Model Based Hypothesis Testing In Biomedicine

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Model Based Hypothesis Testing In Biomedicine

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Author : Rikard Johansson
language : en
Publisher: Linköping University Electronic Press
Release Date : 2017-10-03

Model Based Hypothesis Testing In Biomedicine written by Rikard Johansson and has been published by Linköping University Electronic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-10-03 with categories.

The utilization of mathematical tools within biology and medicine has traditionally been less widespread compared to other hard sciences, such as physics and chemistry. However, an increased need for tools such as data processing, bioinformatics, statistics, and mathematical modeling, have emerged due to advancements during the last decades. These advancements are partly due to the development of high-throughput experimental procedures and techniques, which produce ever increasing amounts of data. For all aspects of biology and medicine, these data reveal a high level of inter-connectivity between components, which operate on many levels of control, and with multiple feedbacks both between and within each level of control. However, the availability of these large-scale data is not synonymous to a detailed mechanistic understanding of the underlying system. Rather, a mechanistic understanding is gained first when we construct a hypothesis, and test its predictions experimentally. Identifying interesting predictions that are quantitative in nature, generally requires mathematical modeling. This, in turn, requires that the studied system can be formulated into a mathematical model, such as a series of ordinary differential equations, where different hypotheses can be expressed as precise mathematical expressions that influence the output of the model. Within specific sub-domains of biology, the utilization of mathematical models have had a long tradition, such as the modeling done on electrophysiology by Hodgkin and Huxley in the 1950s. However, it is only in recent years, with the arrival of the field known as systems biology that mathematical modeling has become more commonplace. The somewhat slow adaptation of mathematical modeling in biology is partly due to historical differences in training and terminology, as well as in a lack of awareness of showcases illustrating how modeling can make a difference, or even be required, for a correct analysis of the experimental data. In this work, I provide such showcases by demonstrating the universality and applicability of mathematical modeling and hypothesis testing in three disparate biological systems. In Paper II, we demonstrate how mathematical modeling is necessary for the correct interpretation and analysis of dominant negative inhibition data in insulin signaling in primary human adipocytes. In Paper III, we use modeling to determine transport rates across the nuclear membrane in yeast cells, and we show how this technique is superior to traditional curve-fitting methods. We also demonstrate the issue of population heterogeneity and the need to account for individual differences between cells and the population at large. In Paper IV, we use mathematical modeling to reject three hypotheses concerning the phenomenon of facilitation in pyramidal nerve cells in rats and mice. We also show how one surviving hypothesis can explain all data and adequately describe independent validation data. Finally, in Paper I, we develop a method for model selection and discrimination using parametric bootstrapping and the combination of several different empirical distributions of traditional statistical tests. We show how the empirical log-likelihood ratio test is the best combination of two tests and how this can be used, not only for model selection, but also for model discrimination. In conclusion, mathematical modeling is a valuable tool for analyzing data and testing biological hypotheses, regardless of the underlying biological system. Further development of modeling methods and applications are therefore important since these will in all likelihood play a crucial role in all future aspects of biology and medicine, especially in dealing with the burden of increasing amounts of data that is made available with new experimental techniques. Användandet av matematiska verktyg har inom biologi och medicin traditionellt sett varit mindre utbredd jämfört med andra ämnen inom naturvetenskapen, såsom fysik och kemi. Ett ökat behov av verktyg som databehandling, bioinformatik, statistik och matematisk modellering har trätt fram tack vare framsteg under de senaste decennierna. Dessa framsteg är delvis ett resultat av utvecklingen av storskaliga datainsamlingstekniker. Inom alla områden av biologi och medicin så har dessa data avslöjat en hög nivå av interkonnektivitet mellan komponenter, verksamma på många kontrollnivåer och med flera återkopplingar både mellan och inom varje nivå av kontroll. Tillgång till storskaliga data är emellertid inte synonymt med en detaljerad mekanistisk förståelse för det underliggande systemet. Snarare uppnås en mekanisk förståelse först när vi bygger en hypotes vars prediktioner vi kan testa experimentellt. Att identifiera intressanta prediktioner som är av kvantitativ natur, kräver generellt sett matematisk modellering. Detta kräver i sin tur att det studerade systemet kan formuleras till en matematisk modell, såsom en serie ordinära differentialekvationer, där olika hypoteser kan uttryckas som precisa matematiska uttryck som påverkar modellens output. Inom vissa delområden av biologin har utnyttjandet av matematiska modeller haft en lång tradition, såsom den modellering gjord inom elektrofysiologi av Hodgkin och Huxley på 1950‑talet. Det är emellertid just på senare år, med ankomsten av fältet systembiologi, som matematisk modellering har blivit ett vanligt inslag. Den något långsamma adapteringen av matematisk modellering inom biologi är bl.a. grundad i historiska skillnader i träning och terminologi, samt brist på medvetenhet om exempel som illustrerar hur modellering kan göra skillnad och faktiskt ofta är ett krav för en korrekt analys av experimentella data. I detta arbete tillhandahåller jag sådana exempel och demonstrerar den matematiska modelleringens och hypotestestningens allmängiltighet och tillämpbarhet i tre olika biologiska system. I Arbete II visar vi hur matematisk modellering är nödvändig för en korrekt tolkning och analys av dominant-negativ-inhiberingsdata vid insulinsignalering i primära humana adipocyter. I Arbete III använder vi modellering för att bestämma transporthastigheter över cellkärnmembranet i jästceller, och vi visar hur denna teknik är överlägsen traditionella kurvpassningsmetoder. Vi demonstrerar också frågan om populationsheterogenitet och behovet av att ta hänsyn till individuella skillnader mellan celler och befolkningen som helhet. I Arbete IV använder vi matematisk modellering för att förkasta tre hypoteser om hur fenomenet facilitering uppstår i pyramidala nervceller hos råttor och möss. Vi visar också hur en överlevande hypotes kan beskriva all data, inklusive oberoende valideringsdata. Slutligen utvecklar vi i Arbete I en metod för modellselektion och modelldiskriminering med hjälp av parametrisk ”bootstrapping” samt kombinationen av olika empiriska fördelningar av traditionella statistiska tester. Vi visar hur det empiriska ”log-likelihood-ratio-testet” är den bästa kombinationen av två tester och hur testet är applicerbart, inte bara för modellselektion, utan också för modelldiskriminering. Sammanfattningsvis är matematisk modellering ett värdefullt verktyg för att analysera data och testa biologiska hypoteser, oavsett underliggande biologiskt system. Vidare utveckling av modelleringsmetoder och tillämpningar är därför viktigt eftersom dessa sannolikt kommer att spela en avgörande roll i framtiden för biologi och medicin, särskilt när det gäller att hantera belastningen från ökande datamängder som blir tillgänglig med nya experimentella tekniker.

