Unsupervised learning of time series data, also known as temporal clustering, is a challenging problem in machine learning. This thesis presents a novel algorithm, Deep Temporal Clustering (DTC), to naturally integrate dimensionality reduction and temporal clustering into a single end-to-end…
Unsupervised learning of time series data, also known as temporal clustering, is a challenging problem in machine learning. This thesis presents a novel algorithm, Deep Temporal Clustering (DTC), to naturally integrate dimensionality reduction and temporal clustering into a single end-to-end learning framework, fully unsupervised. The algorithm utilizes an autoencoder for temporal dimensionality reduction and a novel temporal clustering layer for cluster assignment. Then it jointly optimizes the clustering objective and the dimensionality reduction objective. Based on requirement and application, the temporal clustering layer can be customized with any temporal similarity metric. Several similarity metrics and state-of-the-art algorithms are considered and compared. To gain insight into temporal features that the network has learned for its clustering, a visualization method is applied that generates a region of interest heatmap for the time series. The viability of the algorithm is demonstrated using time series data from diverse domains, ranging from earthquakes to spacecraft sensor data. In each case, the proposed algorithm outperforms traditional methods. The superior performance is attributed to the fully integrated temporal dimensionality reduction and clustering criterion.
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While techniques for reading DNA in some capacity has been possible for decades,
the ability to accurately edit genomes at scale has remained elusive. Novel techniques
have been introduced recently to aid in the writing of DNA sequences. While writing
DNA is more…
While techniques for reading DNA in some capacity has been possible for decades,
the ability to accurately edit genomes at scale has remained elusive. Novel techniques
have been introduced recently to aid in the writing of DNA sequences. While writing
DNA is more accessible, it still remains expensive, justifying the increased interest in
in silico predictions of cell behavior. In order to accurately predict the behavior of
cells it is necessary to extensively model the cell environment, including gene-to-gene
interactions as completely as possible.
Significant algorithmic advances have been made for identifying these interactions,
but despite these improvements current techniques fail to infer some edges, and
fail to capture some complexities in the network. Much of this limitation is due to
heavily underdetermined problems, whereby tens of thousands of variables are to be
inferred using datasets with the power to resolve only a small fraction of the variables.
Additionally, failure to correctly resolve gene isoforms using short reads contributes
significantly to noise in gene quantification measures.
This dissertation introduces novel mathematical models, machine learning techniques,
and biological techniques to solve the problems described above. Mathematical
models are proposed for simulation of gene network motifs, and raw read simulation.
Machine learning techniques are shown for DNA sequence matching, and DNA
sequence correction.
Results provide novel insights into the low level functionality of gene networks. Also
shown is the ability to use normalization techniques to aggregate data for gene network
inference leading to larger data sets while minimizing increases in inter-experimental
noise. Results also demonstrate that high error rates experienced by third generation
sequencing are significantly different than previous error profiles, and that these errors can be modeled, simulated, and rectified. Finally, techniques are provided for amending this DNA error that preserve the benefits of third generation sequencing.
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Open source image analytics and data mining software are widely available but can be overly-complicated and non-intuitive for medical physicians and researchers to use. The ASU-Mayo Clinic Imaging Informatics Lab has developed an in-house pipeline to process medical images, extract…
Open source image analytics and data mining software are widely available but can be overly-complicated and non-intuitive for medical physicians and researchers to use. The ASU-Mayo Clinic Imaging Informatics Lab has developed an in-house pipeline to process medical images, extract imaging features, and develop multi-parametric models to assist disease staging and diagnosis. The tools have been extensively used in a number of medical studies including brain tumor, breast cancer, liver cancer, Alzheimer's disease, and migraine. Recognizing the need from users in the medical field for a simplified interface and streamlined functionalities, this project aims to democratize this pipeline so that it is more readily available to health practitioners and third party developers.
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Alzheimer’s disease (AD) involves a gradual breakdown of brain connectivity, and network analyses offer a promising new approach to track and understand disease progression. Even so, our ability to detect degenerative changes in brain networks depends on the methods used.…
Alzheimer’s disease (AD) involves a gradual breakdown of brain connectivity, and network analyses offer a promising new approach to track and understand disease progression. Even so, our ability to detect degenerative changes in brain networks depends on the methods used. Here we compared several tractography and feature extraction methods to see which ones gave best diagnostic classification for 202 people with AD, mild cognitive impairment or normal cognition, scanned with 41-gradient diffusion-weighted magnetic resonance imaging as part of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) project. We computed brain networks based on whole brain tractography with nine different methods – four of them tensor-based deterministic (FACT, RK2, SL, and TL), two orientation distribution function (ODF)-based deterministic (FACT, RK2), two ODF-based probabilistic approaches (Hough and PICo), and one “ball-and-stick” approach (Probtrackx). Brain networks derived from different tractography algorithms did not differ in terms of classification performance on ADNI, but performing principal components analysis on networks helped classification in some cases. Small differences may still be detectable in a truly vast cohort, but these experiments help assess the relative advantages of different tractography algorithms, and different post-processing choices, when used for classification.
