Identification and model construction of survival-associated proteins for pancreatic cancer based on deep learning

IF 6.2 2区 计算机科学 Q1 COMPUTER SCIENCE, THEORY & METHODS Future Generation Computer Systems-The International Journal of Escience Pub Date : 2024-07-17 DOI:10.1016/j.future.2024.07.023
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Abstract

Pancreatic cancer (PC) is a malignancy typified by its insidious onset, rapid progression, limited resectability, poor treatment response, and exceedingly dismal prognosis. The transition from precursor lesions to infiltrating malignant tumors in pancreatic cancer is concomitant with the accrual of genetic mutations. The elucidation of proteins linked to the prognosis of pancreatic cancer holds paramount importance in the realm of pancreatic cancer management. Herein, we introduce DeepPCSA, a model tailored for the screening of target proteins and the prediction of survival time, employing both conventional methodologies and deep learning techniques for patient survival analysis. This framework leverages the LASSOCOX regression approach on differentially expressed genes (DEGs) to discern pivotal genes, succeeded by the development of a prognostic model employing convolutional and fully connected layers to prognosticate patient survival duration. Furthermore, we account for covariates such as age, gender, and other pertinent factors for independent prognostic scrutiny, affirming the autonomy of our model as a prognostic determinant. Employing unsupervised clustering methodologies, we delineated two molecular subtypes delineated by disparate biological processes. Ultimately, via drug sensitivity analysis, we delineated the interrelation between survival duration and pharmaceuticals, substantiating the necessity for tailored drug interventions catering to patients of varying risk strata.

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基于深度学习的胰腺癌生存相关蛋白的鉴定与模型构建
胰腺癌(PC)是一种发病隐匿、进展迅速、可切除性有限、治疗反应差、预后极差的恶性肿瘤。胰腺癌从前驱病变转变为浸润性恶性肿瘤的过程伴随着基因突变的累积。阐明与胰腺癌预后相关的蛋白质对胰腺癌的治疗至关重要。在此,我们介绍 DeepPCSA,这是一种为筛选目标蛋白质和预测生存时间而量身定制的模型,采用了传统方法和深度学习技术来分析患者的生存情况。该框架利用对差异表达基因(DEGs)的 LASSOCOX 回归方法来识别关键基因,然后利用卷积层和全连接层开发预后模型,以预测患者的生存期。此外,我们还考虑了年龄、性别等协变量和其他相关因素,以进行独立的预后审查,从而肯定了我们的模型作为预后决定因素的自主性。利用无监督聚类方法,我们划定了由不同生物过程划分的两种分子亚型。最后,通过药物敏感性分析,我们确定了存活时间与药物之间的相互关系,从而证明了针对不同风险阶层的患者采取有针对性的药物干预措施的必要性。
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来源期刊
CiteScore
19.90
自引率
2.70%
发文量
376
审稿时长
10.6 months
期刊介绍: Computing infrastructures and systems are constantly evolving, resulting in increasingly complex and collaborative scientific applications. To cope with these advancements, there is a growing need for collaborative tools that can effectively map, control, and execute these applications. Furthermore, with the explosion of Big Data, there is a requirement for innovative methods and infrastructures to collect, analyze, and derive meaningful insights from the vast amount of data generated. This necessitates the integration of computational and storage capabilities, databases, sensors, and human collaboration. Future Generation Computer Systems aims to pioneer advancements in distributed systems, collaborative environments, high-performance computing, and Big Data analytics. It strives to stay at the forefront of developments in grids, clouds, and the Internet of Things (IoT) to effectively address the challenges posed by these wide-area, fully distributed sensing and computing systems.
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