Biosimulation In Biomedical Research Health Care And Drug Development

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Author : Erik Mosekilde
language : en
Publisher: Springer Science & Business Media
Release Date : 2011-11-01

Biosimulation In Biomedical Research Health Care And Drug Development written by Erik Mosekilde and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2011-11-01 with Medical categories.

Biosimulation is an approach to biomedical research and the treatment of patients in which computer modeling goes hand in hand with experimental and clinical work. Constructed models are used to interpret experimental results and to accumulate information from experiment to experiment. This book explains the concepts used in the modeling of biological phenomena and goes on to present a series of well-documented models of the regulation of various genetic, cellular and physiological processes. The way how the use of computer models allows optimization of cancer treatment for individual patients is discussed and models of interacting nerve cells that can be used to design new treatments for patients with Parkinson's disease are explained. Furthermore this volume provides an overview on the use of models in industry, and presents the view of regulatory agencies on the topic.

Empirical Likelihood Methods In Biomedicine And Health

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Author : Albert Vexler
language : en
Publisher: CRC Press
Release Date : 2018-09-03

Empirical Likelihood Methods In Biomedicine And Health written by Albert Vexler and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2018-09-03 with Mathematics categories.

Empirical Likelihood Methods in Biomedicine and Health provides a compendium of nonparametric likelihood statistical techniques in the perspective of health research applications. It includes detailed descriptions of the theoretical underpinnings of recently developed empirical likelihood-based methods. The emphasis throughout is on the application of the methods to the health sciences, with worked examples using real data. Provides a systematic overview of novel empirical likelihood techniques. Presents a good balance of theory, methods, and applications. Features detailed worked examples to illustrate the application of the methods. Includes R code for implementation. The book material is attractive and easily understandable to scientists who are new to the research area and may attract statisticians interested in learning more about advanced nonparametric topics including various modern empirical likelihood methods. The book can be used by graduate students majoring in biostatistics, or in a related field, particularly for those who are interested in nonparametric methods with direct applications in Biomedicine.

Statistical Modeling In Biomedical Research

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Author : Yichuan Zhao
language : en
Publisher: Springer Nature
Release Date : 2020-03-19

Statistical Modeling In Biomedical Research written by Yichuan Zhao and has been published by Springer Nature this book supported file pdf, txt, epub, kindle and other format this book has been release on 2020-03-19 with Medical categories.