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Alzheimer's disease (AD) is a progressive brain disease. Accurate detection of AD and its prodromal stage, mild cognitive impairment (MCI), are crucial. There is also a growing interest in identifying brain imaging biomarkers that help to automatically differentiate stages of…
Alzheimer's disease (AD) is a progressive brain disease. Accurate detection of AD and its prodromal stage, mild cognitive impairment (MCI), are crucial. There is also a growing interest in identifying brain imaging biomarkers that help to automatically differentiate stages of Alzheimer's disease. Here, we focused on brain structural networks computed from diffusion MRI and proposed a new feature extraction and classification framework based on higher order singular value decomposition and sparse logistic regression. In tests on publicly available data from the Alzheimer's Disease Neuroimaging Initiative, our proposed framework showed promise in detecting brain network differences that help in classifying different stages of Alzheimer's disease.
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Understanding the extent to which vascular disease and its risk factors are associated with prodromal dementia, notably Alzheimer's disease (AD), may enhance predictive accuracy as well as guide early interventions. One promising avenue to determine this relationship consists of looking…
Understanding the extent to which vascular disease and its risk factors are associated with prodromal dementia, notably Alzheimer's disease (AD), may enhance predictive accuracy as well as guide early interventions. One promising avenue to determine this relationship consists of looking for reliable and sensitive in-vivo imaging methods capable of characterizing the subtle brain alterations before the clinical manifestations. However, little is known from the imaging perspective about how risk factors such as vascular disease influence AD progression. Here, for the first time, we apply an innovative T1 and DTI fusion analysis of 3D corpus callosum (CC) on mild cognitive impairment (MCI) populations with different levels of vascular profile, aiming to de-couple the vascular factor in the prodromal AD stage. Our new fusion method successfully increases the detection power for differentiating MCI subjects with high from low vascular risk profiles, as well as from healthy controls. MCI subjects with high and low vascular risk profiles showed differed alteration patterns in the anterior CC, which may help to elucidate the inter-wired relationship between MCI and vascular risk factors.
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Recent neuroimaging findings have highlighted the impact of premature birth on subcortical development and morphological changes in the deep grey nuclei and ventricular system. To help characterize subcortical microstructural changes in preterm neonates, we recently implemented a multivariate tensor-based method…
Recent neuroimaging findings have highlighted the impact of premature birth on subcortical development and morphological changes in the deep grey nuclei and ventricular system. To help characterize subcortical microstructural changes in preterm neonates, we recently implemented a multivariate tensor-based method (mTBM). This method allows to precisely measure local surface deformation of brain structures in infants. Here, we investigated ventricular abnormalities and their spatial relationships with surrounding subcortical structures in preterm neonates. We performed regional group comparisons on the surface morphometry and relative position of the lateral ventricles between 19 full-term and 17 preterm born neonates at term-equivalent age. Furthermore, a relative pose analysis was used to detect individual differences in translation, rotation, and scale of a given brain structure with respect to an average. Our mTBM results revealed broad areas of alterations on the frontal horn and body of the left ventricle, and narrower areas of differences on the temporal horn of the right ventricle. A significant shift in the rotation of the left ventricle was also found in preterm neonates. Furthermore, we located significant correlations between morphology and pose parameters of the lateral ventricles and that of the putamen and thalamus. These results show that regional abnormalities on the surface and pose of the ventricles are also associated with alterations on the putamen and thalamus. The complementarity of the information provided by the surface and pose analysis may help to identify abnormal white and grey matter growth, hinting toward a pattern of neural and cellular dysmaturation.
