IP Library Granted Patent US 12,586,391
Granted Patent B2
US 12,586,391 · App. 18/511,998 · Granted Mar 24, 2026

Systems and methods for deconvolving cell types in histology slide images, using super-resolution spatial transcriptomics data

Inventors: Chi-Sing Ho (Redwood City, CA); Tianyou Luo (Chapel Hill, NC); Ameen Salahudeen (Oak Park, IL); Luca Lonini (Chicago, IL)
Assignee: TEMPUS AI, INC.
G06V20/698G06T3/40G06T7/0012G06T7/10G06T7/149G06V10/46G06V10/82G06V20/695G16H30/40G06T2207/10056G06T2207/20081G06T2207/20132G06T2207/30024
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Quick Facts
Patent No.
US 12,586,391
App. No.
18/511,998
Granted
Mar 24, 2026
Kind
B2
Abstract

A computer-implemented method, computing system and computer-readable medium include receiving training data and training a machine learning model to generate a cell expression map. A computer-implemented method, computing system and computer-readable medium includes receiving a histology image and a cell segmentation map and processing them using a trained machine learning model.

Claims (56)

1 . A computer-implemented method for training a machine learning model to classify cells in a histology image, the method comprising:

receiving, via one or more processors, training data; and

training a machine learning model, using the training data, to generate a cell expression map corresponding to a cropped portion of a super-resolved gene expression heat map,

wherein the cell expression map includes a plurality of cell contours, each including respective aggregated gene expression values.

2 . The computer-implemented method of claim 1 , wherein the training data includes at least one of (i) one or more cell segmentation maps, (ii) one or more spatial transcriptomics data sets, and (iii) one or more pathologists' annotations.

3 . The computer-implemented method of claim 2 , wherein at least one of the cell segmentation maps corresponds to a respective one of the spatial transcriptomics data sets and to a respective one of the pathologists' annotations.

4 . The computer-implemented method of claim 1 , further comprising:

generating an image mask corresponding to the training data; and

providing the image mask to the machine learning model with the training data, to enable the model to output features enabling model outputs to be matched to model inputs.

5 . The computer-implemented method of claim 1 , further comprising:

training the machine learning model to determine the cropped portion of the super-resolved gene expression heat map by linking coordinates of the super-resolved gene expression heat map to coordinates of images in the training data.

6 . A computer-implemented method for classifying cells in an histology image, the method comprising:

receiving, via one or more processors, the histology image and a cell segmentation map;

processing the histology image and the cell segmentation map using a trained machine learning model to generate a cell expression map including a plurality of cell contours, each including a respective predicted aggregated gene expression,

wherein the machine learning model is trained using training data; and

for each of the cell contours, processing the cell contour to generate a respective predicted cell type using a model trained to predict cell types based on aggregated gene expression information.

7 . The computer-implemented method of claim 6 , wherein the aggregated gene expression information includes an abundance value or expression level for each gene in a plurality of genes.

8 . The computer-implemented method of claim 6 , wherein processing the cell contour to generate the respective cell type includes generating a gene-by-gene comatrix, wherein one dimension of the comatrix represents one individual cell and another dimension represents an expression value for a particular gene for a particular cell.

9 . The computer-implemented method of claim 6 , further comprising:

processing each cell contour's gene expression profile using a trained cell type prediction machine learning model to determine a type of the cell.

10 . The computer-implemented method of claim 9 , wherein the trained cell type prediction machine learning model is a logistic regression machine learning model.

11 . A computing system for training a machine learning model to classify cells in a histology image, comprising:

one or more processors; and

one or more memories having stored thereon computer-executable instructions that, when executed by the one or more processors, cause the computing system to:

receive, via one or more processors, training data; and

train a machine learning model, using the training data, to generate a cell expression map corresponding to a cropped portion of a super-resolved gene expression heat map,

wherein the cell expression map includes a plurality of cell contours, each including respective aggregated gene expression values.

12 . The computing system of claim 11 , wherein the training data includes at least one of (i) one or more cell segmentation maps, (ii) one or more spatial transcriptomics data sets, and (iii) one or more pathologists' annotations.

13 . The computing system of claim 12 , wherein at least one of the cell segmentation maps corresponds to a respective one of the spatial transcriptomics data sets and to a respective one of the pathologists' annotations.

14 . The computing system of claim 11 , the instructions having stored thereon further instructions that, when executed by the one or more processors, cause the computing system to:

generate an image mask corresponding to the training data; and

provide the image mask to the machine learning model with the training data, to enable the model to output features enabling the model output to be matched to model inputs.

15 . The computing system of claim 11 , the instructions having stored thereon further instructions that, when executed by the one or more processors, cause the computing system to:

train the machine learning model to determine the cropped portion of the super-resolved gene expression heat map by linking coordinates of the super-resolved gene expression map to coordinates of images in the training data.

16 . A computing system for training a machine learning model to classify cells in a histology image, comprising:

one or more processors; and

one or more memories having stored thereon computer-executable instructions that, when executed by the one or more processors, cause the computing system to:

receive, via one or more processors, the histology image and a cell segmentation map;

process the histology image and the cell segmentation map using a trained machine learning model to generate a cell expression map including a plurality of cell contours, each including a respective predicted aggregated gene expression,

wherein the machine learning model is trained using training data; and

for each of the cell contours, process the cell contour to generate a respective predicted cell type using a model trained to predict cell types based on aggregated gene expression information.

17 . The computing system of claim 16 , wherein the aggregated gene expression information includes an abundance value or expression level for each gene in a plurality of genes.

