了解人類中樞神經(jīng)系統(tǒng)(CNS)細(xì)胞識別的分子基礎(chǔ)對于確定不同細(xì)胞類型的功能及其對不同病理的敏感性至關(guān)重要怕敬。由于基因表達(dá)位于細(xì)胞同一性的根源，人類中樞神經(jīng)系統(tǒng)轉(zhuǎn)錄組為這項(xiàng)任務(wù)提供了一個自然的切入點(diǎn)蚓峦。然而滴劲，幾乎所有人類中樞神經(jīng)系統(tǒng)的基因表達(dá)研究都分析了由許多不同細(xì)胞類型組成的異質(zhì)性組織樣本底扳。
因此酿雪，通常認(rèn)為遏暴，這些樣本中基因表達(dá)的細(xì)胞起源無法確定，而這需要從物理上分離細(xì)胞類型指黎。雖然這種“自下而上”的方法很容易應(yīng)用于生物模型朋凉，但由于其體積小、可達(dá)性有限和抗解離性袋励，很難應(yīng)用于成人中樞神經(jīng)系統(tǒng)。
另一種方法是通過對大塊組織樣本進(jìn)行整合基因共表達(dá)分析來估計(jì)單個細(xì)胞類型的豐度與轉(zhuǎn)錄本之間的協(xié)變（covariation ）。這種“自上而下”的方法假設(shè)茬故，生物復(fù)制樣本中細(xì)胞成分的變化將推動在特定細(xì)胞類型中獨(dú)特或主要表達(dá)的轉(zhuǎn)錄本的共同變化盖灸。與單細(xì)胞方法相比，這種方法基于對數(shù)十億個細(xì)胞的聚合分析磺芭，因此可以對主要細(xì)胞類型的核心轉(zhuǎn)錄特征進(jìn)行高度可靠的推斷赁炎。
通過分析62個數(shù)據(jù)集的基因共表達(dá)關(guān)系，包括代表所有主要中樞神經(jīng)系統(tǒng)區(qū)域和技術(shù)平臺的bb0 7000神經(jīng)典型成人樣本钾腺，我們確定了星形膠質(zhì)細(xì)胞徙垫、少突膠質(zhì)細(xì)胞、小膠質(zhì)細(xì)胞和神經(jīng)元的一致轉(zhuǎn)錄特征放棒。我們創(chuàng)造了一個叫做“保真度”的新指標(biāo)姻报，它量化了基因表達(dá)水平與所有分析樣本中推斷的細(xì)胞類型豐度之間的關(guān)系。對細(xì)胞類型表達(dá)保真度最高的基因具有高敏感性和特異性：
Gene expression fidelity. A gene has high fidelity for a cell type if its expression is sensitive (it is consistently expressed by members of that cell type) and specific (it is not expressed by other cell types). Expression levels of high-fidelity genes are therefore highly correlated with the abundance of distinct cell types in heterogeneous tissue samples.
讓使用者透過以下兩種方法间螟，探討人類中樞神經(jīng)系統(tǒng)基因表達(dá)水平及細(xì)胞豐度的共變:
- CNS region / cell type search: The user can search by CNS region / cell type to retrieve the top 50 genes ranked by genome-wide expression fidelity.
- CNS region / gene search: The user can search by CNS region / gene to retrieve information about the associations of individual genes with major cell types, as well as top gene expression correlates.
目前支持21個廣泛的中樞神經(jīng)區(qū)域和4種主要的中樞神經(jīng)細(xì)胞類型(神經(jīng)元吴旋、星形膠質(zhì)細(xì)胞、少突膠質(zhì)細(xì)胞和小膠質(zhì)細(xì)胞)厢破。下面提供了帶注釋的使用示例荣瑟。有關(guān)更多詳情，請參閱本網(wǎng)站所附的刊物摩泪。
CNS region / cell type search
細(xì)胞類型搜索示例笆焰。人類中樞神經(jīng)系統(tǒng)星形膠質(zhì)細(xì)胞表達(dá)保真度排名前50位的基因(外軌)，以及這些基因的相關(guān)信息(內(nèi)軌)见坑。車輪圖（Wheel plots ）可下載為pdf格式嚷掠。根據(jù)特定CNS區(qū)域/細(xì)胞類型的表達(dá)保真度排序的完整基因列表，以及絕對表達(dá)水平鳄梅，可以從輪狀圖旁邊的鏈接下載為CSV文件叠国。數(shù)據(jù)下載頁面提供了所有CNS區(qū)域/單元格類型的完整表。
Expression fidelity (blue track) is a z-score that quantifies the extent to which the expression pattern of each gene was correlated with the inferred abundance of the cell type over all queried samples (in this example 7221 human CNS samples were included).
CNS expression (red track) is an average of the expression percentile ranks of each gene over all queried CNS regional datasets (in this example 62 datasets were included).
LoF intolerance (black track) is the probability that a given gene is intolerant to loss-of-function (LoF) mutations. Data are from the Exome Aggregation Consortium (ExAC).
PubMed citations (green track) is the number of citations in PubMed returned by queries for each gene symbol plus the name of the cell type (here, ‘a(chǎn)strocyte’).
PPI (interior lines) denote protein-protein interactions (PPI) from the STRING database.
提供查詢特定CNS區(qū)域/基因后返回的數(shù)據(jù)示例戴尸。在本例中粟焊，CNS區(qū)域?yàn)椤癆ll”，基因符號為“CNP”孙蒙。每個面板的含義解釋如下圖說明项棠。
更多詳細(xì)解釋參見：http://oldhamlab.ctec.ucsf.edu/about/
網(wǎng)站怎么用？
- 選擇一個腦區(qū)：
- 選擇一個細(xì)胞類型：
- 出結(jié)果導(dǎo)數(shù)據(jù)
