skip to main content

Title: Prioritizing Amyloid Imaging Biomarkers in Alzheimer’s Disease via Learning to Rank
We propose an innovative machine learning paradigm enabling precision medicine for AD biomarker discovery. The paradigm tailors the imaging biomarker discovery process to individual characteristics of a given patient. We implement this paradigm using a newly developed learning-to-rank method 𝙿𝙻𝚃𝚁 . The 𝙿𝙻𝚃𝚁 model seamlessly integrates two objectives for joint optimization: pushing up relevant biomarkers and ranking among relevant biomarkers. The empirical study of 𝙿𝙻𝚃𝚁 conducted on the ADNI data yields promising results to identify and prioritize individual-specific amyloid imaging biomarkers based on the individual’s structural MRI data. The resulting top ranked imaging biomarker has the potential to aid personalized diagnosis and disease subtyping.  more » « less
Award ID(s):
Author(s) / Creator(s):
; ; ; ; ;
Date Published:
Journal Name:
MBIA 2019: International Workshop on Multimodal Brain Image Analysis
LNCS 11846
Page Range / eLocation ID:
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. We propose an innovative machine learning paradigm enabling precision medicine for prioritizing cognitive assessments according to their relevance to Alzheimer's disease at the individual patient level. The paradigm tailors the cognitive biomarker discovery and cognitive assessment selection process to the brain morphometric characteristics of each individual patient. We implement this paradigm using a newly developed learning-to-rank method PLTR. Our empirical study on the ADNI data yields promising results to identify and prioritize individual-specific cognitive biomarkers as well as cognitive assessment tasks based on the individual's structural MRI data. The resulting top ranked cognitive biomarkers and assessment tasks have the potential to aid personalized diagnosis and disease subtyping. 
    more » « less
  2. Background: Type 1 diabetes (T1D) is a devastating disease with serious health complications. Early T1D biomarkers that could enable timely detection and prevention before the onset of clinical symptoms are paramount but currently unavailable. Despite their promise, omics approaches have so far failed to deliver such biomarkers, likely due to the fragmented nature of information obtained through the single omics approach. We recently demonstrated the utility of parallel multi-omics for the identification of T1D biomarker signatures. Our studies also identified challenges. Methods: Here, we evaluated a novel computational approach of data imputation and amplification as one way to overcome challenges associated with the relatively small number of subjects in these studies. Results: Using proprietary algorithms, we amplified our quadra-omics (proteomics, metabolomics, lipidomics, and transcriptomics) dataset from nine subjects a thousand-fold and analyzed the data using Ingenuity Pathway Analysis (IPA) software to assess the change in its analytical capabilities and biomarker prediction power in the amplified datasets compared to the original. These studies showed the ability to identify an increased number of T1D-relevant pathways and biomarkers in such computationally amplified datasets, especially, at imputation ratios close to the “golden ratio” of 38.2%:61.8%. Specifically, the Canonical Pathway and Diseases and Functions modules identified higher numbers of inflammatory pathways and functions relevant to autoimmune T1D, including novel ones not identified in the original data. The Biomarker Prediction module also predicted in the amplified data several unique biomarker candidates with direct links to T1D pathogenesis. Conclusions: These preliminary findings indicate that such large-scale data imputation and amplification approaches are useful in facilitating the discovery of candidate integrated biomarker signatures of T1D or other diseases by increasing the predictive range of existing data mining tools, especially when the size of the input data is inherently limited. 
    more » « less
  3. Alzheimer's Disease (AD) is a chronic neurodegenerative disease that severely impacts patients' thinking, memory and behavior. To aid automatic AD diagnoses, many longitudinal learning models have been proposed to predict clinical outcomes and/or disease status, which, though, often fail to consider missing temporal phenotypic records of the patients that can convey valuable information of AD progressions. Another challenge in AD studies is how to integrate heterogeneous genotypic and phenotypic biomarkers to improve diagnosis prediction. To cope with these challenges, in this paper we propose a longitudinal multi-modal method to learn enriched genotypic and phenotypic biomarker representations in the format of fixed-length vectors that can simultaneously capture the baseline neuroimaging measurements of the entire dataset and progressive variations of the varied counts of follow-up measurements over time of every participant from different biomarker sources. The learned global and local projections are aligned by a soft constraint and the structured-sparsity norm is used to uncover the multi-modal structure of heterogeneous biomarker measurements. While the proposed objective is clearly motivated to characterize the progressive information of AD developments, it is a nonsmooth objective that is difficult to efficiently optimize in general. Thus, we derive an efficient iterative algorithm, whose convergence is rigorously guaranteed in mathematics. We have conducted extensive experiments on the Alzheimer's Disease Neuroimaging Initiative (ADNI) data using one genotypic and two phenotypic biomarkers. Empirical results have demonstrated that the learned enriched biomarker representations are more effective in predicting the outcomes of various cognitive assessments. Moreover, our model has successfully identified disease-relevant biomarkers supported by existing medical findings that additionally warrant the correctness of our method from the clinical perspective. 
    more » « less
  4. Abstract

