Chinju John, Jayakrushna Sahoo, Irish K. Sajan, Manu Madhavan, Oommen K. Mathew
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引用次数: 0
摘要
根据蛋白质序列对蛋白质家族进行分类是蛋白质组学及相关研究中的一项长期任务。为了应对这一挑战,人们建立了大量深度学习模型,但由于其黑箱特性,这些模型在可靠性方面仍有不足。在这里,我们提出了一种新颖的可解释性管道,用于解释深度学习模型在真核生物激酶组分类中的关键决策。基于对最前沿深度学习算法的比较和实验分析,我们选择了最佳深度学习模型 CNN-BLSTM,将八个真核生物激酶序列归入其相应的家族。作为对基于 CNN 的模型在该领域中基于类激活图的传统解释的替代,我们将 GRAD CAM 和集成梯度(IG)可解释性的工作方式进行了级联,以获得更好、更负责任的结果。为了确保分类器的可信度,我们屏蔽了从可解释性管道中识别出的激酶领域踪迹,并观察到特定类别的 F1 分数从 0.96 降至 0.76。根据可解释人工智能范式,我们的研究结果很有希望,有助于提高深度学习模型在生物序列相关研究中的可信度。
CNN-BLSTM based deep learning framework for eukaryotic kinome classification: An explainability based approach
Classification of protein families from their sequences is an enduring task in Proteomics and related studies. Numerous deep-learning models have been moulded to tackle this challenge, but due to the black-box character, they still fall short in reliability. Here, we present a novel explainability pipeline that explains the pivotal decisions of the deep learning model on the classification of the Eukaryotic kinome. Based on a comparative and experimental analysis of the most cutting-edge deep learning algorithms, the best deep learning model CNN-BLSTM was chosen to classify the eight eukaryotic kinase sequences to their corresponding families. As a substitution for the conventional class activation map-based interpretation of CNN-based models in the domain, we have cascaded the GRAD CAM and Integrated Gradient (IG) explainability modus operandi for improved and responsible results. To ensure the trustworthiness of the classifier, we have masked the kinase domain traces, identified from the explainability pipeline and observed a class-specific drop in F1-score from 0.96 to 0.76. In compliance with the Explainable AI paradigm, our results are promising and contribute to enhancing the trustworthiness of deep learning models for biological sequence-associated studies.
期刊介绍:
Computational Biology and Chemistry publishes original research papers and review articles in all areas of computational life sciences. High quality research contributions with a major computational component in the areas of nucleic acid and protein sequence research, molecular evolution, molecular genetics (functional genomics and proteomics), theory and practice of either biology-specific or chemical-biology-specific modeling, and structural biology of nucleic acids and proteins are particularly welcome. Exceptionally high quality research work in bioinformatics, systems biology, ecology, computational pharmacology, metabolism, biomedical engineering, epidemiology, and statistical genetics will also be considered.
Given their inherent uncertainty, protein modeling and molecular docking studies should be thoroughly validated. In the absence of experimental results for validation, the use of molecular dynamics simulations along with detailed free energy calculations, for example, should be used as complementary techniques to support the major conclusions. Submissions of premature modeling exercises without additional biological insights will not be considered.
Review articles will generally be commissioned by the editors and should not be submitted to the journal without explicit invitation. However prospective authors are welcome to send a brief (one to three pages) synopsis, which will be evaluated by the editors.