一篇單細胞和WGCNA結合的文獻解讀-1

文章題目

Single Cell Gene Co-Expression Network Reveals FECH/CROT Signature as a Prognostic Marker

背景知識

AR（Androgen receptor蛛淋，雄激素受體）活性的增加驅動晚期前列腺癌的治療耐藥环形，深入剖析AR調控網(wǎng)絡的機制至關重要请唱。GCN（co-expression network）有助于成功識別AR變量驅動的基因模塊，但是由于GCN的高度稀疏性和維數(shù)高善炫，為所有被檢測基因構建的GCN太大而無法解釋着绷。而加權相關網(wǎng)絡分析(WGCNA)利用層次聚類方法識別基因簇，并能提取潛在表型的有意義的生物信息拯辙。近期研究表明LNCaP細胞對雄激素剝奪治療反應不一〗宋現(xiàn)已發(fā)現(xiàn)雄激素剝奪治療的耐藥亞群，其特征是細胞周期活動增強环壤。因此晒来，本研究旨在從單細胞的角度找出AR調控的關鍵生物學過程及其雄激素調控基因。

==androgen（R1881）==郑现，也被稱為甲基三烯醇湃崩，是一種合成的雄激素。它是AR激動劑接箫。

biomodal：雙峰性表達攒读，描述如下圖

image-20200601113642215

BI value:BI index,用來代表 biomodal expression的extent，The bimodality index (BI) is used to distribution of marker genes (AR, KLK3, and TMPRSS2) in single cells; Genes with BI > 1.2 are regarded as bimodally expressed genes

材料方法

數(shù)據(jù)：We downloaded the processed expression (RPKM) profiles of LNCaP cells generated by single cell RNA-seq from GEO (accession ID: GSE99795). The dataset contains 144 LNCaP cells from 0 h untreated, 12 h untreated and 12 h R1881 treated conditions. There are 48 cells under each condition.

Bimodality expression was performed using the ==R package, SIBER== . First, a normal mixture model (‘NL’) was specified on the log2 transformed RPKM expression values to fit the gene expression distribution into a two component mixture model (component 1 and 2). Next the average values (mu1 and mu2) were calculated. Other parameters were also obtained including variance values (sigma1, sigma2) and corresponding proportion of the component 1 and 2 (pi1 and pi2).

結果

結果1.我們嘗試用雙峰表達模式來表征細胞的異質性辛友。

作者研究了已知的ARGs薄扁，如KLK3和TMPRSS2的表達

image-20200601112841618

image-20200601114836790

結果2.WGCNA

he gene expression profiles, comprising of 10,445 genes in 144 samples, were log2 transformed and subjected to WGCNA.

image-20200601113020409

結果3.確定由AR調控的模塊

已有研究表明由AR調控的DEGS-共272個，現(xiàn)在看哪些模塊與這272個DEGs 重疊性最高废累。黃色和紅色模塊中的基因與來自單細胞RNA-seq數(shù)據(jù)集的ARGs明顯重疊

image-20200601113404534

結果4. 由AR受體調控的 Biological Functions of Modules

Because the bimodal gene expression commonly existed of function enrichment is shown in Figure 4A. Because the bimodal gene expression commonly among single cells (Figure 1), we aimed to find the function terms that showed most expressed pattern. The average_BI value (Figure 4A) for a function term is the average BI of module bimodally express.主要是generation of precursor metabolites and energy這個通路

==應用的包是RobustRankaAggreg==

image-20200601114617483

Jiang et al. developed the androgen responsive gene database (ARGDB) to provide integrated knowledge on androgen-controlled genes .Among these 11 genes, FECH and CROT are novel androgen regulated genes according to ARGDB.
兩種基因FECH是非雙峰性基因邓梅，BI值小于1.2，而CHOT是雙峰性基因邑滨，BI值大于1.2
image-20200601115759420