This edited collection discusses the emerging topics in statistical modeling for biomedical research. Leading experts in the frontiers of biostatistics and biomedical research discuss the statistical procedures, useful methods, and their novel applications in biostatistics research. Interdisciplinary in scope, the volume as a whole reflects the latest advances in statistical modeling in biomedical research, identifies impactful new directions, and seeks to drive the field forward. It also fosters the interaction of scholars in the arena, offering great opportunities to stimulate further collaborations. This book will appeal to industry data scientists and statisticians, researchers, and graduate students in biostatistics and biomedical science. It covers topics in: Next generation sequence data analysis Deep learning, precision medicine, and their applications Large scale data analysis and its applications Biomedical research and modeling Survival analysis with complex data structure and its applications.

Statistical Advances In The Biomedical Sciences

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Author : Atanu Biswas
language : en
Publisher: John Wiley & Sons
Release Date : 2008-01-02

Statistical Advances In The Biomedical Sciences written by Atanu Biswas and has been published by John Wiley & Sons this book supported file pdf, txt, epub, kindle and other format this book has been release on 2008-01-02 with Mathematics categories.

The Most Comprehensive and Cutting-Edge Guide to Statistical Applications in Biomedical Research With the increasing use of biotechnology in medical research and the sophisticated advances in computing, it has become essential for practitioners in the biomedical sciences to be fully educated on the role statistics plays in ensuring the accurate analysis of research findings. Statistical Advances in the Biomedical Sciences explores the growing value of statistical knowledge in the management and comprehension of medical research and, more specifically, provides an accessible introduction to the contemporary methodologies used to understand complex problems in the four major areas of modern-day biomedical science: clinical trials, epidemiology, survival analysis, and bioinformatics. Composed of contributions from eminent researchers in the field, this volume discusses the application of statistical techniques to various aspects of modern medical research and illustrates how these methods ultimately prove to be an indispensable part of proper data collection and analysis. A structural uniformity is maintained across all chapters, each beginning with an introduction that discusses general concepts and the biomedical problem under focus and is followed by specific details on the associated methods, algorithms, and applications. In addition, each chapter provides a summary of the main ideas and offers a concluding remarks section that presents novel ideas, approaches, and challenges for future research. Complete with detailed references and insight on the future directions of biomedical research, Statistical Advances in the Biomedical Sciences provides vital statistical guidance to practitioners in the biomedical sciences while also introducing statisticians to new, multidisciplinary frontiers of application. This text is an excellent reference for graduate- and PhD-level courses in various areas of biostatistics and the medical sciences and also serves as a valuable tool for medical researchers, statisticians, public health professionals, and biostatisticians.

Advances In Processing And Pattern Analysis Of Biological Signals

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Author : I. Gath
language : en
Publisher: Springer Science & Business Media
Release Date : 2013-06-29

Advances In Processing And Pattern Analysis Of Biological Signals written by I. Gath and has been published by Springer Science & Business Media this book supported file pdf, txt, epub, kindle and other format this book has been release on 2013-06-29 with Technology & Engineering categories.

In recent years there has been rapid progress in the development of signal processing in general, and more specifically in the application of signal processing and pattern analysis to biological signals. Techniques, such as parametric and nonparametric spectral estimation, higher order spectral estimation, time-frequency methods, wavelet transform, and identifi cation of nonlinear systems using chaos theory, have been successfully used to elucidate basic mechanisms of physiological and mental processes. Similarly, biological signals recorded during daily medical practice for clinical diagnostic procedures, such as electroen cephalograms (EEG), evoked potentials (EP), electromyograms (EMG) and electrocardio grams (ECG), have greatly benefitted from advances in signal processing. In order to update researchers, graduate students, and clinicians, on the latest developments in the field, an International Symposium on Processing and Pattern Analysis of Biological Signals was held at the Technion-Israel Institute of Technology, during March 1995. This book contains 27 papers delivered during the symposium. The book follows the five sessions of the symposium. The first section, Processing and Pattern Analysis of Normal and Pathological EEG, accounts for some of the latest developments in the area of EEG processing, namely: time varying parametric modeling; non-linear dynamic modeling of the EEG using chaos theory; Markov analysis; delay estimation using adaptive least-squares filtering; and applications to the analysis of epileptic EEG, EEG recorded from psychiatric patients, and sleep EEG.

Computational Methods In Biomedical Research

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Author : Ravindra Khattree
language : en
Publisher: CRC Press
Release Date : 2007-12-12

Computational Methods In Biomedical Research written by Ravindra Khattree and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2007-12-12 with Mathematics categories.

