Bioinformatics Tools for Improving Matching for Hematopoietic Stem Cell Transplantation

University of Minnesota M.S. thesis.August 2017. Major: Biomedical Informatics and Computational Biology. Advisor: Abeer Madbouly. 1 computer file (PDF); 57 pages + 2 supplementary files.Hematopoietic Stem Cell Transplantation (HSCT) is a curative therapy for multiple malignant and non-malignant blood disorders. Multiple opportunities exist for facilitating and improving the accuracy of matching potential donors with patients in need of HSCT. The global donor pool does not adequately represent many regions of the world; therefore, donor searches would benefit from the haplotype analysis and modeling of underserved populations. Utilizing sequence data in matching algorithms also has potential to improve HSCT for patients in need. We developed the Gene Feature Enumeration (GFE) ecosystem to supplement the current HLA nomenclature by retaining all sequence data, hence enhancing matching precision. To improve the global donor pool, we performed a haplotype frequency analysis and registry modeling on the Ezer Mizion registry in Israel. Combining all these bioinformatics tools provides invaluable resources for unrelated donor registries to help serve HSCT patients worldwide

Relationship of Race/Ethnicity and Survival after Single Umbilical Cord Blood Transplantation for Adults and Children with Leukemia and Myelodysplastic Syndromes

The relationship of race/ethnicity with outcomes of umbilical cord blood transplantation (UCBT) is not well known. We analyzed the association between race/ethnicity and outcomes of unrelated single UCBT for leukemia and myelodysplastic syndromes. Our retrospective cohort study consisted of 885 adults and children (612 whites, 145 blacks, and 128 Hispanics) who received unrelated single UCBT for leukemia and myelodysplastic syndromes between 1995 and 2006 and were reported to the Center for International Blood and Marrow Transplant Research. A 5-6/6 HLA-matched unit with a total nucleated cell count infused of ≥2.5 × 107/kg was given to 40% white and 42% Hispanic, but only 21% black patients. Overall survival at 2 years was 44% for whites, 34% for blacks, and 46% for Hispanics (P = .008). In multivariate analysis adjusting for patient, disease, and treatment factors (including HLA match and cell dose), blacks had inferior overall survival (relative risk of death, 1.31; P = .02), whereas overall survival of Hispanics was similar (relative risk, 1.03; P = .81) to that of whites. For all patients, younger age, early-stage disease, use of units with higher cell dose, and performance status ≥80 were independent predictors of improved survival. Black patients and white patients infused with well-matched cords had comparable survival; similarly, black and white patients receiving units with adequate cell dose had similar survival. These results suggest that blacks have inferior survival to whites after single UCBT, but outcomes are improved when units with a higher cell dose are used

Neighborhood Cancerization: New Approaches Linking Social and Biological Mechanisms of Cancer

Novel multidisciplinary and multilevel approaches are required to link biologic and social mechanisms with cancer. We propose a new biosocial concept, â??neighborhood cancerization,â?? which postulates that residents of the same geographically-defined regions can be exposed to common unfavorable circumstances. These common neighborhood-level exposures can in turn have biological consequences that may result in an increased risk of cancer. Just as common â??molecular signaturesâ?? can differentiate tumor types, â??neighborhood signaturesâ?? can identify neighborhoods at increased risk for cancers of similar etiologic origins. Under a shared chronic stress hypothesis, we test the neighborhood cancerization theory by first determining the effect of neighborhood circumstances on telomere length (TL), a cellular marker of oxidative stress often implicated in cancer development at the population level. After addressing common methodologic concerns often cited in TL studies, we tested neighborhood and TL associations in a multi-racial, multi-center setting and in the context of individual-level stressors using quantile regression. We then developed and conducted a neighborhood-wide association study (NWAS) using all available U.S Census variables and the Pennsylvania State Cancer Registry in order to empirically identify common neighborhood factors related to prostate cancer. Our novel NWAS approach demonstrates how agnostic, high-dimensional data analyses can be used to identify neighborhoods and people at risk for high grade/high stage, aggressive prostate cancer. Our work has implications for health disparities research, and provides evidence to support the neighborhood cancerization hypothesis

Visions of Cardiomyocyte

In the field of cardiology, some of the most dramatic advances in recent years have come from understanding the molecular and cellular basis of cardiovascular disease. Knowledge of the pathological basis of disease in some cases allows the development of new strategies for prevention and treatment. This book was planned not only to convey new facts on cardiovascular diseases, but also to boost the excitement and challenges of research in the dynamic area of modern molecular and cellular biology of cardiology. The integration of multilevel biological data and the connection with clinical practice reveal the potential of personalized medicine, with future implications for prognosis, diagnosis, and management of cardiovascular diseases

