Taeho Jo

Taeho Jo, Eun Hye Lee, Alzheimer's Disease Sequencing Project

INTRODUCTION: Alzheimer's disease (AD) is genetically complex, complicating robust classification from genomic data. METHODS: We developed a transformer-based ensemble model (TrUE-Net) using Monte Carlo Dropout for uncertainty estimation in AD classification from whole-genome sequencing (WGS). We combined a transformer that preserves single-nucleotide polymorphism (SNP) sequence structure with a concurrent random forest using flattened genotypes. An uncertainty threshold separated samples into an uncertain (high-variance) group and a more certain (low-variance) group. RESULTS: We analyzed 1050 individuals, holding out half for testing. Overall accuracy and area under the receiver operating characteristic (ROC) curve (AUC) were 0.6514 and 0.6636, respectively. Excluding the uncertain group improved accuracy from 0.6263 to 0.7287 (10.24% increase) and F1 from 0.5843 to 0.8205 (23.62% increase). DISCUSSION: Monte Carlo Dropout-driven uncertainty helps identify ambiguous cases that may require further clinical evaluation, thus improving reliability in AD genomic classification.

Taeho Jo, Kwangsik Nho, Andrew J. Saykin

Deep learning has shown outstanding performance in identifying intricate structures in complex high-dimensional data, especially in the domain of computer vision. The application of deep learning to early detection and automated classification of Alzheimer's disease (AD) has recently gained considerable attention, as rapid progress in neuroimaging techniques has generated large-scale multimodal neuroimaging data. A systematic review of publications using deep learning approaches and neuroimaging data for diagnostic classification of AD was performed. A PubMed and Google Scholar search was used to identify deep learning papers on AD published between January 2013 and July 2018. These papers were reviewed, evaluated, and classified by algorithm and neuroimaging type, and the findings were summarized. Of 16 studies meeting full inclusion criteria, 4 used a combination of deep learning and traditional machine learning approaches, and 12 used only deep learning approaches. The combination of traditional machine learning for classification and stacked auto-encoder (SAE) for feature selection produced accuracies of up to 98.8% for AD classification and 83.7% for prediction of conversion from mild cognitive impairment (MCI), a prodromal stage of AD, to AD. Deep learning approaches, such as convolutional neural network (CNN) or recurrent neural network (RNN), that use neuroimaging data without preprocessing for feature selection have yielded accuracies of up to 96.0% for AD classification and 84.2% for MCI conversion prediction. The best classification performance was obtained when multimodal neuroimaging and fluid biomarkers were combined. AD research that uses deep learning is still evolving, improving performance by incorporating additional hybrid data types, increasing transparency with explainable approaches that add knowledge of specific disease-related features and mechanisms.

Renzhi Cao, Taeho Jo, Jianlin Cheng

Protein structure prediction has been a grand challenge problem in the structure biology over the last few decades. Protein quality assessment plays a very important role in protein structure prediction. In the paper, we propose a new protein quality assessment method which can predict both local and global quality of the protein 3D structural models. Our method uses both multi and single model quality assessment method for global quality assessment, and uses chemical, physical, geo-metrical features, and global quality score for local quality assessment. CASP9 targets are used to generate the features for local quality assessment. We evaluate the performance of our local quality assessment method on CASP10, which is comparable with two stage-of-art QA methods based on the average absolute distance between the real and predicted distance. In addition, we blindly tested our method on CASP11, and the good performance shows that combining single and multiple model quality assessment method could be a good way to improve the accuracy of model quality assessment, and the random forest technique could be used to train a good local quality assessment model.