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University of Texas MD Anderson Cancer Center
Statistical Issues in Proteomic Research
Jeffrey S. Morris Thu, 31 Jul 2008 11:03:24 -0700
Microproteomics: Analysis of protein diversity in small samples
Howard B. Gutstein Fri, 13 Jun 2008 14:38:53 -0700
Proteomics, the large-scale study of protein expression in organisms, offers the potential to evaluate global changes in protein expression and their post-translational modifications that take place in response to normal or pathological stimuli. One challenge has been the requirement for substantial amounts of tissue in order to perform comprehensive proteomic characterization. In heterogeneous tissues, such as brain, this has limited the application of proteomic methodologies. Efforts to adapt standard methods of tissue sampling, protein extraction, arraying, and identification are reviewed, with an emphasis on those appropriate to smaller samples ranging in size from several microliters down to single cells. The effects of miniaturization on these analyses are highlighted using neuroscience-related examples, as are statistical issues unique to the high-dimensional datasets generated by proteomic experiments.
Pinnacle: A Fast, Automatic Method for Detecting and Quantifying Protein Spots in 2-Dimensional Gel Electrophoresis Data
Jeffrey S. Morris Tue, 04 Dec 2007 09:44:53 -0800
Motivation: One of the key limitations for proteomic studies using 2-dimensional gel electrophoresis (2DE) is the lack of rapid, robust, and reproducible methods for detecting, matching, and quantifying protein spots. The most commonly used approaches involve first detecting spots and drawing spot boundaries on individual gels, then matching spots across gels, and finally quantifying each spot by calculating normalized spot volumes. This approach is time con-suming, error-prone, and frequently requires extensive manual edit-ing, which can unintentionally introduce bias into the results.Results: We introduce a new method for spot detection and quanti-fication called Pinnacle that is automatic, quick, sensitive and spe-cific, and yields spot quantifications that are reliable and precise. This method incorporates a spot definition that is based on simple, straightforward criteria rather than complex arbitrary definitions, and results in no missing data. Using dilution series for validation, we demonstrate Pinnacle outperformed two well-established 2DE analysis packages, proving to be more accurate and yielding smaller CVs. More accurate quantifications may lead to increased power for detecting differentially expressed spots, an idea supported by the results of our group comparison experiment. Our fast, automatic analysis method makes it feasible to conduct very large 2DE-based proteomic studies that are adequately powered to find important protein expression differences.Availability: Matlab code to implement Pinnacle is available from the authors upon request for non-commercial use.
Laser capture sampling and analytical issues in proteomics
Howard Gutstein Tue, 04 Dec 2007 09:35:54 -0800
Proteomics holds the promise of evaluating global changes in protein expression and post-translational modificaiton in response to environmental stimuli. However, difficulties in achieving cellular anatomic resolution and extracting specific types of proteins from cells have limited the efficacy of these techniques. Laser capture microdissection has provided a solution to the problem of anatomical resolution in tissues. New extraction methodologies have expanded the range of proteins identified in subsequent analyses. This review will examine the application of laser capture microdissection to proteomic tissue sampling, and subsequent extraction of these samples for differential expression analysis. Statistical and other quantitative issues important for the analysis of the highly complex datasets generated are also reviewed.
Statistical contributions to proteomic research
Jeffrey S. Morris Wed, 04 Apr 2007 12:55:09 -0700
Proteomic profiling has the potential to impact the diagnosis, prognosis, and treatment of various diseases. A number of different proteomic technologies are available that allow us to look at many proteins at once, and all of them yield complex data that raise significant quantitative challenges. Inadequate attention to these quantitative issues can prevent these studies from achieving their desired goals, and can even lead to invalid results. In this chapter, we describe various ways the involvement of statisticians or other quantitative scientists in the study team can contribute to the success of proteomic research, and we outline some of the key statistical principles that should guide the experimental design and analysis of such studies.
