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DOSE-L1000-Viz:一款用于剂量反应转录组分析、以靶点为中心的探索和特征搜索的交互式Shiny应用程序。

DOSE-L1000-Viz: an interactive Shiny application for dose-response transcriptomic analysis, target-centric exploration, and signature search.

作者信息

Wang Junmin

机构信息

Data Sciences and Quantitative Biology, Discovery Sciences, Biopharmaceuticals R&D, AstraZeneca, Waltham, MA 02451, United States.

出版信息

Bioinformatics. 2025 Jul 1;41(7). doi: 10.1093/bioinformatics/btaf353.

DOI:10.1093/bioinformatics/btaf353
PMID:40608961
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC12237504/
Abstract

SUMMARY

Understanding how small molecules perturb gene expression is critical for guiding drug discovery. We present DOSE-L1000-Viz, a Shiny application that facilitates comprehensive exploration of compound-induced transcriptomic responses across doses, time points, and cell types. Powered by a dose-response database, DOSE-L1000-Viz features interactive visualization, target-centric compound ranking based on efficacy and potency, and a signature search module using reference gene sets derived from generalized additive models. We benchmarked signatures derived from generalized additive models against traditional methods and demonstrated the utility of DOSE-L1000-Viz through use cases in transcription factor modulation and drug repurposing.

AVAILABILITY AND IMPLEMENTATION

DOSE-L1000-Viz and the backend data are publicly accessible at: https://dosel1000.com. All code is publicly hosted on GitHub (https://github.com/JmWangBio/DOSEL1000Viz) and archived via Zenodo (https://doi.org/10.5281/zenodo.15532392).

摘要

摘要

了解小分子如何干扰基因表达对于指导药物发现至关重要。我们展示了DOSE-L1000-Viz,这是一个Shiny应用程序,有助于全面探索化合物在不同剂量、时间点和细胞类型下诱导的转录组反应。DOSE-L1000-Viz由剂量反应数据库提供支持,具有交互式可视化、基于疗效和效力的以靶点为中心的化合物排名,以及使用从广义相加模型派生的参考基因集的特征搜索模块。我们将从广义相加模型派生的特征与传统方法进行了基准测试,并通过转录因子调节和药物重新利用的用例展示了DOSE-L1000-Viz的实用性。

可用性和实现方式

DOSE-L1000-Viz和后端数据可在以下网址公开获取:https://dosel1000.com。所有代码都在GitHub(https://github.com/JmWangBio/DOSEL1000Viz)上公开托管,并通过Zenodo(https://doi.org/10.5281/zenodo.15532392)存档。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/12237504/6a8e7949e3b3/btaf353f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/12237504/6a8e7949e3b3/btaf353f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/503c/12237504/6a8e7949e3b3/btaf353f1.jpg

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本文引用的文献

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Nucleic Acids Res. 2025 Jul 7;53(W1):W338-W350. doi: 10.1093/nar/gkaf373.
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Drug target prediction through deep learning functional representation of gene signatures.通过基因特征的深度学习功能表示进行药物靶标预测。
Nat Commun. 2024 Feb 29;15(1):1853. doi: 10.1038/s41467-024-46089-y.
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DOSE-L1000: unveiling the intricate landscape of compound-induced transcriptional changes.DOSE-L1000:揭示化合物诱导的转录变化的复杂格局。
Bioinformatics. 2023 Nov 1;39(11). doi: 10.1093/bioinformatics/btad683.
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PAX8 as a Potential Target for Ovarian Cancer: What We Know so Far.PAX8作为卵巢癌的潜在靶点:目前我们所了解的情况。
Onco Targets Ther. 2022 Oct 21;15:1273-1280. doi: 10.2147/OTT.S361511. eCollection 2022.
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