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Description
No two cancers are alike. Cancer is a dynamic and heterogeneous disease, such heterogeneity arise among patients with the same cancer type, among cancer cells within the same individual’s tumor and even among cells within the same sub-clone over time. The recent application of next-generation sequencing and precision medicine techniques is the driving force to uncover the complexity of cancer and the best clinical practice. The core concept of precision medicine is to move away from crowd-based, best-for-most treatment and take individual variability into account when optimizing the prevention and treatment strategies. Next-generation sequencing is the method to sift through the entire 3 billion letters of each patient’s DNA genetic code in a massively parallel fashion.
The deluge of next-generation sequencing data nowadays has shifted the bottleneck of cancer research from multiple “-omics” data collection to integrative analysis and data interpretation. In this dissertation, I attempt to address two distinct, but dependent, challenges. The first is to design specific computational algorithms and tools that can process and extract useful information from the raw data in an efficient, robust, and reproducible manner. The second challenge is to develop high-level computational methods and data frameworks for integrating and interpreting these data. Specifically, Chapter 2 presents a tool called Snipea (SNv Integration, Prioritization, Ensemble, and Annotation) to further identify, prioritize and annotate somatic SNVs (Single Nucleotide Variant) called from multiple variant callers. Chapter 3 describes a novel alignment-based algorithm to accurately and losslessly classify sequencing reads from xenograft models. Chapter 4 describes a direct and biologically motivated framework and associated methods for identification of putative aberrations causing survival difference in GBM patients by integrating whole-genome sequencing, exome sequencing, RNA-Sequencing, methylation array and clinical data. Lastly, chapter 5 explores longitudinal and intratumor heterogeneity studies to reveal the temporal and spatial context of tumor evolution. The long-term goal is to help patients with cancer, particularly those who are in front of us today. Genome-based analysis of the patient tumor can identify genomic alterations unique to each patient’s tumor that are candidate therapeutic targets to decrease therapy resistance and improve clinical outcome.
The deluge of next-generation sequencing data nowadays has shifted the bottleneck of cancer research from multiple “-omics” data collection to integrative analysis and data interpretation. In this dissertation, I attempt to address two distinct, but dependent, challenges. The first is to design specific computational algorithms and tools that can process and extract useful information from the raw data in an efficient, robust, and reproducible manner. The second challenge is to develop high-level computational methods and data frameworks for integrating and interpreting these data. Specifically, Chapter 2 presents a tool called Snipea (SNv Integration, Prioritization, Ensemble, and Annotation) to further identify, prioritize and annotate somatic SNVs (Single Nucleotide Variant) called from multiple variant callers. Chapter 3 describes a novel alignment-based algorithm to accurately and losslessly classify sequencing reads from xenograft models. Chapter 4 describes a direct and biologically motivated framework and associated methods for identification of putative aberrations causing survival difference in GBM patients by integrating whole-genome sequencing, exome sequencing, RNA-Sequencing, methylation array and clinical data. Lastly, chapter 5 explores longitudinal and intratumor heterogeneity studies to reveal the temporal and spatial context of tumor evolution. The long-term goal is to help patients with cancer, particularly those who are in front of us today. Genome-based analysis of the patient tumor can identify genomic alterations unique to each patient’s tumor that are candidate therapeutic targets to decrease therapy resistance and improve clinical outcome.
ContributorsPeng, Sen (Author) / Dinu, Valentin (Thesis advisor) / Scotch, Matthew (Committee member) / Wallstrom, Garrick (Committee member) / Arizona State University (Publisher)
Created2015
Description
Text mining of biomedical literature and clinical notes is a very active field of research in biomedical science. Semantic analysis is one of the core modules for different Natural Language Processing (NLP) solutions. Methods for calculating semantic relatedness of two concepts can be very useful in solutions solving different problems such as relationship extraction, ontology creation and question / answering [1–6]. Several techniques exist in calculating semantic relatedness of two concepts. These techniques utilize different knowledge sources and corpora. So far, researchers attempted to find the best hybrid method for each domain by combining semantic relatedness techniques and data sources manually. In this work, attempts were made to eliminate the needs for manually combining semantic relatedness methods targeting any new contexts or resources through proposing an automated method, which attempted to find the best combination of semantic relatedness techniques and resources to achieve the best semantic relatedness score in every context. This may help the research community find the best hybrid method for each context considering the available algorithms and resources.
