DNA methylation-based classification of central nervous system tumours.

Accurate pathological diagnosis is crucial for optimal management of patients with cancer. For the approximately 100 known tumour types of the central nervous system, standardization of the diagnostic process has been shown to be particularly challenging-with substantial inter-observer variability in the histopathological diagnosis of many tumour types. Here we present a comprehensive approach for the DNA methylation-based classification of central nervous system tumours across all entities and age groups, and demonstrate its application in a routine diagnostic setting. We show that the availability of this method may have a substantial impact on diagnostic precision compared to standard methods, resulting in a change of diagnosis in up to 12% of prospective cases. For broader accessibility, we have designed a free online classifier tool, the use of which does not require any additional onsite data processing. Our results provide a blueprint for the generation of machine-learning-based tumour classifiers across other cancer entities, with the potential to fundamentally transform tumour pathology

Washington University Record, April 8, 2005

https://digitalcommons.wustl.edu/record/2033/thumbnail.jp

Hydra: A mixture modeling framework for subtyping pediatric cancer cohorts using multimodal gene expression signatures.

Precision oncology has primarily relied on coding mutations as biomarkers of response to therapies. While transcriptome analysis can provide valuable information, incorporation into workflows has been difficult. For example, the relative rather than absolute gene expression level needs to be considered, requiring differential expression analysis across samples. However, expression programs related to the cell-of-origin and tumor microenvironment effects confound the search for cancer-specific expression changes. To address these challenges, we developed an unsupervised clustering approach for discovering differential pathway expression within cancer cohorts using gene expression measurements. The hydra approach uses a Dirichlet process mixture model to automatically detect multimodally distributed genes and expression signatures without the need for matched normal tissue. We demonstrate that the hydra approach is more sensitive than widely-used gene set enrichment approaches for detecting multimodal expression signatures. Application of the hydra analysis framework to small blue round cell tumors (including rhabdomyosarcoma, synovial sarcoma, neuroblastoma, Ewing sarcoma, and osteosarcoma) identified expression signatures associated with changes in the tumor microenvironment. The hydra approach also identified an association between ATRX deletions and elevated immune marker expression in high-risk neuroblastoma. Notably, hydra analysis of all small blue round cell tumors revealed similar subtypes, characterized by changes to infiltrating immune and stromal expression signatures

Fusion, 2009

https://hsrc.himmelfarb.gwu.edu/smhs_fusion/1002/thumbnail.jp

Poster Presentations from the 2018 Maine Medical Center Research Institute (MMCRI) Summer Student Research Program

The following posters were presented as part of the 2018 MMCRI Summer Student Research Program. This program offers undergraduates and medical students a unique opportunity to conduct research in diverse clinical and biomedical science fields during the summer months. During the paid ten-week program, students participate in mentored independent research projects either in our state-of-the-art research facility, or working with physicians in a hospital setting to impact patient care or the outcome of treatment. Students also attend lectures and workshops featuring topics including bioethics, animal use in biomedical science and scientific presentation skills, and have the opportunity to attend presentations by guest scientists and MMCRI faculty. All students give a final presentation, which in 2018 involved a three minute oral presentation called a “Three Minute Thesis” as well as a scientific poster presentation. All authors have an affiliation with MMCRI, unless otherwise noted

Mathematics in Medical Diagnostics - 2022 Proceedings of the 4th International Conference on Trauma Surgery Technology

The 4th event of the Giessen International Conference Series on Trauma Surgery Technology took place on April, the 23rd 2022 in Warsaw, Poland. It aims to bring together practical application research, with a focus on medical imaging, and the TDA experts from Warsaw. This publication contains details of our presentations and discussions

Emotion Regulation Flexibility and Electronic Patient-Reported Outcomes : A Framework for Understanding Symptoms and Affect Dynamics in Pediatric Psycho-Oncology

Emotion dysregulation is regarded as a driving mechanism for the development of mental health problems and psychopathology. The role of emotion regulation (ER) in the management of cancer distress and quality of life (QoL) has recently been recognized in psycho-oncology. The latest technological advances afford ways to assess ER, affective experiences and QoL in child, adolescent and young adult (CAYA) cancer patients through electronic patient-reported outcomes (ePRO) in their daily environment in real-time. Such tools facilitate ways to study the dynamics of affect and the flexibility of ER. However, technological advancement is not risk-free. We critically review the literature on ePRO in cancer existing models of ER in pediatric psycho-oncology and analyze strength, weaknesses, opportunities and threats of ePRO with a focus on CAYA cancer research and care. Supported by personal study-based experiences, this narrative review serves as a foundation to propose a novel methodological and metatheoretical framework based on: (a) an extended notion of ER, which includes its dynamic, adaptive and flexible nature and focuses on processes and conditions rather than fixed categorical strategies; (b) ePRO as a means to measure emotion regulation flexibility and affect dynamics; (c) identifying early warning signals for symptom change via ePRO and building forecasting models using dynamical systems theory

Tools for Large-scale Genomic Analysis and Gene Expression Outlier Modeling for Precision Therapeutics

