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Multi-Instance Multi-Label Learning for Gene Mutation Prediction in Hepatocellular Carcinoma

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 Added by Ziyuan Zhao
 Publication date 2020
and research's language is English




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Gene mutation prediction in hepatocellular carcinoma (HCC) is of great diagnostic and prognostic value for personalized treatments and precision medicine. In this paper, we tackle this problem with multi-instance multi-label learning to address the difficulties on label correlations, label representations, etc. Furthermore, an effective oversampling strategy is applied for data imbalance. Experimental results have shown the superiority of the proposed approach.



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Hepatocellular carcinoma (HCC) is the most common type of primary liver cancer and the fourth most common cause of cancer-related death worldwide. Understanding the underlying gene mutations in HCC provides great prognostic value for treatment planning and targeted therapy. Radiogenomics has revealed an association between non-invasive imaging features and molecular genomics. However, imaging feature identification is laborious and error-prone. In this paper, we propose an end-to-end deep learning framework for mutation prediction in APOB, COL11A1 and ATRX genes using multiphasic CT scans. Considering intra-tumour heterogeneity (ITH) in HCC, multi-region sampling technology is implemented to generate the dataset for experiments. Experimental results demonstrate the effectiveness of the proposed model.
In this paper, we propose the MIML (Multi-Instance Multi-Label learning) framework where an example is described by multiple instances and associated with multiple class labels. Compared to traditional learning frameworks, the MIML framework is more convenient and natural for representing complicated objects which have multiple semantic meanings. To learn from MIML examples, we propose the MimlBoost and MimlSvm algorithms based on a simple degeneration strategy, and experiments show that solving problems involving complicated objects with multiple semantic meanings in the MIML framework can lead to good performance. Considering that the degeneration process may lose information, we propose the D-MimlSvm algorithm which tackles MIML problems directly in a regularization framework. Moreover, we show that even when we do not have access to the real objects and thus cannot capture more information from real objects by using the MIML representation, MIML is still useful. We propose the InsDif and SubCod algorithms. InsDif works by transforming single-instances into the MIML representation for learning, while SubCod works by transforming single-label examples into the MIML representation for learning. Experiments show that in some tasks they are able to achieve better performance than learning the single-instances or single-label examples directly.
Multi-typed objects Multi-view Multi-instance Multi-label Learning (M4L) deals with interconnected multi-typed objects (or bags) that are made of diverse instances, represented with heterogeneous feature views and annotated with a set of non-exclusive but semantically related labels. M4L is more general and powerful than the typical Multi-view Multi-instance Multi-label Learning (M3L), which only accommodates single-typed bags and lacks the power to jointly model the naturally interconnected multi-typed objects in the physical world. To combat with this novel and challenging learning task, we develop a joint matrix factorization based solution (M4L-JMF). Particularly, M4L-JMF firstly encodes the diverse attributes and multiple inter(intra)-associations among multi-typed bags into respective data matrices, and then jointly factorizes these matrices into low-rank ones to explore the composite latent representation of each bag and its instances (if any). In addition, it incorporates a dispatch and aggregation term to distribute the labels of bags to individual instances and reversely aggregate the labels of instances to their affiliated bags in a coherent manner. Experimental results on benchmark datasets show that M4L-JMF achieves significantly better results than simple adaptions of existing M3L solutions on this novel problem.
Aspect-category sentiment analysis (ACSA) aims to predict sentiment polarities of sentences with respect to given aspect categories. To detect the sentiment toward a particular aspect category in a sentence, most previous methods first generate an aspect category-specific sentence representation for the aspect category, then predict the sentiment polarity based on the representation. These methods ignore the fact that the sentiment of an aspect category mentioned in a sentence is an aggregation of the sentiments of the words indicating the aspect category in the sentence, which leads to suboptimal performance. In this paper, we propose a Multi-Instance Multi-Label Learning Network for Aspect-Category sentiment analysis (AC-MIMLLN), which treats sentences as bags, words as instances, and the words indicating an aspect category as the key instances of the aspect category. Given a sentence and the aspect categories mentioned in the sentence, AC-MIMLLN first predicts the sentiments of the instances, then finds the key instances for the aspect categories, finally obtains the sentiments of the sentence toward the aspect categories by aggregating the key instance sentiments. Experimental results on three public datasets demonstrate the effectiveness of AC-MIMLLN.
Motivation: Histone modifications are among the most important factors that control gene regulation. Computational methods that predict gene expression from histone modification signals are highly desirable for understanding their combinatorial effects in gene regulation. This knowledge can help in developing epigenetic drugs for diseases like cancer. Previous studies for quantifying the relationship between histone modifications and gene expression levels either failed to capture combinatorial effects or relied on multiple methods that separate predictions and combinatorial analysis. This paper develops a unified discriminative framework using a deep convolutional neural network to classify gene expression using histone modification data as input. Our system, called DeepChrome, allows automatic extraction of complex interactions among important features. To simultaneously visualize the combinatorial interactions among histone modifications, we propose a novel optimization-based technique that generates feature pattern maps from the learnt deep model. This provides an intuitive description of underlying epigenetic mechanisms that regulate genes. Results: We show that DeepChrome outperforms state-of-the-art models like Support Vector Machines and Random Forests for gene expression classification task on 56 different cell-types from REMC database. The output of our visualization technique not only validates the previous observations but also allows novel insights about combinatorial interactions among histone modification marks, some of which have recently been observed by experimental studies.

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