    With the explosive growth of biomarker data in Alzheimer’s disease (AD) clinical trials, numerous mathematical models have been developed to characterize disease-relevant biomarker trajectories over time. While some of these models are purely empiric, others are causal, built upon various hypotheses of AD pathophysiology, a complex and incompletely understood area of research. One of the most challenging problems in computational causal modeling is using a purely data-driven approach to derive the model’s parameters and the mathematical model itself, without any prior hypothesis bias. In this paper, we develop an innovative data-driven modeling approach to build and parameterize a causal model to characterize the trajectories of AD biomarkers. This approach integrates causal model learning, population parameterization, parameter sensitivity analysis, and personalized prediction. By applying this integrated approach to a large multicenter database of AD biomarkers, the Alzheimer’s Disease Neuroimaging Initiative, several causal models for different AD stages are revealed. In addition, personalized models for each subject are calibrated and provide accurate predictions of future cognitive status.

    more » « less
  5. Background Even before the onset of the COVID-19 pandemic, children and adolescents were experiencing a mental health crisis, partly due to a lack of quality mental health services. The rate of suicide for Black youth has increased by 80%. By 2025, the health care system will be short of 225,000 therapists, further exacerbating the current crisis. Therefore, it is of utmost importance for providers, schools, youth mental health, and pediatric medical providers to integrate innovation in digital mental health to identify problems proactively and rapidly for effective collaboration with other health care providers. Such approaches can help identify robust, reproducible, and generalizable predictors and digital biomarkers of treatment response in psychiatry. Among the multitude of digital innovations to identify a biomarker for psychiatric diseases currently, as part of the macrolevel digital health transformation, speech stands out as an attractive candidate with features such as affordability, noninvasive, and nonintrusive. Objective The protocol aims to develop speech-emotion recognition algorithms leveraging artificial intelligence/machine learning, which can establish a link between trauma, stress, and voice types, including disrupting speech-based characteristics, and detect clinically relevant emotional distress and functional impairments in children and adolescents. Methods Informed by theoretical foundations (the Theory of Psychological Trauma Biomarkers and Archetypal Voice Categories), we developed our methodology to focus on 5 emotions: anger, happiness, fear, neutral, and sadness. Participants will be recruited from 2 local mental health centers that serve urban youths. Speech samples, along with responses to the Symptom and Functioning Severity Scale, Patient Health Questionnaire 9, and Adverse Childhood Experiences scales, will be collected using an Android mobile app. Our model development pipeline is informed by Gaussian mixture model (GMM), recurrent neural network, and long short-term memory. Results We tested our model with a public data set. The GMM with 128 clusters showed an evenly distributed accuracy across all 5 emotions. Using utterance-level features, GMM achieved an accuracy of 79.15% overall, while frame selection increased accuracy to 85.35%. This demonstrates that GMM is a robust model for emotion classification of all 5 emotions and that emotion frame selection enhances accuracy, which is significant for scientific evaluation. Recruitment and data collection for the study were initiated in August 2021 and are currently underway. The study results are likely to be available and published in 2024. Conclusions This study contributes to the literature as it addresses the need for speech-focused digital health tools to detect clinically relevant emotional distress and functional impairments in children and adolescents. The preliminary results show that our algorithm has the potential to improve outcomes. The findings will contribute to the broader digital health transformation. International Registered Report Identifier (IRRID) DERR1-10.2196/46970 
    more » « less