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Chronic manganese (Mn) exposure is associated with neuromotor and neurocognitive deficits, but the exact mechanism of Mn neurotoxicity is still unclear. With the advent of magnetic resonance imaging (MRI), in-vivo analysis of brain structures has become possible. Among different sub-cortical…
Chronic manganese (Mn) exposure is associated with neuromotor and neurocognitive deficits, but the exact mechanism of Mn neurotoxicity is still unclear. With the advent of magnetic resonance imaging (MRI), in-vivo analysis of brain structures has become possible. Among different sub-cortical structures, the basal ganglia (BG) has been investigated as a putative anatomical biomarker in MR-based studies of Mn toxicity. However, previous investigations have yielded inconsistent results in terms of regional MR signal intensity changes. These discrepancies may be due to the subtlety of brain alterations caused by Mn toxicity, coupled to analysis techniques that lack the requisite detection power. Here, based on brain MRI, we apply a 3D surface-based morphometry method on 3 bilateral basal ganglia structures in school-age children chronically exposed to Mn through drinking water to investigate the effect of Mn exposure on brain anatomy. Our method successfully pinpointed significant enlargement of many areas of the basal ganglia structures, preferentially affecting the putamen. Moreover, these areas showed significant correlations with fine motor performance, indicating a possible link between altered basal ganglia neurodevelopment and declined motor performance in high Mn exposed children.
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Alzheimer’s disease (AD), is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. It is the cause of 60% to 70% of cases of dementia. There is growing interest in identifying brain image biomarkers that hel…
Alzheimer’s disease (AD), is a chronic neurodegenerative disease that usually starts slowly and gets worse over time. It is the cause of 60% to 70% of cases of dementia. There is growing interest in identifying brain image biomarkers that help evaluate AD risk pre-symptomatically. High-dimensional non-linear pattern classification methods have been applied to structural magnetic resonance images (MRI’s) and used to discriminate between clinical groups in Alzheimers progression. Using Fluorodeoxyglucose (FDG) positron emission tomography (PET) as the pre- ferred imaging modality, this thesis develops two independent machine learning based patch analysis methods and uses them to perform six binary classification experiments across different (AD) diagnostic categories. Specifically, features were extracted and learned using dimensionality reduction and dictionary learning & sparse coding by taking overlapping patches in and around the cerebral cortex and using them as fea- tures. Using AdaBoost as the preferred choice of classifier both methods try to utilize 18F-FDG PET as a biological marker in the early diagnosis of Alzheimer’s . Addi- tional we investigate the involvement of rich demographic features (ApoeE3, ApoeE4 and Functional Activities Questionnaires (FAQ)) in classification. The experimental results on Alzheimer’s Disease Neuroimaging initiative (ADNI) dataset demonstrate the effectiveness of both the proposed systems. The use of 18F-FDG PET may offer a new sensitive biomarker and enrich the brain imaging analysis toolset for studying the diagnosis and prognosis of AD.
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Alzheimer’s Disease (AD), a neurodegenerative disease is a progressive disease that affects the brain gradually with time and worsens. Reliable and early diagnosis of AD and its prodromal stages (i.e. Mild Cognitive Impairment(MCI)) is essential. Fluorodeoxyglucose (FDG) positron emission tomography…
Alzheimer’s Disease (AD), a neurodegenerative disease is a progressive disease that affects the brain gradually with time and worsens. Reliable and early diagnosis of AD and its prodromal stages (i.e. Mild Cognitive Impairment(MCI)) is essential. Fluorodeoxyglucose (FDG) positron emission tomography (PET) measures the decline in the regional cerebral metabolic rate for glucose, offering a reliable metabolic biomarker even on presymptomatic AD patients. PET scans provide functional information that is unique and unavailable using other types of imaging. The computational efficacy of FDG-PET data alone, for the classification of various Alzheimer’s Diagnostic categories (AD, MCI (LMCI, EMCI), Control) has not been studied. This serves as motivation to correctly classify the various diagnostic categories using FDG-PET data. Deep learning has recently been applied to the analysis of structural and functional brain imaging data. This thesis is an introduction to a deep learning based classification technique using neural networks with dimensionality reduction techniques to classify the different stages of AD based on FDG-PET image analysis.
This thesis develops a classification method to investigate the performance of FDG-PET as an effective biomarker for Alzheimer's clinical group classification. This involves dimensionality reduction using Probabilistic Principal Component Analysis on max-pooled data and mean-pooled data, followed by a Multilayer Feed Forward Neural Network which performs binary classification. Max pooled features result into better classification performance compared to results on mean pooled features. Additionally, experiments are done to investigate if the addition of important demographic features such as Functional Activities Questionnaire(FAQ), gene information helps improve performance. Classification results indicate that our designed classifiers achieve competitive results, and better with the additional of demographic features.
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