Uncovering key molecular mechanisms in the early and late-stage of papillary thyroid carcinoma using association rule mining algorithm.

OBJECTIVE: Thyroid Cancer (TC) is the most frequent endocrine malignancy neoplasm. It is the sixth cause of cancer in women worldwide. The treatment process could be expedited by identifying the controlling molecular mechanisms at the early and late stages, which can contribute to the acceleration of treatment schemes and the improvement of patient survival outcomes. In this work, we study the significant mRNAs through Machine Learning Algorithms in both the early and late stages of Papillary Thyroid Cancer (PTC). METHOD: During the course of our study, we investigated various methods and techniques to obtain suitable results. The sequence of procedures we followed included organizing data, using nested cross-validation, data cleaning, and normalization at the initial stage. Next, to apply feature selection, a t-test and binary Non-Dominated Sorting Genetic Algorithm II (NSGAII) were chosen to be employed. Later on, during the analysis stage, the discriminative power of the selected features was evaluated using machine learning and deep learning algorithms. Finally, we considered the selected features and utilized Association Rule Mining algorithm to identify the most important ones for improving the decoding of dominant molecular mechanisms in PTC through its early and late stages. RESULT: The SVM classifier was able to distinguish between early and late-stage categories with an accuracy of 83.5% and an AUC of 0.78 based on the identified mRNAs. The most significant genes associated with the early and late stages of PTC were identified as (e.g., ZNF518B, DTD2, CCAR1) and (e.g., lnc-DNAJB6-7:7, RP11-484D2.3, MSL3P1), respectively. CONCLUSION: Current study reveals a clear picture of the potential candidate genes that could play a major role not only in the early stage, but also throughout the late one. Hence, the findings could be of help to identify therapeutic targets for more effective PTC drug developments.

Unraveling the link between PTBP1 and severe asthma through machine learning and association rule mining method.

Severe asthma is a chronic inflammatory airway disease with great therapeutic challenges. Understanding the genetic and molecular mechanisms of severe asthma may help identify therapeutic strategies for this complex condition. RNA expression data were analyzed using a combination of artificial intelligence methods to identify novel genes related to severe asthma. Through the ANOVA feature selection approach, 100 candidate genes were selected among 54,715 mRNAs in blood samples of patients with severe asthmatic and healthy groups. A deep learning model was used to validate the significance of the candidate genes. The accuracy, F1-score, AUC-ROC, and precision of the 100 genes were 83%, 0.86, 0.89, and 0.9, respectively. To discover hidden associations among selected genes, association rule mining was applied. The top 20 genes including the PTBP1, RAB11FIP3, APH1A, and MYD88 were recognized as the most frequent items among severe asthma association rules. The PTBP1 was found to be the most frequent gene associated with severe asthma among those 20 genes. PTBP1 was the gene most frequently associated with severe asthma among candidate genes. Identification of master genes involved in the initiation and development of asthma can offer novel targets for its diagnosis, prognosis, and targeted-signaling therapy.

Key therapeutic targets implicated at the early stage of hepatocellular carcinoma identified through machine-learning approaches.

Hepatocellular carcinoma (HCC) is the most frequent type of primary liver cancer. Early-stage detection plays an essential role in making treatment decisions and identifying dominant molecular mechanisms. We utilized machine learning algorithms to find significant mRNAs and microRNAs (miRNAs) at the early and late stages of HCC. First, pre-processing approaches, including organization, nested cross-validation, cleaning, and normalization were applied. Next, the t-test/ANOVA methods and binary particle swarm optimization were used as a filter and wrapper method in the feature selection step, respectively. Then, classifiers, based on machine learning and deep learning algorithms were utilized to evaluate the discrimination power of selected features (mRNAs and miRNAs) in the classification step. Finally, the association rule mining algorithm was applied to selected features for identifying key mRNAs and miRNAs that can help decode dominant molecular mechanisms in HCC stages. The applied methods could identify key genes associated with the early (e.g., Vitronectin, thrombin-activatable fibrinolysis inhibitor, lactate dehydrogenase D (LDHD), miR-590) and late-stage (e.g., SPRY domain containing 4, regucalcin, miR-3199-1, miR-194-2, miR-4999) of HCC. This research could establish a clear picture of putative candidate genes, which could be the main actors at the early and late stages of HCC.