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| Status |
Public on Apr 30, 2023 |
| Title |
A convolutional neural network STIFMap reveals associations between stromal stiffness and EMT in breast cancer |
| Organism |
Homo sapiens |
| Experiment type |
Expression profiling by high throughput sequencing
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| Summary |
Intratumor heterogeneity associates with poor patient outcome. Stromal stiffening also accompanies cancer. Whether cancers demonstrate stiffness heterogeneity, and if this is linked to tumor cell heterogeneity remains unclear. We developed a method to measure the stiffness heterogeneity in human breast tumors that quantifies the stromal stiffness each cell experiences and permits visual registration with biomarkers of tumor progression. We present Spatially Transformed Inferential Force Map (STIFMap) which exploits computer vision to precisely automate atomic force microscopy (AFM) indentation combined with a trained convolutional neural network to predict stromal elasticity with micron-resolution using collagen morphological features and ground truth AFM data. We registered high-elasticity regions within human breast tumors colocalizing with markers of mechanical activation and an epithelial-to-mesenchymal transition (EMT). The findings highlight the utility of STIFMaps to assess mechanical heterogeneity of human tumors across length scales from single cells to whole tissues and implicates stromal stiffness in tumor cell heterogeneity.
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| Overall design |
RNAseq of soft and stiff patient-derived xenograft tumors from three different patients. Each patient-stiffness combination has three replicates for 18 samples total.
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| Web link |
https://pubmed.ncbi.nlm.nih.gov/37322009/
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| Contributor(s) |
Northey J, Stashko C, Weaver V |
| Citation(s) |
37322009 |
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| Submission date |
Jul 13, 2021 |
| Last update date |
Aug 02, 2023 |
| Contact name |
Valerie M Weaver |
| Organization name |
UCSF
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| Department |
Surgery
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| Lab |
Weaver Lab
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| Street address |
513 Parnassus Avenue, HSE 560
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| City |
San Francisco |
| State/province |
CA |
| ZIP/Postal code |
94143 |
| Country |
USA |
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| Platforms (1) |
| GPL24676 |
Illumina NovaSeq 6000 (Homo sapiens) |
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| Samples (18)
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| GSM5444448 |
Breast tumor 1, soft gel, rep1 [B63703] |
| GSM5444449 |
Breast tumor 1, soft gel, rep2 [B63704] |
| GSM5444450 |
Breast tumor 1, soft gel, rep3 [B63705] |
| GSM5444451 |
Breast tumor 1, stiff gel, rep1 [B63801] |
| GSM5444452 |
Breast tumor 1, stiff gel, rep2 [B63802] |
| GSM5444453 |
Breast tumor 1, stiff gel, rep3 [B63803] |
| GSM5444454 |
Breast tumor 2, soft gel, rep1 [H12701] |
| GSM5444455 |
Breast tumor 2, soft gel, rep2 [H12702] |
| GSM5444456 |
Breast tumor 2, soft gel, rep3 [H12703] |
| GSM5444457 |
Breast tumor 2, stiff gel, rep1 [H12802] |
| GSM5444458 |
Breast tumor 2, stiff gel, rep2 [H12804] |
| GSM5444459 |
Breast tumor 2, stiff gel, rep3 [H12805] |
| GSM5444460 |
Breast tumor 3, soft gel, rep1 [B43202] |
| GSM5444461 |
Breast tumor 3, soft gel, rep2 [B43203] |
| GSM5444462 |
Breast tumor 3, soft gel, rep3 [B43204] |
| GSM5444463 |
Breast tumor 3, stiff gel, rep1 [B43104] |
| GSM5444464 |
Breast tumor 3, stiff gel, rep2 [B43303] |
| GSM5444465 |
Breast tumor 3, stiff gel, rep3 [B43304] |
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| Relations |
| BioProject |
PRJNA746133 |
| SRA |
SRP328119 |
| Supplementary file |
Size |
Download |
File type/resource |
| GSE179983_GO_MSigDB_allpdx_human_greater_in_soft.txt.gz |
706.4 Kb |
(ftp)(http) |
TXT |
| GSE179983_GO_MSigDB_allpdx_human_greater_in_stiff.txt.gz |
714.8 Kb |
(ftp)(http) |
TXT |
| GSE179983_pdx_hs33_counts.txt.gz |
1.1 Mb |
(ftp)(http) |
TXT |
SRA Run Selector |
| Raw data are available in SRA |
| Processed data are available on Series record |
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