ContributorsEmadzadeh, Ehsan (Author) / Gonzalez, Graciela (Thesis advisor) / Greenes, Robert (Committee member) / Scotch, Matthew (Committee member) / Arizona State University (Publisher)
Created2016
Description
Accurate quantitative information of tumor/lesion volume plays a critical role
in diagnosis and treatment assessment. The current clinical practice emphasizes on efficiency, but sacrifices accuracy (bias and precision). In the other hand, many computational algorithms focus on improving the accuracy, but are often time consuming and cumbersome to use. Not to mention that most of them lack validation studies on real clinical data. All of these hinder the translation of these advanced methods from benchside to bedside.
In this dissertation, I present a user interactive image application to rapidly extract accurate quantitative information of abnormalities (tumor/lesion) from multi-spectral medical images, such as measuring brain tumor volume from MRI. This is enabled by a GPU level set method, an intelligent algorithm to learn image features from user inputs, and a simple and intuitive graphical user interface with 2D/3D visualization. In addition, a comprehensive workflow is presented to validate image quantitative methods for clinical studies.
This application has been evaluated and validated in multiple cases, including quantifying healthy brain white matter volume from MRI and brain lesion volume from CT or MRI. The evaluation studies show that this application has been able to achieve comparable results to the state-of-the-art computer algorithms. More importantly, the retrospective validation study on measuring intracerebral hemorrhage volume from CT scans demonstrates that not only the measurement attributes are superior to the current practice method in terms of bias and precision but also it is achieved without a significant delay in acquisition time. In other words, it could be useful to the clinical trials and clinical practice, especially when intervention and prognostication rely upon accurate baseline lesion volume or upon detecting change in serial lesion volumetric measurements. Obviously, this application is useful to biomedical research areas which desire an accurate quantitative information of anatomies from medical images. In addition, the morphological information is retained also. This is useful to researches which require an accurate delineation of anatomic structures, such as surgery simulation and planning.
in diagnosis and treatment assessment. The current clinical practice emphasizes on efficiency, but sacrifices accuracy (bias and precision). In the other hand, many computational algorithms focus on improving the accuracy, but are often time consuming and cumbersome to use. Not to mention that most of them lack validation studies on real clinical data. All of these hinder the translation of these advanced methods from benchside to bedside.
In this dissertation, I present a user interactive image application to rapidly extract accurate quantitative information of abnormalities (tumor/lesion) from multi-spectral medical images, such as measuring brain tumor volume from MRI. This is enabled by a GPU level set method, an intelligent algorithm to learn image features from user inputs, and a simple and intuitive graphical user interface with 2D/3D visualization. In addition, a comprehensive workflow is presented to validate image quantitative methods for clinical studies.
This application has been evaluated and validated in multiple cases, including quantifying healthy brain white matter volume from MRI and brain lesion volume from CT or MRI. The evaluation studies show that this application has been able to achieve comparable results to the state-of-the-art computer algorithms. More importantly, the retrospective validation study on measuring intracerebral hemorrhage volume from CT scans demonstrates that not only the measurement attributes are superior to the current practice method in terms of bias and precision but also it is achieved without a significant delay in acquisition time. In other words, it could be useful to the clinical trials and clinical practice, especially when intervention and prognostication rely upon accurate baseline lesion volume or upon detecting change in serial lesion volumetric measurements. Obviously, this application is useful to biomedical research areas which desire an accurate quantitative information of anatomies from medical images. In addition, the morphological information is retained also. This is useful to researches which require an accurate delineation of anatomic structures, such as surgery simulation and planning.
ContributorsXue, Wenzhe (Author) / Kaufman, David (Thesis advisor) / Mitchell, J. Ross (Thesis advisor) / Johnson, William (Committee member) / Scotch, Matthew (Committee member) / Arizona State University (Publisher)
Created2016
Description
Colorectal cancer is the second-highest cause of cancer-related deaths in the United States with approximately 50,000 estimated deaths in 2015. The advanced stages of colorectal cancer has a poor five-year survival rate of 10%, whereas the diagnosis in early stages of development has showed a more favorable five-year survival rate of 90%. Early diagnosis of colorectal cancer is achievable if colorectal polyps, a possible precursor to cancer, are detected and removed before developing into malignancy.
The preferred method for polyp detection and removal is optical colonoscopy. A colonoscopic procedure consists of two phases: (1) insertion phase during which a flexible endoscope (a flexible tube with a tiny video camera at the tip) is advanced via the anus and then gradually to the end of the colon--called the cecum, and (2) withdrawal phase during which the endoscope is gradually withdrawn while colonoscopists examine the colon wall to find and remove polyps. Colonoscopy is an effective procedure and has led to a significant decline in the incidence and mortality of colon cancer. However, despite many screening and therapeutic advantages, 1 out of every 4 polyps and 1 out of 13 colon cancers are missed during colonoscopy.
