Figure - PMC

Skip to main content

An official website of the United States government

Here's how you know

Here's how you know

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Secure .gov websites use HTTPS
A lock ( ) or https:// means you've safely connected to the .gov website. Share sensitive information only on official, secure websites.

View full-text article in PMC

. 2024 May 29;56(7):1482–1493. doi: 10.1038/s41588-024-01758-y

Search in PMC
Search in PubMed
View in NLM Catalog
Add to search

© The Author(s) 2024

Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.

PMC Copyright notice

Extended Data Fig. 1 — a, Table of genes shown in Fig. 1b. b, c, d, Heatmaps of rxrx3 (above diagonal) and cpg0016 (below diagonal) data for selected biological pathways with corresponding pathway diagrams for JAK/STAT, TGF-beta, and insulin biology. Data not present in cpg0016 shown in gray. b, Example interleukin (IL) 6 pathway: IL6, IL6R, IL6ST, JAK1, and STAT3 activate the IL-6 signaling pathway⁷⁶. CRISPR-Cas9 targeting of these genes leads to similar cellular phenotypes and produces positive cosine similarities (red squares between IL6, IL6R, IL6ST, JAK1, and STAT3 in the heatmap). As inhibitors of the IL-6 pathway, SOCS3 and PTPN2 demonstrate a negative cosine similarity to the pathway components IL6/IL6R/IL6ST/JAK1/STAT3, especially in the rxrx3 HUVEC data (blue squares)^76,77. c, Example TGF-beta pathway: FURIN, TGFB1, TGFBR1, TGFBR2, SMAD2, and SMAD3 activate the TGF-beta pathway. CRISPR-Cas9 targeting of these genes gives a similar cellular phenotype and high cosine similarity (red squares in the heatmap)⁷⁸. SMURF2 and SKI inhibit the TGF-beta pathway, and CRISPR-Cas9 targeting of SMURF2 and SKI, show high cosine similarity to each other but negative cosine values to FURIN, TGFB1, TGFBR1, TGFBR2, SMAD2, and SMAD3 (blue squares)^78,79. Grey squares indicate genes not present in the cpg0016 data. d, Example insulin pathway: INSR, IRS2, AKT1, PIK3CA transmit insulin signaling⁸⁰. CRISPR-Cas9 targeting these factors gives similar phenotypes and therefore they are highly cosine-similar (red squares between INSR/IRS2/AKT1/PIK3CA in the heatmap). GRB10 and FOXO1 inhibit insulin signaling, reflected in negative cosine similarities between CRISPR-Cas9 targeting of GRB10 and INSR, IRS2, AKT1 and PIK3CA (blue squares)⁸⁰. Grey squares indicate genes not present in the cpg0016 data.