
影响因子：
--
作者：
Deng, Xutao;Campagne, Fabien
通讯作者：
Campagne, Fabien