There are many factors that contribute to missed polyps and cancers including poor colon preparation, inadequate navigational skills, and fatigue. Poor colon preparation results in a substantial portion of colon covered with fecal content, hindering a careful examination of the colon. Inadequate navigational skills can prevent a colonoscopist from examining hard-to-reach regions of the colon that may contain a polyp. Fatigue can manifest itself in the performance of a colonoscopist by decreasing diligence and vigilance during procedures. Lack of vigilance may prevent a colonoscopist from detecting the polyps that briefly appear in the colonoscopy videos. Lack of diligence may result in hasty examination of the colon that is likely to miss polyps and lesions.
To reduce polyp and cancer miss rates, this research presents a quality assurance system with 3 components. The first component is an automatic polyp detection system that highlights the regions with suspected polyps in colonoscopy videos. The goal is to encourage more vigilance during procedures. The suggested polyp detection system consists of several novel modules: (1) a new patch descriptor that characterizes image appearance around boundaries more accurately and more efficiently than widely-used patch descriptors such HoG, LBP, and Daisy; (2) A 2-stage classification framework that is able to enhance low level image features prior to classification. Unlike the traditional way of image classification where a single patch undergoes the processing pipeline, our system fuses the information extracted from a pair of patches for more accurate edge classification; (3) a new vote accumulation scheme that robustly localizes objects with curvy boundaries in fragmented edge maps. Our voting scheme produces a probabilistic output for each polyp candidate but unlike the existing methods (e.g., Hough transform) does not require any predefined parametric model of the object of interest; (4) and a unique three-way image representation coupled with convolutional neural networks (CNNs) for classifying the polyp candidates. Our image representation efficiently captures a variety of features such as color, texture, shape, and temporal information and significantly improves the performance of the subsequent CNNs for candidate classification. This contrasts with the exiting methods that mainly rely on a subset of the above image features for polyp detection. Furthermore, this research is the first to investigate the use of CNNs for polyp detection in colonoscopy videos.
The second component of our quality assurance system is an automatic image quality assessment for colonoscopy. The goal is to encourage more diligence during procedures by warning against hasty and low quality colon examination. We detect a low quality colon examination by identifying a number of consecutive non-informative frames in videos. We base our methodology for detecting non-informative frames on two key observations: (1) non-informative frames
most often show an unrecognizable scene with few details and blurry edges and thus their information can be locally compressed in a few Discrete Cosine Transform (DCT) coefficients; however, informative images include much more details and their information content cannot be summarized by a small subset of DCT coefficients; (2) information content is spread all over the image in the case of informative frames, whereas in non-informative frames, depending on image artifacts and degradation factors, details may appear in only a few regions. We use the former observation in designing our global features and the latter in designing our local image features. We demonstrated that the suggested new features are superior to the existing features based on wavelet and Fourier transforms.
The third component of our quality assurance system is a 3D visualization system. The goal is to provide colonoscopists with feedback about the regions of the colon that have remained unexamined during colonoscopy, thereby helping them improve their navigational skills. The suggested system is based on a new 3D reconstruction algorithm that combines depth and position information for 3D reconstruction. We propose to use a depth camera and a tracking sensor to obtain depth and position information. Our system contrasts with the existing works where the depth and position information are unreliably estimated from the colonoscopy frames. We conducted a use case experiment, demonstrating that the suggested 3D visualization system can determine the unseen regions of the navigated environment. However, due to technology limitations, we were not able to evaluate our 3D visualization system using a phantom model of the colon.
The preferred method for polyp detection and removal is optical colonoscopy. A colonoscopic procedure consists of two phases: (1) insertion phase during which a flexible endoscope (a flexible tube with a tiny video camera at the tip) is advanced via the anus and then gradually to the end of the colon--called the cecum, and (2) withdrawal phase during which the endoscope is gradually withdrawn while colonoscopists examine the colon wall to find and remove polyps. Colonoscopy is an effective procedure and has led to a significant decline in the incidence and mortality of colon cancer. However, despite many screening and therapeutic advantages, 1 out of every 4 polyps and 1 out of 13 colon cancers are missed during colonoscopy.
There are many factors that contribute to missed polyps and cancers including poor colon preparation, inadequate navigational skills, and fatigue. Poor colon preparation results in a substantial portion of colon covered with fecal content, hindering a careful examination of the colon. Inadequate navigational skills can prevent a colonoscopist from examining hard-to-reach regions of the colon that may contain a polyp. Fatigue can manifest itself in the performance of a colonoscopist by decreasing diligence and vigilance during procedures. Lack of vigilance may prevent a colonoscopist from detecting the polyps that briefly appear in the colonoscopy videos. Lack of diligence may result in hasty examination of the colon that is likely to miss polyps and lesions.
