Cell Discovery| 蛋白质组学+人工智能| 基于蛋白质的甲状腺结节人工智能分类器-CSDN博客

本文链接：https://blog.csdn.net/weixin_45822007/article/details/128024729

COVER

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Sun Y, Selvarajan S, Zang Z, et al. Artificial intelligence defines protein-based classification of thyroid nodules [published correction appears in Cell Discov. 2022 Sep 30;8(1):100]. Cell Discov. 2022;8(1):85. Published 2022 Sep 6. doi:10.1038/s41421-022-00442-x
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论文通讯为西湖大学郭天南和李子青，分别是组学和AI领域的大佬。
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Abstract

作者开发一种「AI-defined protein-based biomarker panel」用于甲状腺结节诊断分类。最初基于福尔马林固定石蜡包埋(formalin-fixed paraffin-embedded，FFPE)样本，进一步改进为微量细针穿刺(fine-needle aspiration，FNA)组织标本。作者首先开发了一个基于1724个「FFPE」甲状腺组织样本的蛋白质组的19个蛋白质生物标记的「神经网络模型」。该分类器在分类恶性甲状腺结节的发现集中达到91%以上的准确性。在288个结节的回顾性队列中，通过盲法分析对分类器进行了外部验证(准确率89%;FFPE)和来自12个独立临床中心的294例FNA活检(准确率85%)的前瞻性队列。

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神经网络模型的代码作者已开源，有兴趣的同学可以自行去原文查看链接。当然，如果大家需要木舟对代码进行注释复现，可以多多「点赞」、「在看」和「分享」本文。
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The project design and workflow of the FFPE-PCT-DIA pipeline

image-20221113214941483

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主要流程还是比较简单的，这里就不赘述。
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Feature selection and classifier development

其他部分都比较常规，直接看一下模型部分。

Schematic workflow

特征选择

Data splitting

如图，将「发现队列」（discovery dataset）分为2/3的datasetA和剩下的datasetB。在datasetA中使用三折交叉验证（three-fold cross-validation）进行特征筛选（Feature selection）。

Flow diagram of genetic algorithm for protein features selection

根据「差异分析结果」以及「已发表文献报道」或TCGA、OMIM数据库分析与甲状腺癌诊断有关的蛋白，将原始的6689个蛋白筛选到1302个。再根据样本缺失率<35%，得到767个蛋白质。

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35%缺失率阈值怎么确定的？

In process of feature selection, we explored different screening conditions, using 25%,30%,35%, and 40% as thresholds for the missing value. The data showed that at more relaxed screening conditions the higher number of candidate features were nominated and that the results became more unstable in the independent validation set. The features with higher missing value rates, although potentially providing better classification were not stably detected and may negatively affect the quality of the model if such features are selected. Finally, in our classifier, we clearly defined the criteria for feature selection and used 767 proteins that were missing in less than 35% of samples
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随机生成500个每个包含19个蛋白（图中有误）的panel，在datasetA中进行交叉验证，并计算fitness。datasetB对性能进行评估，选出最优panel。

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为了消除seed人为设置的随机性，作者比较了seed从0取到14对特征筛选的影响。
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为什么选择19个蛋白：

To determine the count of protein features in the panel, we compare the model performances on the different number of features from four to 35 proteins. The more features the better accuracy and AUC achieved and reached a plateau when using 13 proteins . But for the most similar two histopathology types, FA and FTC, 19 proteins achieved the highest accuracy. Therefore, we used 19 proteins as a panel in the present study.

line chart showing the model performance on different counts of protein features
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