ChromaFactor: deconvolution of single-molecule chromatin organization with non-negative matrix factorization.
ChromaFactor: deconvolution of single-molecule chromatin organization with non-negative matrix factorization.
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ChromaFactor：使用非负矩阵分解对单分子染色质组织进行反卷积。
DOI：
10.1101/2023.11.22.568268
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发表时间：
2023
期刊：
影响因子：
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通讯作者：
Pollard,KatherineS
中科院分区：
文献类型：
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作者：
Gunsalus,LauraM;Keiser,MichaelJ;Pollard,KatherineS
对单个细胞中染色质组织的研究为确定基因组结构和功能之间的因果关系提供了很大的希望。然而，单分子数据的分析受到极端但固有的异质性的阻碍，这使得确定单个染色质纤维对整体趋势的贡献具有挑战性。为了应对这一挑战，我们提出了一种基于非负矩阵分解的新型计算方法ChromaFactor，该方法将单分子染色质组织数据集去卷积为其最显著的主成分。色度因子能够识别数据集中最大方差的趋势，同时描述单个分子对每个组分的贡献。将我们的方法应用于不同基因组尺度上的两个单分子成像数据集，我们发现这些主要成分与关键功能表型显示出显著的相关性，包括激活转录、增强子-启动子距离和基因组间隔。此外，我们发现在单细胞水平上存在一些整体趋势，但只在一小部分细胞中存在，这表明基因组组织的关键变化可能是由特定的稀有亚群驱动的，而不是在所有细胞中均匀发生。染色质因子为理解单个DNA分子上染色质结构和功能之间的复杂相互作用提供了一个强大的工具，准确地确定了哪些亚群驱动了功能变化，并培养了对细胞异质性及其对整体基因组现象的影响的新见解。
The investigation of chromatin organization in single cells holds great promise for identifying causal relationships between genome structure and function. However, analysis of single-molecule data is hampered by extreme yet inherent heterogeneity, making it challenging to determine the contributions of individual chromatin fibers to bulk trends. To address this challenge, we propose ChromaFactor, a novel computational approach based on non-negative matrix factorization that deconvolves single-molecule chromatin organization datasets into their most salient primary components. ChromaFactor provides the ability to identify trends accounting for the maximum variance in the dataset while simultaneously describing the contribution of individual molecules to each component. Applying our approach to two single-molecule imaging datasets across different genomic scales, we find that these primary components demonstrate significant correlation with key functional phenotypes, including active transcription, enhancer-promoter distance, and genomic compartment. Also, we find that some bulk trends exist at the single-cell level, but only in a small fraction of cells, suggesting that critical changes in genome organization may be driven by specific rare subpopulations rather than occurring uniformly across all cells. ChromaFactor offers a robust tool for understanding the complex interplay between chromatin structure and function on individual DNA molecules, pinpointing which subpopulations drive functional changes and fostering new insights into cellular heterogeneity and its implications for bulk genomic phenomena.