A Chemical-Genetic Interaction Matrix Reveals Drug Mechanism and Genetic Architecture

This dataset is associated with an article bearing the same name ( https://doi.org/10.64898/2026.01.28.701823 ), describing the results of >400 CRISPR/Cas9 chemical-genetic genome-wide knockout screens covering 305 different compounds and 5 conditions. The dataset also contains meta-data about each compound as well as the raw and/or processed data necessary to reproduce various analyses and figures from the article. The contents of each table and sub-table (tab) are described in the overview tab of each file. Table contents are briefly described below. Table S1. Summary of the CGI dataset. (A) Sequenced samples. (B) Independent screens. (C) Compound details and verification. (D) NALM-6 gene expression. (E) CGIs detected. Table S2. CRANKS scores. Table S3. Known compound-target relationships. Table S4. Combined CRANKS scores for two independent TRAIL screens. Table S5. Jaccard similarity indices between screens in the CGI dataset. Pairs used in Fig. 2D are indicated by class. Table S6. Compound-transporter CGI scores. Table S7. (A) Compound dose-to-solubility ratios by screen. (B) Correlation coefficients of CRANKS scores with compound dose-to-solubility ratios. Table S8. Vemurafenib SSL hits and Gene Ontology annotations. Table S9. Predicted basic pKa and logP for compounds represented in the screen similarity network. Table S10. Mean genome-wide CRANKS score profile of the 28 screens in the phospholipidosis cluster. Table S11. LipidTOX Red assay determinations. (A) Cell counts and average LipidTOX levels. (B) Compound classification. Table S12. Average CRANKS scores for combined screens. (A) Nocodazole. (B) Active site mTOR inhibitors. (C) Rapamycin. (D) AICAR. (E) Pyridostatin and topoisomerase II inhibitors. (F) DHFR inhibitor screens. (G) PARP inhibitors. (H) CHEK1 inhibitors. Table S13. Comparison of CGIs for 9 shared compounds in this dataset and the Olivieri et al (2020) dataset. Table S14. Data for assessment of compound synergy/antagonism, including luminescence readings, treatments by well and log2 Bliss scores determined by compound pair. Table S15. (A) CRANKS2 scores. (B) Top 20,000 most correlated gene pairs. Table S16. RNA-seq data. (A) FK-506 versus DMSO and read counts by gene. (B) PPP3CA knockout versus wild-type controls. (C) PPP3R1 knockout versus wild-type controls. (D) Transcription rates in PABIR1 knockout clones. Table S17. List of DDR-associated genes. Table S18. (A) Significant exon-level CGIs. (B) Exon classification and validation data. Table S19. (A) Hypothetical gene CGIs with p-values <0.002 or absolute scores ≥2.5. (B) Hypothetical gene classification and mass spectral counts. Table S20. Correlation between gene CRANKS scores and population doublings.本数据集与一篇同名文章相关联（https://doi.org/10.64898/2026.01.28.701823），该文章报道了400余项CRISPR/Cas9介导的化学遗传全基因组敲除筛选实验结果，涵盖305种不同化合物与5种实验条件。本数据集同时包含每种化合物的元数据，以及复现该文章中各类分析与图表所需的原始和/或处理后数据。每个文件的概述标签（tab）中均对其包含的各表格及子表格内容进行了说明。下文将简要介绍各表格的核心内容。 表S1 本数据集的化合物-基因相互作用（Compound-Gene Interaction, CGI）摘要。(A) 测序样本；(B) 独立筛选实验；(C) 化合物详情与验证结果；(D) NALM-6细胞基因表达谱；(E) 检测到的CGI。 表S2 CRANKS评分。 表S3 已知的化合物-靶点相互作用关系。 表S4 两项独立的肿瘤坏死因子相关凋亡诱导配体（TNF-related apoptosis-inducing ligand, TRAIL）筛选的合并CRANKS评分。 表S5 本数据集内各筛选实验间的雅卡尔相似性指数。图2D中使用的样本对已按类别标注。 表S6 化合物-转运蛋白CGI评分。 表S7 (A) 各筛选实验的化合物剂量-溶解度比；(B) CRANKS评分与化合物剂量-溶解度比的相关系数。 表S8 维莫非尼（Vemurafenib）合成致死阳性结果与基因本体（Gene Ontology, GO）注释信息。 表S9 筛选相似性网络中所涉及化合物的理论碱性pKa与logP值。 表S10 磷脂沉积症聚类中28项筛选实验的全基因组CRANKS评分平均谱。 表S11 LipidTOX红色染色检测结果。(A) 细胞计数与平均LipidTOX水平；(B) 化合物分类。 表S12 合并筛选实验的平均CRANKS评分。(A) 诺考达唑；(B) mTOR活性位点抑制剂；(C) 雷帕霉素；(D) AICAR；(E) 吡啶司他汀与拓扑异构酶II抑制剂；(F) 二氢叶酸还原酶（Dihydrofolate Reductase, DHFR）抑制剂筛选实验；(G) 多聚ADP核糖聚合酶（Poly(ADP-ribose) polymerase, PARP）抑制剂；(H) 检查点激酶1（Checkpoint Kinase 1, CHEK1）抑制剂。 表S13 本数据集与Olivieri等人2020年发表的数据集中，共有的9种化合物对应的CGI对比。 表S14 化合物协同/拮抗作用评估数据，包括发光读数、孔板处理信息以及基于化合物对计算得到的log2 Bliss评分。 表S15 (A) CRANKS2评分；(B) 相关性排名前20000的基因对。 表S16 RNA测序数据。(A) 他克莫司（FK-506）与二甲基亚砜（Dimethyl sulfoxide, DMSO）处理组的基因读数计数；(B) PPP3CA基因敲除组与野生型对照组；(C) PPP3R1基因敲除组与野生型对照组；(D) PABIR1基因敲除克隆的转录速率。 表S17 DNA损伤响应（DNA Damage Response, DDR）相关基因列表。 表S18 (A) 外显子水平的显著CGI；(B) 外显子分类与验证数据。 表S19 (A) p值小于0.002或绝对评分≥2.5的假定基因CGI；(B) 假定基因分类与质谱计数。 表S20 基因CRANKS评分与群体倍增数的相关性。