Learning to predict RNA sequence expressions from whole slide images with applications for search and classification
Open accessAbstract
Deep learning methods are widely applied in digital pathology to address clinical challenges such as prognosis and diagnosis. As one of the most recent applications, deep models have also been used to extract molecular features from whole slide images. Although molecular tests carry rich information, they are often expensive, time-consuming, and require additional tissue to sample. In this paper, we propose tRNAsformer, an attention-based topology that can learn both to predict the bulk RNA-seq from an image and represent the whole slide image of a glass slide simultaneously. The tRNAsformer uses multiple instance learning to solve a weakly supervised problem while the pixel-level annotation is not available for an image. We conducted several experiments and achieved better performance and faster convergence in comparison to the state-of-the-art algorithms. The proposed tRNAsformer can assist as a computational pathology tool to facilitate a new generation of search and classification methods by combining the tissue morphology and the molecular fingerprint of the biopsy samples.
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Some deep learning approaches have focused on detecting molecular alterations in image data, while most existing studies have centered on inferring spatial transcriptome or bulk transcriptome information from histopathology images.
“While some deep learning approaches have focused on detecting molecular alterations in image data [132], most existing studies have centered on inferring spatial transcriptome or bulk transcriptome information from histopathology images [133–136].”
From Challenges in AI-driven Biomedical Multimodal Data Fusion and Analysis (2025) · cites this paper as [136]
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References 31 · Cited by 40
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- [1]Hou, L. et al. Patch-based convolutional neural network for whole slide tissue image classification. in Proceedings of the IEEE Conference on Computervision and Pattern Recognition 2424–2433 (2016). PMC5085270 27795661
- [2]Kalra S Pan-cancer diagnostic consensus through searching archival histopathology images using artificial intelligence NPJ Digit. Med. 2020 3 1 15 10.1038/s41746-020-0238-2 32195366 PMC7064517 · DOI
- [3]Wang H Mitosis detection in breast cancer pathology images by combining handcrafted and convolutional neural network features J. Med. Imaging 2014 1 034003 10.1117/1.JMI.1.3.034003 PMC4479031 26158062 · DOI
- [5]Schmauch B A deep learning model to predict rna-seq expression of tumours from whole slide images Nat. Commun. 2020 11 1 15 10.1038/s41467-020-17678-4 32747659 PMC7400514 · DOI · Paper page
- [6]Levy-Jurgenson A Tekpli X Kristensen VN Yakhini Z Spatial transcriptomics inferred from pathology whole-slide images links tumor heterogeneity to survival in breast and lung cancer Sci. Rep. 2020 10 1 11 10.1038/s41598-020-75708-z 33139755 PMC7606448 · DOI · Paper page
- [7]He B Integrating spatial gene expression and breast tumour morphology via deep learning Nat. Biomed. Eng. 2020 4 827 834 10.1038/s41551-020-0578-x 32572199 · DOI · Paper page
- [8]Tavolara TE Deep learning predicts gene expression as an intermediate data modality to identify susceptibility patterns in mycobacterium tuberculosis infected diversity outbred mice EBioMedicine 2021 67 103388 10.1016/j.ebiom.2021.103388 34000621 PMC8138606 · DOI
- [9]Coudray N Classification and mutation prediction from non-small cell lung cancer histopathology images using deep learning Nat. Med. 2018 24 1559 1567 10.1038/s41591-018-0177-5 30224757 PMC9847512 · DOI · Paper page
- [10]Schaumberg, A. J., Rubin, M. A. & Fuchs, T. J. H&E-stained whole slide image deep learning predicts spop mutation state in prostate cancer. Preprint at BioRxiv10.1101/064279 (2017).
