机器学习应用与选择生物学特征的脑肿瘤分类:迈向一个新的诊断机制

Krishnendu Ghosh
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摘要

组织病理学分类的低级别脑肿瘤表现出重叠的生物学特征,使其难以区分。在目前的研究中,通过机器学习技术训练了三种不同组织病理类型的低级别脑肿瘤患者样本,并使用选择的特征进行分类。我们具体使用肿瘤标志物的基本增殖、侵袭、巨噬细胞浸润三角形,以碘化丙酸(PI)标记的细胞周期、Ki67标记的增殖指数、MMP2表达的侵袭、银金染色巨噬细胞/小胶质细胞的存在、CD11b+和Iba1+细胞的存在作为生物学参数。当使用适当的机器学习协议通过提取底层特征并在二维可感知空间中表示这些参数时,发现这些参数能够区分肿瘤类型。通过统计学习理论对这些参数在六维特征空间中提取的特征进行训练,支持向量机(SVM)最大限度地提高其预测精度。采用LOO交叉验证法判断训练结果的准确性,然后采用自编码器(AE)将特征维数降至视觉可感知的二维。从标准方法量化的生物学特征来看,无法区分三种低级别脑肿瘤。然而,当使用AE将六维特征空间降维为二维时,经过SVM和LOO交叉验证训练后,特征组合输出在该二维空间中呈现出清晰的分区。这表明,当通过适当的支持向量机训练并从多维空间减少到二维空间时,这些肿瘤类型的重叠生物学特征可以使用共同的生物学特征组合提供明确的病理-临床分类优势。因此,机器学习应用程序可能被用作传统实践的补充诊断协议。
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Brain Tumour Classification by Machine Learning Applications with Selected Biological Features: Towards A Newer Diagnostic Regime
: Histopathologically classified low-grade brain tumours show overlapping biological characteristics making them difficult to distinguish. In the present study low-grade brain tumour patient samples of three different histopathological types have been trained through machine learning technique using selected features for its classification. We used specifically the fundamental proliferation, invasion, macrophage infiltration triangle of cancer hallmark with propidium iodide (PI) marked cell-cycle, Ki67 marked proliferative indexing, invasion with MMP2 expression and presence of macrophage/microglia by silver-gold staining, CD11b+ and Iba1+ cell presence as biological parameters. These parameters when trained with proper machine learning protocol through extraction of underling features and represented in a 2D perceivable space are found capable of distinguishing the tumour types. Extracted features from such parameters in a six-dimensional featured space were trained through statistical learning theory while support vector machine (SVM) maximizes their predictive precision. The leave one out (LOO) cross validation process was applied to judge the accuracy of training followed by auto-encoder (AE) to reduce feature dimension at two which is visually perceptible. From the biological features quantified with standard methods it was found impossible to demarcate the three types of low grade brain tumours. However, after training through SVM and LOO cross validation when the six- dimensional featured space had been reduced into two-dimension using AE, the combined output of the features showed clear zonation in that 2D space. This indicates that the overlapping biological characteristics of these tumour types, when trained through proper support vector machine and reduced from multiple to two dimensional space provides a clear patho-clinical classification edge using a combination of common biological features. Hence, machine learning applications may potentially be used as a complementary diagnostic protocol with the conventional practice.
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