252 research outputs found
New Statistical Algorithms for the Analysis of Mass Spectrometry Time-Of-Flight Mass Data with Applications in Clinical Diagnostics
Mass spectrometry (MS) based techniques have emerged as a standard forlarge-scale protein analysis. The ongoing progress in terms of more sensitive
machines and improved data analysis algorithms led to a constant expansion of
its fields of applications. Recently, MS was introduced into clinical proteomics
with the prospect of early disease detection using proteomic pattern matching.
Analyzing biological samples (e.g. blood) by mass spectrometry generates
mass spectra that represent the components (molecules) contained in a
sample as masses and their respective relative concentrations.
In this work, we are interested in those components that are constant within a
group of individuals but differ much between individuals of two distinct groups.
These distinguishing components that dependent on a particular medical condition
are generally called biomarkers. Since not all biomarkers found by the
algorithms are of equal (discriminating) quality we are only interested in a
small biomarker subset that - as a combination - can be used as a
fingerprint for a disease. Once a fingerprint for a particular disease
(or medical condition) is identified, it can be used in clinical diagnostics to
classify unknown spectra.
In this thesis we have developed new algorithms for automatic extraction of
disease specific fingerprints from mass spectrometry data. Special emphasis has
been put on designing highly sensitive methods with respect to signal detection.
Thanks to our statistically based approach our methods are able to
detect signals even below the noise level inherent in data acquired by common MS
machines, such as hormones.
To provide access to these new classes of algorithms to collaborating groups
we have created a web-based analysis platform that provides all necessary
interfaces for data transfer, data analysis and result inspection.
To prove the platform's practical relevance it has been utilized in several
clinical studies two of which are presented in this thesis. In these studies it
could be shown that our platform is superior to commercial systems with respect
to fingerprint identification. As an outcome of these studies several
fingerprints for different cancer types (bladder, kidney, testicle, pancreas,
colon and thyroid) have been detected and validated. The clinical partners in
fact emphasize that these results would be impossible with a less sensitive
analysis tool (such as the currently available systems).
In addition to the issue of reliably finding and handling signals in noise we
faced the problem to handle very large amounts of data, since an average dataset
of an individual is about 2.5 Gigabytes in size and we have data of hundreds to
thousands of persons. To cope with these large datasets, we developed a new
framework for a heterogeneous (quasi) ad-hoc Grid - an infrastructure that
allows to integrate thousands of computing resources (e.g. Desktop Computers,
Computing Clusters or specialized hardware, such as IBM's Cell Processor in a
Playstation 3)
Biometrics
Biometrics uses methods for unique recognition of humans based upon one or more intrinsic physical or behavioral traits. In computer science, particularly, biometrics is used as a form of identity access management and access control. It is also used to identify individuals in groups that are under surveillance. The book consists of 13 chapters, each focusing on a certain aspect of the problem. The book chapters are divided into three sections: physical biometrics, behavioral biometrics and medical biometrics. The key objective of the book is to provide comprehensive reference and text on human authentication and people identity verification from both physiological, behavioural and other points of view. It aims to publish new insights into current innovations in computer systems and technology for biometrics development and its applications. The book was reviewed by the editor Dr. Jucheng Yang, and many of the guest editors, such as Dr. Girija Chetty, Dr. Norman Poh, Dr. Loris Nanni, Dr. Jianjiang Feng, Dr. Dongsun Park, Dr. Sook Yoon and so on, who also made a significant contribution to the book
Complexity, Emergent Systems and Complex Biological Systems:\ud Complex Systems Theory and Biodynamics. [Edited book by I.C. Baianu, with listed contributors (2011)]
An overview is presented of System dynamics, the study of the behaviour of complex systems, Dynamical system in mathematics Dynamic programming in computer science and control theory, Complex systems biology, Neurodynamics and Psychodynamics.\u
Life in a drop of water
