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1.
Nat Commun ; 15(1): 5700, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38972896

RESUMO

Identifying spatially variable genes (SVGs) is crucial for understanding the spatiotemporal characteristics of diseases and tissue structures, posing a distinctive challenge in spatial transcriptomics research. We propose HEARTSVG, a distribution-free, test-based method for fast and accurately identifying spatially variable genes in large-scale spatial transcriptomic data. Extensive simulations demonstrate that HEARTSVG outperforms state-of-the-art methods with higher F 1 scores (average F 1 Score=0.948), improved computational efficiency, scalability, and reduced false positives (FPs). Through analysis of twelve real datasets from various spatial transcriptomic technologies, HEARTSVG identifies a greater number of biologically significant SVGs (average AUC = 0.792) than other comparative methods without prespecifying spatial patterns. Furthermore, by clustering SVGs, we uncover two distinct tumor spatial domains characterized by unique spatial expression patterns, spatial-temporal locations, and biological functions in human colorectal cancer data, unraveling the complexity of tumors.


Assuntos
Perfilação da Expressão Gênica , Transcriptoma , Humanos , Perfilação da Expressão Gênica/métodos , Neoplasias Colorretais/genética , Biologia Computacional/métodos , Algoritmos , Regulação Neoplásica da Expressão Gênica , Simulação por Computador , Bases de Dados Genéticas
2.
Cell Rep Med ; 5(5): 101536, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38697103

RESUMO

Spatial transcriptomics (ST) provides insights into the tumor microenvironment (TME), which is closely associated with cancer prognosis, but ST has limited clinical availability. In this study, we provide a powerful deep learning system to augment TME information based on histological images for patients without ST data, thereby empowering precise cancer prognosis. The system provides two connections to bridge existing gaps. The first is the integrated graph and image deep learning (IGI-DL) model, which predicts ST expression based on histological images with a 0.171 increase in mean correlation across three cancer types compared with five existing methods. The second connection is the cancer prognosis prediction model, based on TME depicted by spatial gene expression. Our survival model, using graphs with predicted ST features, achieves superior accuracy with a concordance index of 0.747 and 0.725 for The Cancer Genome Atlas breast cancer and colorectal cancer cohorts, outperforming other survival models. For the external Molecular and Cellular Oncology colorectal cancer cohort, our survival model maintains a stable advantage.


Assuntos
Aprendizado Profundo , Neoplasias , Microambiente Tumoral , Humanos , Prognóstico , Neoplasias/patologia , Neoplasias/genética , Neoplasias/diagnóstico , Transcriptoma/genética , Regulação Neoplásica da Expressão Gênica , Feminino , Neoplasias da Mama/patologia , Neoplasias da Mama/genética , Neoplasias da Mama/diagnóstico
3.
Cancer Sci ; 114(2): 690-701, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36114747

RESUMO

Accurately predicting patient survival is essential for cancer treatment decision. However, the prognostic prediction model based on histopathological images of stomach cancer patients is still yet to be developed. We propose a deep learning-based model (MultiDeepCox-SC) that predicts overall survival in patients with stomach cancer by integrating histopathological images, clinical data, and gene expression data. The MultiDeepCox-SC not only automatedly selects patches with more information for survival prediction, without manual labeling for histopathological images, but also identifies genetic and clinical risk factors associated with survival in stomach cancer. The prognostic accuracy of the MultiDeepCox-SC (C-index = 0.744) surpasses the result only based on histopathological image (C-index = 0.660). The risk score of our model was still an independent predictor of survival outcome after adjustment for potential confounders, including pathologic stage, grade, age, race, and gender on The Cancer Genome Atlas dataset (hazard ratio 1.555, p = 3.53e-08) and the external test set (hazard ratio 2.912, p = 9.42e-4). Our fully automated online prognostic tool based on histopathological images, clinical data, and gene expression data could be utilized to improve pathologists' efficiency and accuracy (https://yu.life.sjtu.edu.cn/DeepCoxSC).


Assuntos
Aprendizado Profundo , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/genética , Prognóstico , Fatores de Risco
4.
J Hematol Oncol ; 14(1): 154, 2021 09 26.
Artigo em Inglês | MEDLINE | ID: mdl-34565412

RESUMO

BACKGROUND: Liver cancer remains the leading cause of cancer death globally, and the treatment strategies are distinct for each type of malignant hepatic tumors. However, the differential diagnosis before surgery is challenging and subjective. This study aims to build an automatic diagnostic model for differentiating malignant hepatic tumors based on patients' multimodal medical data including multi-phase contrast-enhanced computed tomography and clinical features. METHODS: Our study consisted of 723 patients from two centers, who were pathologically diagnosed with HCC, ICC or metastatic liver cancer. The training set and the test set consisted of 499 and 113 patients from center 1, respectively. The external test set consisted of 111 patients from center 2. We proposed a deep learning model with the modular design of SpatialExtractor-TemporalEncoder-Integration-Classifier (STIC), which take the advantage of deep CNN and gated RNN to effectively extract and integrate the diagnosis-related radiological and clinical features of patients. The code is publicly available at https://github.com/ruitian-olivia/STIC-model . RESULTS: The STIC model achieved an accuracy of 86.2% and AUC of 0.893 for classifying HCC and ICC on the test set. When extended to differential diagnosis of malignant hepatic tumors, the STIC model achieved an accuracy of 72.6% on the test set, comparable with the diagnostic level of doctors' consensus (70.8%). With the assistance of the STIC model, doctors achieved better performance than doctors' consensus diagnosis, with an increase of 8.3% in accuracy and 26.9% in sensitivity for ICC diagnosis on average. On the external test set from center 2, the STIC model achieved an accuracy of 82.9%, which verify the model's generalization ability. CONCLUSIONS: We incorporated deep CNN and gated RNN in the STIC model design for differentiating malignant hepatic tumors based on multi-phase CECT and clinical features. Our model can assist doctors to achieve better diagnostic performance, which is expected to serve as an AI assistance system and promote the precise treatment of liver cancer.


Assuntos
Carcinoma Hepatocelular/diagnóstico por imagem , Neoplasias Hepáticas/diagnóstico por imagem , Fígado/diagnóstico por imagem , Aprendizado Profundo , Diagnóstico por Computador , Diagnóstico Diferencial , Humanos , Tomografia Computadorizada por Raios X
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