- [11]Segal E Friedman N Kaminski N Regev A Koller D From signatures to models: understanding cancer using microarrays Nat. Genet. 2005 37 S38 S45 10.1038/ng1561 15920529 · DOI
- [12]Kamps R Next-generation sequencing in oncology: genetic diagnosis, risk prediction and cancer classification Int. J. Mol. Sci. 2017 18 308 10.3390/ijms18020308 28146134 PMC5343844 · DOI
- [13]Sung H Global cancer statistics 2020: Globocan estimates of incidence and mortality worldwide for 36 cancers in 185 countries CA: Cancer J. Clin. 2021 71 209 249 33538338
- [14]Shuch B Understanding pathologic variants of renal cell carcinoma: distilling therapeutic opportunities from biologic complexity Eur. Urol. 2015 67 85 97 10.1016/j.eururo.2014.04.029 24857407 · DOI
- [15]Tabibu S Vinod P Jawahar C Pan-renal cell carcinoma classification and survival prediction from histopathology images using deep learning Sci. Rep. 2019 9 10509 10.1038/s41598-019-46718-3 31324828 PMC6642160 · DOI
- [16]Dietterich TG Lathrop RH Lozano-Pérez T Solving the multiple instance problem with axis-parallel rectangles Artif. Intell. 1997 89 31 71 10.1016/S0004-3702(96)00034-3 · DOI · Paper page
- [17]Hubbard T The ensembl genome database project Nucleic Acids Res. 2002 30 38 41 10.1093/nar/30.1.38 11752248 PMC99161 · DOI
- [18]Bartha Á Győrffy B Tnmplot. com: a web tool for the comparison of gene expression in normal, tumor and metastatic tissues Int. J. Mol. Sci. 2021 22 2622 10.3390/ijms22052622 33807717 PMC7961455 · DOI
- [19]Luo M-S Huang G-J Liu B-X Immune infiltration in nasopharyngeal carcinoma based on gene expression Medicine 2019 98 e17311 10.1097/MD.0000000000017311 31574860 PMC6775332 · DOI
- [20]Hoffman GE Schadt E E. variancepartition: interpreting drivers of variation in complex gene expression studies BMC Bioinforma. 2016 17 1 13 10.1186/s12859-016-1323-z PMC5123296 27884101 · DOI · Paper page
- [21]Campbell-Staton SC Velotta JP Winchell KM Selection on adaptive and maladaptive gene expression plasticity during thermal adaptation to urban heat islands Nat. Commun. 2021 12 1 14 10.1038/s41467-021-26334-4 34702827 PMC8548502 · DOI
- [22]Avsec Ž Effective gene expression prediction from sequence by integrating long-range interactions Nat. Methods 2021 18 1196 1203 10.1038/s41592-021-01252-x 34608324 PMC8490152 · DOI · Paper page
- [25]Spyromitros-Xioufis E Tsoumakas G Groves W Vlahavas I Multi-target regression via input space expansion: treating targets as inputs Mach. Learn. 2016 104 55 98 10.1007/s10994-016-5546-z · DOI
- [26]Stacke, K., Eilertsen, G., Unger, J. & Lundström, C. A closer look at domain shift for deep learning in histopathology. Preprint at https://arxiv.org/abs/1909.11575 (2019). 33085623 · arXiv
- [27]Asilian Bidgoli A Rahnamayan S Dehkharghanian T Grami A Tizhoosh H Bias reduction in representation of histopathology images using deep feature selection Sci. Rep. 2022 12 1 12 10.1038/s41598-022-24317-z 36411301 PMC9678861 · DOI
- [28]Dehkharghanian, T. et al. Biased data, biased AI: deep networks predict the acquisition site of TCGA images. BMC Diagnostic Pathology (2023). PMC10189924 37198691
- [29]Safarpoor, A., Shafiei, S., Gonzalez, R., Parwani, A. & Tizhoosh, H. Renal cell carcinoma whole-slide image classification and search using deep learning. Research Square10.21203/rs.3.rs-971708/v1 (2021).
- [31]Dehghani, M., Zamani, H., Severyn, A., Kamps, J. & Croft, W. B. Neural ranking models with weak supervision. in Proceedings of the 40th International ACM SIGIR Conference on Research and Development in Information Retrieval 65–74 (2017).
- [32]Sikaroudi, M. et al. Supervision and source domain impact on representation learning: a histopathology case study. in 2020 42nd Annual International Conference of the IEEE Engineering in Medicine & Biology Society (EMBC) 1400–1403 (IEEE, 2020). 33018251
- [33]Gildenblat, J. & Klaiman, E. Self-supervised similarity learning for digital pathology. Preprint at https://arxiv.org/abs/1905.08139 (2019). · arXiv
- [34]Dosovitskiy, A. et al. An image is worth 16 × 16 words: Transformers for image recognition at scale. Preprint at https://arxiv.org/abs/2010.11929 (2020). · arXiv
- [35]Hendrycks, D. & Gimpel, K. Gaussian error linear units (gelus). Preprint at https://arxiv.org/abs/1606.08415 (2016). · arXiv
- [36]Loshchilov, I. & Hutter, F. Decoupled weight decay regularization. Preprint at https://arxiv.org/abs/1711.05101 (2017). · arXiv
- Authors
- Alsaafin, A., Safarpoor, A., Sikaroudi, M., Hipp, J. D., & Tizhoosh, H. R.
- Affiliations
- Mayo Clinic (US)
- University of Waterloo (CA)
- Corresponding author
- Tizhoosh, H. R.
- Venue
- Communications Biology
- Published
- 2023-03-22
- Volume
- 6
- Issue
- 1
- Pages
- 304-304
- ISSN
- 2399-3642 (ISSN-L)
- PMC
- PMC10033650
- OpenAlex
- W4353065773
- Cited by
- 40
- References
- 31
- Citations by year
- 2026: 6 · 2025: 14 · 2024: 11 · 2023: 8 · 2022: 1
- FWCI
- 3.68
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- Communications Biology (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- Government of Ontario
- Topics
- Physical Sciences › Computer Science › Artificial Intelligence › AI in cancer detection
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Single-cell and spatial transcriptomics
- Health Sciences › Medicine › Radiology, Nuclear Medicine and Imaging › Radiomics and Machine Learning in Medical Imaging
- Keywords
- whole slide images, multiple instance learning, weakly supervised learning, digital pathology, computational pathology, tissue morphology, molecular fingerprints, image representation, image search
- MeSH terms
- RNA-Seq, Algorithms, Base Sequence
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