PhyloVelo enhances transcriptomic velocity field mapping using monotonically expressed genes.
PhyloVelo enhances transcriptomic velocity field mapping using monotonically expressed genes.
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DOI：
10.1038/s41587-023-01887-5
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发表时间：
2023-07
影响因子：
46.9
通讯作者：
Kun Wang;Liangzhen Hou;Xin Wang;Xiangwei Zhai;Zhaolian Lu;Zhike Zi;Weiwei Zhai;Xionglei He;C. Curtis;Danya Zhou;Zheng Hu
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文献类型：
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作者：
Kun Wang;Liangzhen Hou;Xin Wang;Xiangwei Zhai;Zhaolian Lu;Zhike Zi;Weiwei Zhai;Xionglei He;C. Curtis;Danya Zhou;Zheng Hu
单细胞RNA测序（scRNA-seq）是研究细胞分化的有力方法，但准确跟踪细胞命运转变可能具有挑战性，尤其是在疾病条件下。在这里，我们介绍PhyloVelo，一个计算框架，估计速度的转录组动态使用单调表达的基因（MEGs）或基因的表达模式，增加或减少，但不循环，通过系统发育时间。通过整合scRNA-seq数据与谱系信息，PhyloVelo识别MEG并重建转录组速度场。我们使用模拟数据和秀丽隐杆线虫地面真实数据验证了PhyloVelo，成功地恢复了线性，分叉和收敛微分。将PhyloVelo应用于使用CRISPR-Cas9编辑、慢病毒条形码或免疫组谱分析生成的七个谱系追踪scRNA-seq数据集，证明了其在推断复杂谱系轨迹方面的高准确性和鲁棒性，同时优于RNA速度。此外，我们发现，MEG跨组织和生物体在翻译和核糖体生物合成中具有相似的功能。
Single-cell RNA sequencing (scRNA-seq) is a powerful approach for studying cellular differentiation, but accurately tracking cell fate transitions can be challenging, especially in disease conditions. Here we introduce PhyloVelo, a computational framework that estimates the velocity of transcriptomic dynamics by using monotonically expressed genes (MEGs) or genes with expression patterns that either increase or decrease, but do not cycle, through phylogenetic time. Through integration of scRNA-seq data with lineage information, PhyloVelo identifies MEGs and reconstructs a transcriptomic velocity field. We validate PhyloVelo using simulated data andCaenorhabditis elegansground truth data, successfully recovering linear, bifurcated and convergent differentiations. Applying PhyloVelo to seven lineage-traced scRNA-seq datasets, generated using CRISPR–Cas9 editing, lentiviral barcoding or immune repertoire profiling, demonstrates its high accuracy and robustness in inferring complex lineage trajectories while outperforming RNA velocity. Additionally, we discovered that MEGs across tissues and organisms share similar functions in translation and ribosome biogenesis.