To reduce polyp and cancer miss rates, this research presents a quality assurance system with 3 components. The first component is an automatic polyp detection system that highlights the regions with suspected polyps in colonoscopy videos. The goal is to encourage more vigilance during procedures. The suggested polyp detection system consists of several novel modules: (1) a new patch descriptor that characterizes image appearance around boundaries more accurately and more efficiently than widely-used patch descriptors such HoG, LBP, and Daisy; (2) A 2-stage classification framework that is able to enhance low level image features prior to classification. Unlike the traditional way of image classification where a single patch undergoes the processing pipeline, our system fuses the information extracted from a pair of patches for more accurate edge classification; (3) a new vote accumulation scheme that robustly localizes objects with curvy boundaries in fragmented edge maps. Our voting scheme produces a probabilistic output for each polyp candidate but unlike the existing methods (e.g., Hough transform) does not require any predefined parametric model of the object of interest; (4) and a unique three-way image representation coupled with convolutional neural networks (CNNs) for classifying the polyp candidates. Our image representation efficiently captures a variety of features such as color, texture, shape, and temporal information and significantly improves the performance of the subsequent CNNs for candidate classification. This contrasts with the exiting methods that mainly rely on a subset of the above image features for polyp detection. Furthermore, this research is the first to investigate the use of CNNs for polyp detection in colonoscopy videos.
The second component of our quality assurance system is an automatic image quality assessment for colonoscopy. The goal is to encourage more diligence during procedures by warning against hasty and low quality colon examination. We detect a low quality colon examination by identifying a number of consecutive non-informative frames in videos. We base our methodology for detecting non-informative frames on two key observations: (1) non-informative frames
most often show an unrecognizable scene with few details and blurry edges and thus their information can be locally compressed in a few Discrete Cosine Transform (DCT) coefficients; however, informative images include much more details and their information content cannot be summarized by a small subset of DCT coefficients; (2) information content is spread all over the image in the case of informative frames, whereas in non-informative frames, depending on image artifacts and degradation factors, details may appear in only a few regions. We use the former observation in designing our global features and the latter in designing our local image features. We demonstrated that the suggested new features are superior to the existing features based on wavelet and Fourier transforms.
The third component of our quality assurance system is a 3D visualization system. The goal is to provide colonoscopists with feedback about the regions of the colon that have remained unexamined during colonoscopy, thereby helping them improve their navigational skills. The suggested system is based on a new 3D reconstruction algorithm that combines depth and position information for 3D reconstruction. We propose to use a depth camera and a tracking sensor to obtain depth and position information. Our system contrasts with the existing works where the depth and position information are unreliably estimated from the colonoscopy frames. We conducted a use case experiment, demonstrating that the suggested 3D visualization system can determine the unseen regions of the navigated environment. However, due to technology limitations, we were not able to evaluate our 3D visualization system using a phantom model of the colon.
ContributorsTajbakhsh, Nima (Author) / Liang, Jianming (Thesis advisor) / Greenes, Robert (Committee member) / Scotch, Matthew (Committee member) / Arizona State University (Publisher)
Created2015
Description
Unstructured texts containing biomedical information from sources such as electronic health records, scientific literature, discussion forums, and social media offer an opportunity to extract information for a wide range of applications in biomedical informatics. Building scalable and efficient pipelines for natural language processing and extraction of biomedical information plays an important role in the implementation and adoption of applications in areas such as public health. Advancements in machine learning and deep learning techniques have enabled rapid development of such pipelines. This dissertation presents entity extraction pipelines for two public health applications: virus phylogeography and pharmacovigilance. For virus phylogeography, geographical locations are extracted from biomedical scientific texts for metadata enrichment in the GenBank database containing 2.9 million virus nucleotide sequences. For pharmacovigilance, tools are developed to extract adverse drug reactions from social media posts to open avenues for post-market drug surveillance from non-traditional sources. Across these pipelines, high variance is observed in extraction performance among the entities of interest while using state-of-the-art neural network architectures. To explain the variation, linguistic measures are proposed to serve as indicators for entity extraction performance and to provide deeper insight into the domain complexity and the challenges associated with entity extraction. For both the phylogeography and pharmacovigilance pipelines presented in this work the annotated datasets and applications are open source and freely available to the public to foster further research in public health.
ContributorsMagge, Arjun (Author) / Scotch, Matthew (Thesis advisor) / Gonzalez-Hernandez, Graciela (Thesis advisor) / Greenes, Robert (Committee member) / Arizona State University (Publisher)
Created2019