18 . The computing system of claim 16 , the instructions having stored thereon further instructions that, when executed by the one or more processors, cause the computing system to:

generate a gene-by-gene comatrix, wherein one dimension of the comatrix represents one individual cell and another dimension represents an expression value for a particular gene for a particular cell.

19 . The computing system of claim 16 , the instructions having stored thereon further instructions that, when executed by the one or more processors, cause the computing system to:

process each cell contour's gene expression profile using a trained cell type prediction machine learning model to determine a type of the cell.

20 . The computing system of claim 19 , wherein the trained cell type prediction machine learning model is a logistic regression machine learning model.

21 . A non-transitory computer-readable medium having stored thereon computer-executable instructions that, when executed by one or more processors, cause a computer to:

receive, via one or more processors, training data; and

train a machine learning model, using the training data, to generate a cell expression map corresponding to a cropped portion of a super-resolved gene expression heat map,

wherein the cell expression map includes a plurality of cell contours, each including respective aggregated gene expression values.

22 . A non-transitory computer-readable medium having stored thereon computer-executable instructions that, when executed by one or more processors, cause a computer to:

receive, via one or more processors, a histology image and a cell segmentation map;

process the histology image and the cell segmentation map using a trained machine learning model to generate a cell expression map including a plurality of cell contours, each including a respective predicted aggregated gene expression,

wherein the machine learning model is trained using training data; and

for each of the cell contours, process the cell contour to generate a respective predicted cell type using a model trained to predict cell types based on aggregated gene expression information.

Assignments (4)
RELEASE OF SECURITY INTEREST Recorded May 14, 2026
From: ARES CAPITAL CORPORATION, AS COLLATERAL AGENT
To: TEMPUS AI, INC. (F/K/A TEMPUS LABS, INC.)
Reel/Frame 075577/0513 →
SECURITY INTEREST Recorded Jun 2, 2025
From: TEMPUS AI, INC.
To: ARES CAPITAL CORPORATION, AS COLLATERAL AGENT
Reel/Frame 071468/0107 →
ASSIGNMENT OF ASSIGNOR'S INTEREST Recorded Jan 17, 2025
From: HO, CHI-SING; LUO, TIANYOU; SALAHUDEEN, AMEEN; LONINI, LUCA
To: TEMPUS AI, INC.
Reel/Frame 069918/0898 →
CHANGE OF NAME Recorded Feb 9, 2024
From: TEMPUS LABS, INC.
To: TEMPUS AI, INC.
Reel/Frame 066544/0110 →
Continuity (2)
Provisional Application 63426009 · Nov 16, 2022
Related Publication 20240161519A1 · May 16, 2024
References Cited (20)
US 10957041B2 · Yip et al. · 2021 [cited by applicant]
US 10991097B2 · Yip et al. · 2021 [cited by applicant]
US 11348239B2 · Yip et al. · 2022 [cited by applicant]
US 20240266002A1 · Adeleke · 2024 [cited by examiner]
US 20250014681A1 · Zhang · 2025 [cited by examiner]
US 20250218534A1 · Jaganathan · 2025 [cited by examiner]
Zhao et al. “Innovative super-resolution in spatial transcriptomics: a transformer model exploiting histology images and spatial gene expression.” Briefings in Bioinformatics, 25(2), pp. 1-15 (Year: 2024). [cited by examiner]
Biancalani et al. “Deep learning and alignment of spatially resolved single-cell transcriptomes with Tangram.” Nature methods, 18(11), pp. 1352-1362 (Year: 2021). [cited by examiner]
Duan, et al. “Spatially resolved transcriptomics: advances and applications.” Blood Science, 5(1), pp. 1-14 (Year: 2023). [cited by examiner]
Fang et al. “Computational approaches and challenges in spatial transcriptomics.” Genomics, proteomics & bioinformatics, 21(1), pp. 24-47 (Year: 2023). [cited by examiner]
Li et al. “Emerging artificial intelligence applications in spatial transcriptomics analysis.” Computational and Structural Biotechnology Journal, 20, pp. 2895-2908 (Year: 2022). [cited by examiner]
Liu et al. “Analysis and visualization of spatial transcriptomic data.” Frontiers in genetics, 12, p. 785290 (Year: 2022). [cited by examiner]
Murchan et al. “Deep learning of histopathological features for the prediction of tumor molecular genetics.” Diagnostics, 11(8), p. 1406 (Year: 2021). [cited by examiner]
Pang et al. “Leveraging information in spatial transcriptomics to predict super-resolution gene expression from histology images in tumors.” BioRxiv, pp. 2021-11 (Year: 2021). [cited by examiner]
Zeng et al. “Statistical and machine learning methods for spatially resolved transcriptomics data analysis.” Genome biology, 23(1), p. 83 (Year: 2022). [cited by examiner]
Aran et al., Reference-based analysis of lung single-cell sequencing reveals a transitional profibrotic macrophage, Nat. Immunol., 20(2): 163-172 (Feb. 2019). [cited by applicant]
Aran et al., xCell: digitally portraying the tissue cellular heterogeneity landscape, Genome Biology, 18: 220 (2017). [cited by applicant]
Bergenstrahle et al. Super-resolved spatial transcriptomics by deep data fusion, Nat Biotechnol., 40(4):476-479 (Apr. 2022). [cited by applicant]
Beaubier et al., Integrated genomic profiling expands clinical options for patients with cancer, Nat Biotechnol. 37(11): 1351-1360 (Nov. 2019). [cited by applicant]
Goltsev et al., Deep Profiling of Mouse Splenic Architecture with CODEX Multiplexed Imaging, Cell 174(4): 968-981 (Aug. 2018). [cited by applicant]