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Abstract BackgroundAlzheimer’s Disease (AD) is a widespread neurodegenerative disease with Mild Cognitive Impairment (MCI) acting as an interim phase between normal cognitive state and AD. The irreversible nature of AD and the difficulty in early prediction present significant challenges for patients, caregivers, and the healthcare sector. Deep learning (DL) methods such as Recurrent Neural Networks (RNN) have been utilized to analyze Electronic Health Records (EHR) to model disease progression and predict diagnosis. However, these models do not address some inherent irregularities in EHR data such as irregular time intervals between clinical visits. Furthermore, most DL models are not interpretable. To address these issues, we developed a novel DL architecture called Time‐Aware RNN (TA‐RNN) to predict MCI to AD conversion at the next clinical visit. MethodTA‐RNN comprises of a time embedding layer, attention‐based RNN, and prediction layer based on multi‐layer perceptron (MLP) (Figure 1). For interpretability, a dual‐level attention mechanism within the RNN identifies significant visits and features impacting predictions. TA‐RNN addresses irregular time intervals by incorporating time embedding into longitudinal cognitive and neuroimaging data based on attention weights to create a patient embedding. The MLP, trained on demographic data and the patient embedding predicts AD conversion. TA‐RNN was evaluated on Alzheimer’s Disease Neuroimaging Initiative (ADNI) and National Alzheimer’s Coordinating Center (NACC) datasets based on F2 score and sensitivity. ResultMultiple TA‐RNN models were trained with two, three, five, or six visits to predict the diagnosis at the next visit. In one setup, the models were trained and tested on ADNI. In another setup, the models were trained on the entire ADNI dataset and evaluated on the entire NACC dataset. The results indicated superior performance of TA‐RNN compared to state‐of‐the‐art (SOTA) and baseline approaches for both setups (Figure 2A and 2B). Based on attention weights, we also highlighted significant visits (Figure 3A) and features (Figure 3B) and observed that CDRSB and FAQ features and the most recent visit had highest influence in predictions. ConclusionWe propose TA‐RNN, an interpretable model to predict MCI to AD conversion while handling irregular time intervals. TA‐RNN outperformed SOTA and baseline methods in multiple experiments. 

Abstract Clinical diagnosis of Alzheimer’s disease (AD) is usually made after symptoms such as short-term memory loss are exhibited, which minimizes the intervention and treatment options. The existing screening techniques cannot distinguish between stable MCI (sMCI) cases (i.e., patients who do not convert to AD for at least three years) and progressive MCI (pMCI) cases (i.e., patients who convert to AD in three years or sooner). Delayed diagnosis of AD also disproportionately affects underrepresented and socioeconomically disadvantaged populations. The significant positive impact of an early diagnosis solution for AD across diverse ethno-racial and demographic groups is well-known and recognized. While advancements in high-throughput technologies have enabled the generation of vast amounts of multimodal clinical, and neuroimaging datasets related to AD, most methods utilizing these data sets for diagnostic purposes have not found their way in clinical settings. To better understand the landscape, we surveyed the major preprocessing, data management, traditional machine-learning (ML), and deep learning (DL) techniques used for diagnosing AD using neuroimaging data such as structural magnetic resonance imaging (sMRI), functional magnetic resonance imaging (fMRI), and positron emission tomography (PET). Once we had a good understanding of the methods available, we conducted a study to assess the reproducibility and generalizability of open-source ML models. Our evaluation shows that existing models show reduced generalizability when different cohorts of the data modality are used while controlling other computational factors. The paper concludes with a discussion of major challenges that plague ML models for AD diagnosis and biomarker discovery. 

Abstract Database peptide search is the primary computational technique for identifying peptides from the mass spectrometry (MS) data. Graphical Processing Units (GPU) computing is now ubiquitous in the current-generation of high-performance computing (HPC) systems, yet its application in the database peptide search domain remains limited. Part of the reason is the use of sub-optimal algorithms in the existing GPU-accelerated methods resulting in significantly inefficient hardware utilization. In this paper, we design and implement a new-age CPU-GPU HPC framework, calledGiCOPS, for efficient and complete GPU-acceleration of the modern database peptide search algorithms on supercomputers. Our experimentation shows that the GiCOPS exhibits between 1.2 to 5$$\times$$ $\times$speed improvement over its CPU-only predecessor, HiCOPS, and over 10$$\times$$ $\times$improvement over several existing GPU-based database search algorithms for sufficiently large experiment sizes. We further assess and optimize the performance of our framework using the Roofline Model and report near-optimal results for several metrics including computations per second, occupancy rate, memory workload, branch efficiency and shared memory performance. Finally, the CPU-GPU methods and optimizations proposed in our work for complex integer- and memory-bounded algorithmic pipelines can also be extended to accelerate the existing and future peptide identification algorithms. GiCOPS is now integrated with our umbrella HPC framework HiCOPS and is available at:https://github.com/pcdslab/gicops.