Thesis (Ph. D.)--Massachusetts Institute of Technology, Dept. of Biology, 2009.Cataloged from PDF version of thesis.Includes bibliographical references.The last century of biology brought a revolution to our understanding of life at the molecular level; the last decade, a widening re-evaluation of the claim that understanding gained in vitro could reflect the true complexities in vivo and in situ. I present the results of two projects, one grounded in each strain of biological thought. In the first, I statistically analyze and biochemically map the functional groups making intramolecular interactions that permit activity in an in vitro-evolved RNA enzyme, the class I ligase ribozyme; although this ribozyme, derived from random sequence, has never been a part of any organism, understanding its structure and biochemistry is a key step on one of the few relatively well-defined paths to understanding the origins of life. I identify key residues in the ribozyme and present biochemical evidence in support of its proposed catalytic mechanism. In the second study, the interactions at issue are those between an organism, the cyanobacterium Prochlorococcus, and its environment, the oligotrophic ocean. Prochlorococcus has been found living in very different oxygen regimes in the open ocean; I hypothesized that these different oxygen levels might primarily affect Prochlorococcus growth through the competition between oxygen and carbon dioxide for binding to the carbon-fixing enzyme Rubisco. I characterize the transcriptional and growth response of Prochlorococcus strain MED4 to limitations on its supply of oxygen and inorganic carbon, finding indications that oxygen contributes to the health of the carbon-limited cell through two photo protective pathways.(cont.) I discuss these responses in the context of both the studied responses of Prochlorococcus to other extreme environmental stressors and the normal modulations necessary for life amid daily flux.by Sarah Catherine Bagby.Ph.D
Bioinformatics
This book is divided into different research areas relevant in Bioinformatics such as biological networks, next generation sequencing, high performance computing, molecular modeling, structural bioinformatics, molecular modeling and intelligent data analysis. Each book section introduces the basic concepts and then explains its application to problems of great relevance, so both novice and expert readers can benefit from the information and research works presented here
Structural studies of the DNA partitioning protein IncC from the plasmid RK2
Plasmid DNA partitioning is a crucial process for the transfer of at least a single copy of plasmid to the daughter cells during bacterial cell division. Partitioning for various low-copy number plasmids involves a DNA-binding protein (ParB), a centromere-like DNA site ( parS) and a ParA-family protein. Interestingly, the RK2 plasmid encodes two ParA proteins of different lengths. The longer protein is IncC1 (364 a.a), while IncC2 lacks a N- terminal domain of 105 amino acids (IncC NTD). The secondary structure of IncC NTD by NMR spectroscopy and other biophysical methods has been determined as random coil. It appears to bind DNA weakly and non-specifically. The expression and purification of IncC1 and IncC2 proteins was optimized. The two proteins and IncC NTD were characterized using various biophysical methods including Circular Dichroism, Analytical Ultracentrifugation, Small Angle X-ray Scattering, Size Exclusion Chromatography-Multi Angle Light Scattering, and EMSAs. Bacterial two hybrid assays and chemical crosslinking showed the two IncC proteins form homo- and hetero-dimers and interact with KorB protein. IncC1 and IncC2 proteins bind to DNA, non-specifically. IncC1 binds DNA weakly in the absence of nucleotides but IncC2 protein was found to bind DNA only in the presence of nucleotides (ADP, ATP)
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Laboratory Directed Research and Development Annual Report - Fiscal Year 2000
The projects described in this report represent the Laboratory's investment in its future and are vital to maintaining the ability to develop creative solutions for the scientific and technical challenges faced by DOE and the nation. In accordance with DOE guidelines, the report provides, a) a director's statement, b) an overview of the laboratory's LDRD program, including PNNL's management process and a self-assessment of the program, c) a five-year project funding table, and d) project summaries for each LDRD project
2002 Fourteenth Annual IMSA Presentation Day
As you begin to turn the pages and learn about the extraordinary research work of IMSA\u27s young investigators, I hope you will begin to see what is possible.https://digitalcommons.imsa.edu/archives_sir/1023/thumbnail.jp
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