本研究旨在通過系統生物學和參數估計方法，結合大數據挖掘和全基因組微陣列數據，來估算蛋白質-蛋白質相互作用網路（PPIN）和基因調控網路（GRN），以構建異位性皮膚炎（AD）和健康對照組的全基因組遺傳與表觀遺傳網路（GWGEN）。隨後，利用主網路投影（PNP）方法從實際的GWGEN中提取AD和健康對照組的核心GWGEN，並進行京都基因與基因組百科全書（KEGG）通路註釋。接著，我們比較AD和健康對照組核心信號通路之間的異常信號通路，探討AD的發病機制。然後，我們從異常核心信號通路中選取了作為AD治療靶點的生物標誌物，如IL-1β、GATA3、Akt和NF-κB，這些標誌物在對下游基因的異常調控中起著重要作用，導致AD患者的細胞功能失調。接下來，我們使用藥物-靶點相互作用（DTI）數據庫對基於深度神經網路（DNN）的DTI模型進行預訓練，以預測這些生物標誌物的互動分子藥物。因此，我們獲得了可能與藥物標靶相互作用的候選分子藥物。最後，根據藥物毒性、敏感性和調控能力等藥物設計規範，篩選出潛在的分子藥物作為治療這些生物標誌物的選項，包括二甲雙胍、尿囊素和U-0126，這些藥物在調節異常免疫反應和恢復AD病理信號通路方面顯示出潛在的治療效果。

This study aimed to estimate the protein-protein interaction network (PPIN) and gene regulatory network (GRN) to construct real genome-wide genetic and epigenetic network (GWGEN) of Atopic dermatitis (AD) and healthy controls through systems biology and parameter estimation method by big data mining and their genome-wide microarray data. Subsequently, core GWGENs of AD and healthy control are extracted from their real GWGENs by principal network projection (PNP) method for Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway annotation. Then, we compare the abnormal signaling pathways between core signaling pathways of AD and healthy control to investigate pathogenesis of AD. Then, we selected biomarkers of AD as drug targets for treating AD from the abnormal core signaling pathways, such as IL-1β, GATA3, Akt, and NF-κB, which play important roles in the abnormal regulations on the downstream genes, leading to cellular dysfunctions in AD patients. Next, a deep neural network (DNN)-based drug-target interaction (DTI) model is pre-trained by Drug-Target Interaction (DTI) databases to predict the interactive molecular drugs for these biomarkers. Consequently, we obtained a list of candidate molecular drugs, which could to interact with the target molecules. Finally, we screened the candidate molecular drugs based on drug toxicity, sensitivity, and regulatory ability as drug design specifications to select potential molecular drugs for these biomarkers to treat AD, including metformin, allantoin, and U-0126, which have showed potential therapeutic treatment on regulating abnormal immune responses and restoring pathogenic signaling pathways of AD.

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