Transcriptome profiling followed by differential gene expression analysis often leads to lists of genes that are hard to analyze and interpret. Functional genomics tools are powerful approaches for downstream analysis, as they summarize the large and noisy gene expression space into a smaller number of biological meaningful features. In particular, methods that estimate the activity of processes by mapping transcripts level to process members are popular. However, footprints of either a pathway or transcription factor (TF) on gene expression show superior performance over mapping-based gene sets. These footprints are largely developed for humans and their usability in the broadly-used model organism Mus musculus is uncertain. Evolutionary conservation of the gene regulatory system suggests that footprints of human pathways and TFs can functionally characterize mice data. In this paper we analyze this hypothesis. We perform a comprehensive benchmark study exploiting two state-of-the-art footprint methods, DoRothEA and an extended version of PROGENy. These methods infer TF and pathway activity, respectively. Our results show that both can recover mouse perturbations, confirming our hypothesis that footprints are conserved between mice and humans. Subsequently, we illustrate the usability of PROGENy and DoRothEA by recovering pathway/TF-disease associations from newly generated disease sets. Additionally, we provide pathway and TF activity scores for a large collection of human and mouse perturbation and disease experiments (2374). We believe that this resource, available for interactive exploration and download (https://saezlab.shinyapps.io/footprint_scores/), can have broad applications including the study of diseases and therapeutics.

中文翻译：

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将监管知识从人转移到小鼠，以进行功能基因组分析。

转录组分析以及随后的差异基因表达分析通常会导致难以分析和解释的基因列表。功能基因组学工具是用于下游分析的强大方法，因为它们将大而嘈杂的基因表达空间概括为少量的生物学有意义的特征。特别地，通过将​​转录物水平映射到过程成员来估计过程活动的方法是流行的。但是，基因表达的途径或转录因子（TF）的足迹显示出优于基于图谱的基因集的性能。这些足迹主要是为人类开发的，它们在广泛使用的模型生物小家鼠中的可用性尚不确定。基因调节系统的进化保守性表明，人类途径和TF的足迹可以在功能上表征小鼠数据。在本文中，我们分析了这一假设。我们利用两种最先进的封装方法DoRothEA和PROGENy的扩展版进行了全面的基准研究。这些方法分别推断出TF和途径活性。我们的结果表明，两者都可以恢复小鼠的摄动，这证实了我们的假设，即人与鼠之间的脚印是保守的。随后，我们通过从新生成的疾病集中恢复途径/ TF-疾病关联来说明PROGENy和DoRothEA的可用性。此外，我们提供了大量人类和小鼠摄动和疾病实验的通路和TF活性评分（2374）。我们认为，这种资源