Wavelet-based functional mixed model analysis: Computational considerations
Richard C. Herrick Wed, 04 Apr 2007 12:48:45 -0700
Wavelet-based Functional Mixed Models is a new Bayesian method extending mixed models to irregular functional data (Morris and Carroll, JRSS-B, 2006). These data sets are typically very large and can quickly run into memory and time constraints unless these issues are carefully dealt with in the software. We reduce runtime by 1.) identifying and optimizing hotspots, 2.) using wavelet compression to do less computation with minimal impact on results, and 3.) dividing the code into multiple executables to be run in parallel using a grid computing resource. We discuss rules of thumb for estimating memory requirements and computation times in terms of model and data set parameters. We present examples and benchmarks demonstrating that it is practical to analyze very large data sets with readily available computing resources. This code is freely available on our website.
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Statistical Issues in Proteomic Research
Jeffrey S. Morris Thu, 31 Jul 2008 11:03:24 -0700
Microproteomics: Analysis of protein diversity in small samples
Howard B. Gutstein Fri, 13 Jun 2008 14:38:53 -0700
Proteomics, the large-scale study of protein expression in organisms, offers the potential to evaluate global changes in protein expression and their post-translational modifications that take place in response to normal or pathological stimuli. One challenge has been the requirement for substantial amounts of tissue in order to perform comprehensive proteomic characterization. In heterogeneous tissues, such as brain, this has limited the application of proteomic methodologies. Efforts to adapt standard methods of tissue sampling, protein extraction, arraying, and identification are reviewed, with an emphasis on those appropriate to smaller samples ranging in size from several microliters down to single cells. The effects of miniaturization on these analyses are highlighted using neuroscience-related examples, as are statistical issues unique to the high-dimensional datasets generated by proteomic experiments.
Pinnacle: A Fast, Automatic Method for Detecting and Quantifying Protein Spots in 2-Dimensional Gel Electrophoresis Data
Jeffrey S. Morris Tue, 04 Dec 2007 09:44:53 -0800
Motivation: One of the key limitations for proteomic studies using 2-dimensional gel electrophoresis (2DE) is the lack of rapid, robust, and reproducible methods for detecting, matching, and quantifying protein spots. The most commonly used approaches involve first detecting spots and drawing spot boundaries on individual gels, then matching spots across gels, and finally quantifying each spot by calculating normalized spot volumes. This approach is time con-suming, error-prone, and frequently requires extensive manual edit-ing, which can unintentionally introduce bias into the results.Results: We introduce a new method for spot detection and quanti-fication called Pinnacle that is automatic, quick, sensitive and spe-cific, and yields spot quantifications that are reliable and precise. This method incorporates a spot definition that is based on simple, straightforward criteria rather than complex arbitrary definitions, and results in no missing data. Using dilution series for validation, we demonstrate Pinnacle outperformed two well-established 2DE analysis packages, proving to be more accurate and yielding smaller CVs. More accurate quantifications may lead to increased power for detecting differentially expressed spots, an idea supported by the results of our group comparison experiment. Our fast, automatic analysis method makes it feasible to conduct very large 2DE-based proteomic studies that are adequately powered to find important protein expression differences.Availability: Matlab code to implement Pinnacle is available from the authors upon request for non-commercial use.
Laser capture sampling and analytical issues in proteomics
Howard Gutstein Tue, 04 Dec 2007 09:35:54 -0800
Proteomics holds the promise of evaluating global changes in protein expression and post-translational modificaiton in response to environmental stimuli. However, difficulties in achieving cellular anatomic resolution and extracting specific types of proteins from cells have limited the efficacy of these techniques. Laser capture microdissection has provided a solution to the problem of anatomical resolution in tissues. New extraction methodologies have expanded the range of proteins identified in subsequent analyses. This review will examine the application of laser capture microdissection to proteomic tissue sampling, and subsequent extraction of these samples for differential expression analysis. Statistical and other quantitative issues important for the analysis of the highly complex datasets generated are also reviewed.