In terms of data acquisition, storage, and distribution, genomics data will soon become the largest “big data” domain in science and, as such, needs appropriate tools to process the ever-increasing amount of genomic data so researchers can leverage the power afforded by such enormous datasets. I present my work on Toil: a portable, open-source workflow software that supports contemporary workflow definition languages and can securely and reproducibly run scientific workflows efficiently at large-scale. Yet efficient computation is only one component of enabling scientific research, as data is not always accessible to researchers who can use it. Data barriers hinder scientific progress and stymie research collaboration by denying access to large amounts of biomedical information, due to the need for patient privacy and potential liability on behalf of data stewards. As such, research institutions and consortiums should prioritize making large datasets open-access to enable research teams to develop novel therapeutics and garner valuable insight into a wide variety of diseases. One such research group who benefits from both large open-access datasets is Treehouse, a pediatric cancer research group that investigates the role of RNA-seq in therapeutics. However, Treehouse also needs methods to extract rare pediatric cancer data from information silos. Treehouse uses RNA-seq to identify target drug candidates by comparing gene expression for individual patients to their own public compendium, which combines multiple open-access datasets with thousands of pediatric samples. I discuss a solution for extracting data from information silos by using portable and reproducible software that produces anonymized secondary output that can be sent back to the researcher for analysis. This computation-to-data method also addresses the logistical difficulty of securely sharing and storing large amounts of primary sequence data. Finally, I propose a robust Bayesian statistical framework for detecting gene expression outliers in single samples that leverages all available data to produce a consensus background distribution for each gene of interest without requiring the researcher to manually select a comparison set and provides posterior predictive p-values to quantify over- or under-expression

Using machine learning to support better and intelligent visualisation for genomic data

Massive amounts of genomic data are created for the advent of Next Generation Sequencing technologies. Great technological advances in methods of characterising the human diseases, including genetic and environmental factors, make it a great opportunity to understand the diseases and to find new diagnoses and treatments. Translating medical data becomes more and more rich and challenging. Visualisation can greatly aid the processing and integration of complex data. Genomic data visual analytics is rapidly evolving alongside with advances in high-throughput technologies such as Artificial Intelligence (AI), and Virtual Reality (VR). Personalised medicine requires new genomic visualisation tools, which can efficiently extract knowledge from the genomic data effectively and speed up expert decisions about the best treatment of an individual patient’s needs. However, meaningful visual analysis of such large genomic data remains a serious challenge. Visualising these complex genomic data requires not only simply plotting of data but should also lead to better decisions. Machine learning has the ability to make prediction and aid in decision-making. Machine learning and visualisation are both effective ways to deal with big data, but they focus on different purposes. Machine learning applies statistical learning techniques to automatically identify patterns in data to make highly accurate prediction, while visualisation can leverage the human perceptual system to interpret and uncover hidden patterns in big data. Clinicians, experts and researchers intend to use both visualisation and machine learning to analyse their complex genomic data, but it is a serious challenge for them to understand and trust machine learning models in the serious medical industry. The main goal of this thesis is to study the feasibility of intelligent and interactive visualisation which combined with machine learning algorithms for medical data analysis. A prototype has also been developed to illustrate the concept that visualising genomics data from childhood cancers in meaningful and dynamic ways could lead to better decisions. Machine learning algorithms are used and illustrated during visualising the cancer genomic data in order to provide highly accurate predictions. This research could open a new and exciting path to discovery for disease diagnostics and therapies

A study assessing the characteristics of big data environments that predict high research impact: application of qualitative and quantitative methods

BACKGROUND: Big data offers new opportunities to enhance healthcare practice. While researchers have shown increasing interest to use them, little is known about what drives research impact. We explored predictors of research impact, across three major sources of healthcare big data derived from the government and the private sector. METHODS: This study was based on a mixed methods approach. Using quantitative analysis, we first clustered peer-reviewed original research that used data from government sources derived through the Veterans Health Administration (VHA), and private sources of data from IBM MarketScan and Optum, using social network analysis. We analyzed a battery of research impact measures as a function of the data sources. Other main predictors were topic clusters and authors’ social influence. Additionally, we conducted key informant interviews (KII) with a purposive sample of high impact researchers who have knowledge of the data. We then compiled findings of KIIs into two case studies to provide a rich understanding of drivers of research impact. RESULTS: Analysis of 1,907 peer-reviewed publications using VHA, IBM MarketScan and Optum found that the overall research enterprise was highly dynamic and growing over time. With less than 4 years of observation, research productivity, use of machine learning (ML), natural language processing (NLP), and the Journal Impact Factor showed substantial growth. Studies that used ML and NLP, however, showed limited visibility. After adjustments, VHA studies had generally higher impact (10% and 27% higher annualized Google citation rates) compared to MarketScan and Optum (p<0.001 for both). Analysis of co-authorship networks showed that no single social actor, either a community of scientists or institutions, was dominating. Other key opportunities to achieve high impact based on KIIs include methodological innovations, under-studied populations and predictive modeling based on rich clinical data. CONCLUSIONS: Big data for purposes of research analytics has grown within the three data sources studied between 2013 and 2016. Despite important challenges, the research community is reacting favorably to the opportunities offered both by big data and advanced analytic methods. Big data may be a logical and cost-efficient choice to emulate research initiatives where RCTs are not possible