Screening single-cell trajectories via continuity assessments for cell transition potential.
Screening single-cell trajectories via continuity assessments for cell transition potential.
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DOI：
10.1093/bib/bbad356
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发表时间：
2023-09-22
影响因子：
9.5
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中科院分区：
文献类型：
--
作者：
单细胞测序和数据分析的进展使得基于转录组变异来推断跨越异质细胞群体的生物学轨迹成为可能。这些轨迹产生了丰富的新的见解动态过程，如发展和分化。然而，轨迹分析依赖于轨迹连续性的假设，并且实验限制排除了满足此条件的一些真实世界场景。目前缺乏评估指标使得难以确定给定轨迹是否/何时偏离连续性，并且这种偏离对推断准确性的影响尚不清楚。通过分析引入到计算机和真实的单细胞数据中的模拟中断，我们发现不连续性导致轨迹推断的准确性急剧下降。然后，我们生成了一个简单的评分算法来评估轨迹的连续性，并发现在肠道干细胞发育和CD 8 + T细胞分化的真实案例中的连续性评估有效地识别了与经验知识一致的轨迹。这种评估方法也可以用于缺乏先验知识的情况下，以筛选推断谱系的池，以确定其是否符合假定的连续性，并作为一种手段，通过实证研究来权衡更高的可能性轨迹，以进行验证，如我们在银屑病关节炎和急性肾损伤中的案例研究所示。这个工具可以通过github在qingshanni/scEGRET免费获得。
Advances in single-cell sequencing and data analysis have made it possible to infer biological trajectories spanning heterogeneous cell populations based on transcriptome variation. These trajectories yield a wealth of novel insights into dynamic processes such as development and differentiation. However, trajectory analysis relies on an assumption of trajectory continuity, and experimental limitations preclude some real-world scenarios from meeting this condition. The current lack of assessment metrics makes it difficult to ascertain if/when a given trajectory deviates from continuity, and what impact such a divergence would have on inference accuracy is unclear. By analyzing simulated breaks introduced into in silico and real single-cell data, we found that discontinuity caused precipitous drops in the accuracy of trajectory inference. We then generate a simple scoring algorithm for assessing trajectory continuity, and found that continuity assessments in real-world cases of intestinal stem cell development and CD8 + T cells differentiation efficiently identifies trajectories consistent with empirical knowledge. This assessment approach can also be used in cases where a priori knowledge is lacking to screen a pool of inferred lineages for their adherence to presumed continuity, and serve as a means for weighing higher likelihood trajectories for validation via empirical studies, as exemplified by our case studies in psoriatic arthritis and acute kidney injury. This tool is freely available through github at qingshanni/scEGRET.
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影响因子：
14.9
作者：
Gillespie M;Jassal B;Stephan R;Milacic M;Rothfels K;Senff-Ribeiro A;Griss J;Sevilla C;Matthews L;Gong C;Deng C;Varusai T;Ragueneau E;Haider Y;May B;Shamovsky V;Weiser J;Brunson T;Sanati N;Beckman L;Shao X;Fabregat A;Sidiropoulos K;Murillo J;Viteri G;Cook J;Shorser S;Bader G;Demir E;Sander C;Haw R;Wu G;Stein L;Hermjakob H;D'Eustachio P
通讯作者：
D'Eustachio P
影响因子：
12.3
作者：
通讯作者：
--
影响因子：
14.9
作者：
Ji Z;Ji H
通讯作者：
Ji H
影响因子：
12.3
作者：
Jiang R;Sun T;Song D;Li JJ
通讯作者：
Li JJ
影响因子：
5.8
作者：
Alquicira-Hernandez J;Powell JE;Phan TG
通讯作者：
Phan TG