Statistical contributions to proteomic research
Jeffrey S. Morris Wed, 04 Apr 2007 12:55:09 -0700
Proteomic profiling has the potential to impact the diagnosis, prognosis, and treatment of various diseases. A number of different proteomic technologies are available that allow us to look at many proteins at once, and all of them yield complex data that raise significant quantitative challenges. Inadequate attention to these quantitative issues can prevent these studies from achieving their desired goals, and can even lead to invalid results. In this chapter, we describe various ways the involvement of statisticians or other quantitative scientists in the study team can contribute to the success of proteomic research, and we outline some of the key statistical principles that should guide the experimental design and analysis of such studies.
Wavelet-based functional mixed model analysis: Computational considerations
Richard C. Herrick Wed, 04 Apr 2007 12:48:45 -0700
Wavelet-based Functional Mixed Models is a new Bayesian method extending mixed models to irregular functional data (Morris and Carroll, JRSS-B, 2006). These data sets are typically very large and can quickly run into memory and time constraints unless these issues are carefully dealt with in the software. We reduce runtime by 1.) identifying and optimizing hotspots, 2.) using wavelet compression to do less computation with minimal impact on results, and 3.) dividing the code into multiple executables to be run in parallel using a grid computing resource. We discuss rules of thumb for estimating memory requirements and computation times in terms of model and data set parameters. We present examples and benchmarks demonstrating that it is practical to analyze very large data sets with readily available computing resources. This code is freely available on our website.
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CancerBACUP: Skin Cancer Information Centre: Information about skin cancer, including causes, symptoms, diagnosis, treatments, side effects and further resources.
CancerIndex.org: Skin: Information and links about specific types of these malignancies.
eMedicine Health: Skin Cancer: Skin cancer is the most common of all human cancers. Some form of skin cancer is diagnosed in more than 1 million people in the United States each year. Cancer ...
GatorSHADE: Located in Gainesville Florida at the University of Florida's College of Nursing, the GatorSHADE Program promotes provides public school curriculum and other materials to promote public awareness on the topic of skin cancer.
Introduction to Skin Cancer: South Seas Trading Company
MedicineNet: Skin Cancer: Learn the types of skin cancer (basal cell carcinoma, squamous cell carcinoma, and melanoma), their causes, symptoms, treatments, and prevention techniques. Get the facts about sun exposure and sunscreen.
Memorial Sloan-Kettering: Skin Cancer: Each year more than a million people in the United States are diagnosed with the most common forms of skin cancer: basal cell carcinoma and squamous cell carcinoma. These two diseases are most often grouped as non-melanoma skin cancers.
Project S.A.F.E.T.Y.: Educational CD-ROM about skin cancer awareness designed for fourth to ninth grade teachers through the M.D. Anderson Cancer Center in Houston, Texas.
Skin Cancer Guide.ca: Skin Cancer Guide: Symptoms, detection, prevention, and treatment options for Basal Cell Cancer, sBCC (Superficial Basal Cell Cancer), Squamous Cell Cancer, Melanoma, and Actinic Keratosis
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Sun Protection: Explains the dangers of ultraviolet radiation, the factors affecting levels, and how to avoid exposure. Includes information on different skin types and how to check for damage.
Sunscreens And Cancer: A review of the evidence linking the use of sunscreens to an increased risk of melanoma and skin cancer (basal carcinoma and squamous cell carcinoma)
The Skin Cancer Foundation: Non-profit organization located in New York City.
The Sun and Your Skin: fresh information about sun protection skin care and skin disorders sun news and benefits of light. - Prevention Science
Understanding Skin Cancer: Understanding Skin Cancer - This information has been written to help you understand more about the two most common types of skin cancer: basal cell carcinoma (BCC) and squamous cell carcinoma (SCC).
University of Maryland Medicine Skin Cancer Guide: Health guide containing skin cancer information, presented by University of Maryland Medicine
Women's Cancer Information Project: Skin Cancer: Information from the European Institute of Women's Health.
Yahoo Health: Skin Cancer: Information including basic facts, risks, prevention, diagnosis and treatment.
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