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博碩士論文 etd-1119120-175136 詳細資訊
Title page for etd-1119120-175136
論文名稱
Title
以SMILES結構增強二元屬性資料之藥物副作用預測
Using SMILES structure to enhance the prediction of drug side effect
系所名稱
Department
畢業學年期
Year, semester
語文別
Language
學位類別
Degree
頁數
Number of pages
65
研究生
Author
指導教授
Advisor
召集委員
Convenor
口試委員
Advisory Committee
口試日期
Date of Exam
2020-12-04
繳交日期
Date of Submission
2020-12-19
關鍵字
Keywords
一維卷積網路、SMILES、多模態模型、深度學習、藥物副作用預測
deep learning, multi-model neural networks, 1-dimension convolutional neural networks, drug side-effect prediction, SMILES
統計
Statistics
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中文摘要
藥物開發研究一直受到高度的關注,不管是治療所需的藥物,亦或是預防性的疫苗,人類在用藥的需求只會隨著醫療知識的進步不斷提高,然而開發的過程是冗長且每一個步驟都必須非常謹慎的,以免用藥變成用毒,沒解決問題反而損害身體。儘管開發過程順利且按照規章流程,但是每年還是有許多用藥人受到副作用的影響,嚴重者甚至死亡,例如近期在韓國施打的賽諾菲(Sanofi)流感疫苗,統計到10月底已經死亡83人。如此高開發成本的條件下,副作用問題仍然層出不窮,導致更多的醫療資源被浪費,所以如何有效地找出潛在副作用變成藥物開發不可或缺的步驟。
在網路普及後資料更容易被收集與整合,藥物相關資料也越來越豐富且多元,然而現今的研究大多還是以某種資料搭配特定的模型訓練,所以本研究主要探討利用不同的模型來萃取不同型態或種類的資料,以提高副作用的預測能力。除了使用多模態模型外,本研究為了改善藥物資料不平衡的問題,將藥物以已知副作用的數量區分成兩個模型訓練,避免整個訓練被部分極度不平衡的資料影響。最後實驗研究過程中,發現大部分的論文並沒有針對雙字元素作特別的編碼,例如鈉(Na)、氯(Cl)、鈣(Ca),這樣會混淆萃取出的特徵與副作用之間的關聯,所以本研究也有調整編碼方式,讓雙字元素可以正確被編碼。就實驗結果而言,多模態模型的預測能力比個別訓練的模型還要好,在資料依照副作用數量分段訓練後,相對平衡的資料其訓練後預測結果也提升不少,而調整雙字元素的編碼後,盡管就數據上只有其中一個資料集搭配特定模型有顯著影響,但是在資料量增加後可能會有更明顯的效果,這部份值得探討。
另外在實驗過程中發現利用已知副作用來預測未知副作用可以得到最好的結果,證明副作用之間可能是有高度關聯的且高機率併發的,這部分也值得繼續研究。
Abstract
Drug development research has always received considerable amount of attention. With the advancement of knowledge in the medical field, human demand for medicines either in the form of drugs for treatment or preventive vaccines will continue to increase. However, it must be ensured that medicines do not become poisons and damage the body instead of curing the ailment. Therefore, most drug development processes are lengthy, and every step in such processes must be performed with utmost care. Although development processes may be smooth and in accordance with regulations, several drug users continue to be adversely affected by side effects every year. In severe cases, the side effects can be fatal. For example, the recent Sanofi flu vaccine that was administered in South Korea has caused 83 deaths till the end of October 2020. Despite the high development costs of the drug, its side effects continue to emerge, causing enormous wastage of medical resources. As a result, effective identification of potential side effects have become an indispensable step in drug development.
Owing to the popularity of the Internet, data are now easier to collect and integrate. Drug-related information is becoming increasingly abundant and diverse. Nevertheless, most of the current research still uses specific data with specific model training. To this end, this study mainly explores the use of different models to extract different types of data to improve the predictive ability of the drug side effects. In addition to using multi-model neural networks, this study aims to improve the imbalance of drug data. In this study, drugs are divided into two training models based on the number of known side effects to avoid the entire training being affected by some extremely unbalanced data. Finally, during experimental research, it was found that most of the studies did not specifically encode for double-character elements, such as sodium (Na), chlorine (Cl), and calcium (Ca). This leads to a confusion in the relationship between the extracted features and the side effects. In order to solve the problem, my model will adjust the encoding method so that double-word elements can be encoded correctly. In terms of experimental results, the predictive ability of multi-model neural networks is better than that of the individually trained single model. After the data are trained in segments according to the number of side effects, the prediction results of even relatively balanced data improve significantly. Furthermore, after adjusting the encoding of double-character elements, it was seen that only one of the datasets on the data had a significant impact on the specific model. Although the results did not show significant improvement, they may do so with an increased amount of data. This part is worth exploring.
Moreover, it was revealed during the experiment that using known side effects to predict unknown side effects can yield the best results. This proves that side effects may be highly correlated and may have a high probability of being concurrent. This part is also worth studying.
目次 Table of Contents
論文審定書 i
致謝 ii
摘要 iii
Abstract iv
目錄 vi
圖次 viii
表次 x
第一章、 緒論 1
1.1 研究背景 1
1.2 研究動機與目的 4
1.3 研究貢獻 5
第二章、 文獻探討 6
2.1 深度學習(Deep Learning, DL) 6
2.1.1 多層感知器(Multilayer Perceptron, MLP) 6
2.1.2 卷積神經網路(Convolutional neural networks, CNN) 7
2.1.3 遞迴神經網路(Recurrent Neural Networks, RNN) 8
2.1.4 長短期記憶模型(Long Short-Term Memory, LSTM) 8
2.1.5 多模態神經網路(Multi-Model Neural Networks, MMNN) 9
2.2 藥物結構使用 9
2.3 藥物副作用預測 12
2.3.1 單標籤副作用預測 12
2.3.2 多標籤副作用預測 13
第三章、 研究方法 20
3.1 資料取得與處理 20
3.2 標籤不平衡處理 21
3.3 多層感知器(Multilayer Perceptron, MLP) 22
3.4 卷積神經網路(Convolutional Neural Networks, CNN) 23
3.5 多模態神經網路(Multi-Model Neural Networks, MMNN) 25
3.6 已知副作用預測未知副作用 28
第四章、 研究結果 31
4.1 實驗參數設置 31
4.2 資料觀察 32
4.3 多層感知器(Multilayer Perceptron, MLP) 33
4.4 卷積神經網路(Convolutional Neural Networks, CNN) 34
4.5 模型的分段與融合 37
4.6 已知副作用預測潛在未知副作用 40
第五章、 結論 45
5.1 總結 45
5.2 未來展望 46
參考文獻 48
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