The Human Cell Atlas White Paper

The Human Cell Atlas (HCA) will be made up of comprehensive reference maps of all human cells - the fundamental units of life - as a basis for understanding fundamental human biological processes and diagnosing, monitoring, and treating disease. It will help scientists understand how genetic variants impact disease risk, define drug toxicities, discover better therapies, and advance regenerative medicine. A resource of such ambition and scale should be built in stages, increasing in size, breadth, and resolution as technologies develop and understanding deepens. We will therefore pursue Phase 1 as a suite of flagship projects in key tissues, systems, and organs. We will bring together experts in biology, medicine, genomics, technology development and computation (including data analysis, software engineering, and visualization). We will also need standardized experimental and computational methods that will allow us to compare diverse cell and tissue types - and samples across human communities - in consistent ways, ensuring that the resulting resource is truly global. This document, the first version of the HCA White Paper, was written by experts in the field with feedback and suggestions from the HCA community, gathered during recent international meetings. The White Paper, released at the close of this yearlong planning process, will be a living document that evolves as the HCA community provides additional feedback, as technological and computational advances are made, and as lessons are learned during the construction of the atlas

Advancing the Science of Cancer in Latinos

This open access book gives an overview of the sessions, panel discussions, and outcomes of the Advancing the Science of Cancer in Latinos conference, held in February 2018 in San Antonio, Texas, USA, and hosted by the Mays Cancer Center and the Institute for Health Promotion Research at UT Health San Antonio. Latinos – the largest, youngest, and fastest-growing minority group in the United States – are expected to face a 142% rise in cancer cases in coming years. Although there has been substantial advancement in cancer prevention, screening, diagnosis, and treatment over the past few decades, addressing Latino cancer health disparities has not nearly kept pace with progress. The diverse and dynamic group of speakers and panelists brought together at the Advancing the Science of Cancer in Latinos conference provided in-depth insights as well as progress and actionable goals for Latino-focused basic science research, clinical best practices, community interventions, and what can be done by way of prevention, screening, diagnosis, and treatment of cancer in Latinos. These insights have been translated into the chapters included in this compendium; the chapters summarize the presentations and include current knowledge in the specific topic areas, identified gaps, and top priority areas for future cancer research in Latinos. Topics included among the chapters: Colorectal cancer disparities in Latinos: Genes vs. Environment Breast cancer risk and mortality in women of Latin American origin Differential cancer risk in Latinos: The role of diet Overcoming barriers for Latinos on cancer clinical trials Es tiempo: Engaging Latinas in cervical cancer research Emerging policies in U.S. health care Advancing the Science of Cancer in Latinos proves to be an indispensable resource offering key insights into actionable targets for basic science research, suggestions for clinical best practices and community interventions, and novel strategies and advocacy opportunities to reduce health disparities in Latino communities. It will find an engaged audience among researchers, academics, physicians and other healthcare professionals, patient advocates, students, and others with an interest in the broad field of Latino cancer

The EBMT Handbook

This Open Access edition of the European Society for Blood and Marrow Transplantation (EBMT) handbook addresses the latest developments and innovations in hematopoietic stem cell transplantation and cellular therapy. Consisting of 93 chapters, it has been written by 175 leading experts in the field. Discussing all types of stem cell and bone marrow transplantation, including haplo-identical stem cell and cord blood transplantation, it also covers the indications for transplantation, the management of early and late complications as well as the new and rapidly evolving field of cellular therapies. This book provides an unparalleled description of current practices to enhance readers’ knowledge and practice skills

Imaging Atherosclerosis.

Advances in atherosclerosis imaging technology and research have provided a range of diagnostic tools to characterize high-risk plaque in vivo; however, these important vascular imaging methods additionally promise great scientific and translational applications beyond this quest. When combined with conventional anatomic- and hemodynamic-based assessments of disease severity, cross-sectional multimodal imaging incorporating molecular probes and other novel noninvasive techniques can add detailed interrogation of plaque composition, activity, and overall disease burden. In the catheterization laboratory, intravascular imaging provides unparalleled access to the world beneath the plaque surface, allowing tissue characterization and measurement of cap thickness with micrometer spatial resolution. Atherosclerosis imaging captures key data that reveal snapshots into underlying biology, which can test our understanding of fundamental research questions and shape our approach toward patient management. Imaging can also be used to quantify response to therapeutic interventions and ultimately help predict cardiovascular risk. Although there are undeniable barriers to clinical translation, many of these hold-ups might soon be surpassed by rapidly evolving innovations to improve image acquisition, coregistration, motion correction, and reduce radiation exposure. This article provides a comprehensive review of current and experimental atherosclerosis imaging methods and their uses in research and potential for translation to the clinic.J.M.T. is supported by a Wellcome Trust research training fellowship (104492/Z/14/Z). M.D is supported by the British Heart Foundation (FS/14/78/31020). N.R.E. is supported by a research training fellowship from the Dunhill Medical Trust (RTF44/0114). A.J.B. is supported by the British Heart Foundation. J.H.F.R. is part-supported by the HEFCE, the NIHR Cambridge Biomedical Research Centre, the British Heart Foundation, and the Wellcome Trust.This is the final version of the article. It first appeared from the American Heart Association via http://dx.doi.org/10.1161/CIRCRESAHA.115.30624