Integrative approach of omics and imaging data to discover new insights for understanding brain diseases.

Treatments that can completely resolve brain diseases have yet to be discovered. Omics is a novel technology that allows researchers to understand the molecular pathways underlying brain diseases. Multiple omics, including genomics, transcriptomics and proteomics, and brain imaging technologies, such as MRI, PET and EEG, have contributed to brain disease-related therapeutic target detection. However, new treatment discovery remains challenging. We focused on establishing brain multi-molecular maps using an integrative approach of omics and imaging to provide insights into brain disease diagnosis and treatment. This approach requires precise data collection using omics and imaging technologies, data processing and normalization. Incorporating a brain molecular map with the advanced technologies through artificial intelligence will help establish a system for brain disease diagnosis and treatment through regulation at the molecular level.

Multi-proteomic analyses of 5xFAD mice reveal new molecular signatures of early-stage Alzheimer's disease.

An early diagnosis of Alzheimer's disease is crucial as treatment efficacy is limited to the early stages. However, the current diagnostic methods are limited to mid or later stages of disease development owing to the limitations of clinical examinations and amyloid plaque imaging. Therefore, this study aimed to identify molecular signatures including blood plasma extracellular vesicle biomarker proteins associated with Alzheimer's disease to aid early-stage diagnosis. The hippocampus, cortex, and blood plasma extracellular vesicles of 3- and 6-month-old 5xFAD mice were analyzed using quantitative proteomics. Subsequent bioinformatics and biochemical analyses were performed to compare the molecular signatures between wild type and 5xFAD mice across different brain regions and age groups to elucidate disease pathology. There was a unique signature of significantly altered proteins in the hippocampal and cortical proteomes of 3- and 6-month-old mice. The plasma extracellular vesicle proteomes exhibited distinct informatic features compared with the other proteomes. Furthermore, the regulation of several canonical pathways (including phosphatidylinositol 3-kinase/protein kinase B signaling) differed between the hippocampus and cortex. Twelve potential biomarkers for the detection of early-stage Alzheimer's disease were identified and validated using plasma extracellular vesicles from stage-divided patients. Finally, integrin α-IIb, creatine kinase M-type, filamin C, glutamine γ-glutamyltransferase 2, and lysosomal α-mannosidase were selected as distinguishing biomarkers for healthy individuals and early-stage Alzheimer's disease patients using machine learning modeling with approximately 79% accuracy. Our study identified novel early-stage molecular signatures associated with the progression of Alzheimer's disease, thereby providing novel insights into its pathogenesis.

Development and Validation of a Visually Explainable Deep Learning Model for Classification of C-shaped Canals of the Mandibular Second Molars in Periapical and Panoramic Dental Radiographs.

INTRODUCTION: The purpose of this study was to develop and validate a visually explainable deep learning model for the classification of C-shaped canals of the mandibular second molars in dental radiographs. METHODS: The periapical and panoramic images of 1000 mandibular second molars were collected from 372 patients. The diagnostic performance of the deep learning system using periapical and panoramic radiographs was investigated in respect to its ability to determine whether the second mandibular molar showed a C-shaped canal configuration. The assessment of the canal configuration of cone-beam computed tomographic volumes from 372 patients (740 mandibular second molars) was used as a gold standard. RESULTS: The deep convolutional neural network algorithm model showed high accuracy in predicting the C-shaped canal variation among mandibular second molars in both periapical and panoramic images. The model demonstrated best results when using image patches including only the root portion of the tooth and when using both periapical and panoramic images for training (area under the curve [AUC] = 0.99). The model's diagnostic performance using only the root portion of the tooth (AUC: periapical = 0.98 and panoramic = 0.95) was similar to a specialist (AUC: periapical = 0.95 and panoramic = 0.96) and better than a novice general clinician (AUC: periapical = 0.89 and panoramic = 0.91). Both the specialist and general clinician showed better diagnostic performance when reading panoramic radiographs compared with periapical images. CONCLUSIONS: With further optimization of the test data using a larger data set and improvements made in the model, a deep learning system may be expected to effectively diagnose C-shaped canals and aid clinicians in practice and education.