Continuing advances in biomedical research and statistical methods call for a constant stream of updated, cohesive accounts of new developments so that the methodologies can be properly implemented in the biomedical field. Responding to this need, Computational Methods in Biomedical Research explores important current and emerging computational statistical methods that are used in biomedical research. Written by active researchers in the field, this authoritative collection covers a wide range of topics. It introduces each topic at a basic level, before moving on to more advanced discussions of applications. The book begins with microarray data analysis, machine learning techniques, and mass spectrometry-based protein profiling. It then uses state space models to predict US cancer mortality rates and provides an overview of the application of multistate models in analyzing multiple failure times. The book also describes various Bayesian techniques, the sequential monitoring of randomization tests, mixed-effects models, and the classification rules for repeated measures data. The volume concludes with estimation methods for analyzing longitudinal data. Supplying the knowledge necessary to perform sophisticated statistical analyses, this reference is a must-have for anyone involved in advanced biomedical and pharmaceutical research. It will help in the quest to identify potential new drugs for the treatment of a variety of diseases.

Causal Inference In Statistics Social And Biomedical Sciences

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Author : Guido W. Imbens
language : en
Publisher: Cambridge University Press
Release Date : 2015-04-06

Causal Inference In Statistics Social And Biomedical Sciences written by Guido W. Imbens and has been published by Cambridge University Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2015-04-06 with Business & Economics categories.

This text presents statistical methods for studying causal effects and discusses how readers can assess such effects in simple randomized experiments.

Image Analysis And Modeling In Ophthalmology

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Author : Eddie Y. K. Ng
language : en
Publisher: CRC Press
Release Date : 2014-02-11

Image Analysis And Modeling In Ophthalmology written by Eddie Y. K. Ng and has been published by CRC Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2014-02-11 with Technology & Engineering categories.

Digital fundus images can effectively diagnose glaucoma and diabetes retinopathy, while infrared imaging can show changes in the vascular tissues. Likening the eye to the conventional camera, Image Analysis and Modeling in Ophthalmology explores the application of advanced image processing in ocular imaging. This book considers how images can be used to effectively diagnose ophthalmologic problems. It introduces multi-modality image processing algorithms as a means for analyzing subtle changes in the eye. It details eye imaging, textural imaging, and modeling, and highlights specific imaging and modeling techniques. The book covers the detection of diabetes retinopathy, glaucoma, anterior segment eye abnormalities, instruments on detection of glaucoma, and development of human eye models using computational fluid dynamics and heat transfer principles to predict inner temperatures of the eye from its surface temperature. It presents an ultrasound biomicroscopy (UBM) system for anterior chamber angle imaging and proposes an automated anterior segment eye disease classification system that can be used for early disease diagnosis and treatment management. It focuses on the segmentation of the blood vessels in high-resolution retinal images and describes the integration of the image processing methodologies in a web-based framework aimed at retinal analysis. The authors introduce the A-Levelset algorithm, explore the ARGALI system to calculate the cup-to-disc ratio (CDR), and describe the Singapore Eye Vessel Assessment (SIVA) system, a holistic tool which brings together various technologies from image processing and artificial intelligence to construct vascular models from retinal images. The text furnishes the working principles of mechanical and optical instruments for the diagnosis and healthcare administration of glaucoma, reviews state-of-the-art CDR calculation detail, and discusses the existing methods and databases. Image Analysis and Modeling in Ophthalmology includes the latest research development in the field of eye modeling and the multi-modality image processing techniques in ocular imaging. It addresses the differences, performance measures, advantages and disadvantages of various approaches, and provides extensive reviews on related fields.

Research In The Biomedical Sciences

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Author : Michael Williams
language : en
Publisher: Academic Press
Release Date : 2017-10-20

Research In The Biomedical Sciences written by Michael Williams and has been published by Academic Press this book supported file pdf, txt, epub, kindle and other format this book has been release on 2017-10-20 with Science categories.

Research in the Biomedical Sciences: Transparent and Reproducible documents the widespread concerns related to reproducibility in biomedical research and provides a best practices guide to effective and transparent hypothesis generation, experimental design, reagent standardization (including validation and authentication), statistical analysis, and data reporting. The book addresses issues in the perceived value of the existing peer review process and calls for the need for improved transparency in data reporting. It reflects new guidelines for publication that include manuscript checklists, replication/reproducibility initiatives, and the potential consequences for the biomedical research community and societal health and well-being if training, mentoring, and funding of new generations of researchers and incentives for publications are not improved. This book offers real world examples, insights, and solutions to provide a thought-provoking and timely resource for all those learning about, or engaged in, performing and supervising research across the biomedical sciences. - Provides a "big picture perspective on the scope of reproducibility issues and covers initiatives that have potential as effective solutions - Offers real-world research context for transparent, reproducible experimental design, execution and reporting of biomedical research with the potential to address aspects of the translational gap in drug discovery - Highlights the importance of reproducibility and the necessary changes in biomedical and pharmaceutical research training and incentives to ensure sustainability