1,327 research outputs found
Definition of valid proteomic biomarkers: a bayesian solution
Clinical proteomics is suffering from high hopes generated by reports on apparent biomarkers, most of which could not be later substantiated via validation. This has brought into focus the need for improved methods of finding a panel of clearly defined biomarkers. To examine this problem, urinary proteome data was collected from healthy adult males and females, and analysed to find biomarkers that differentiated between genders. We believe that models that incorporate sparsity in terms of variables are desirable for biomarker selection, as proteomics data typically contains a huge number of variables (peptides) and few samples making the selection process potentially unstable. This suggests the application of a two-level hierarchical Bayesian probit regression model for variable selection which assumes a prior that favours sparseness. The classification performance of this method is shown to improve that of the Probabilistic K-Nearest Neighbour model
Bayesian nonparametric models for peak identification in MALDI-TOF mass spectroscopy
We present a novel nonparametric Bayesian approach based on L\'{e}vy Adaptive
Regression Kernels (LARK) to model spectral data arising from MALDI-TOF (Matrix
Assisted Laser Desorption Ionization Time-of-Flight) mass spectrometry. This
model-based approach provides identification and quantification of proteins
through model parameters that are directly interpretable as the number of
proteins, mass and abundance of proteins and peak resolution, while having the
ability to adapt to unknown smoothness as in wavelet based methods. Informative
prior distributions on resolution are key to distinguishing true peaks from
background noise and resolving broad peaks into individual peaks for multiple
protein species. Posterior distributions are obtained using a reversible jump
Markov chain Monte Carlo algorithm and provide inference about the number of
peaks (proteins), their masses and abundance. We show through simulation
studies that the procedure has desirable true-positive and false-discovery
rates. Finally, we illustrate the method on five example spectra: a blank
spectrum, a spectrum with only the matrix of a low-molecular-weight substance
used to embed target proteins, a spectrum with known proteins, and a single
spectrum and average of ten spectra from an individual lung cancer patient.Comment: Published in at http://dx.doi.org/10.1214/10-AOAS450 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Feature Selection and Dimensionality Reduction in Genomics and Proteomics
International audienceFinding reliable, meaningful patterns in data with high numbers of attributes can be extremely difficult. Feature selection helps us to decide what attributes or combination of attributes are most important for finding these patterns. In this chapter, we study feature selection methods for building classification models from high-throughput genomic (microarray) and proteomic (mass spectrometry) data sets. Thousands of feature candidates must be analyzed, compared and combined in such data sets. We describe the basics of four different approaches used for feature selection and illustrate their effects on an MS cancer proteomic data set. The closing discussion provides assistance in performing an analysis in high-dimensional genomic and proteomic data
Peaks detection and alignment for mass spectrometry data
The goal of this paper is to review existing methods for protein mass spectrometry data analysis, and to present a new methodology for automatic extraction of significant peaks (biomarkers). For the pre-processing step required for data from MALDI-TOF or SELDI- TOF spectra, we use a purely nonparametric approach that combines stationary invariant wavelet transform for noise removal and penalized spline quantile regression for baseline correction. We further present a multi-scale spectra alignment technique that is based on identification of statistically significant peaks from a set of spectra. This method allows one to find common peaks in a set of spectra that can subsequently be mapped to individual proteins. This may serve as useful biomarkers in medical applications, or as individual features for further multidimensional statistical analysis. MALDI-TOF spectra obtained from serum samples are used throughout the paper to illustrate the methodology
Latent protein trees
Unbiased, label-free proteomics is becoming a powerful technique for
measuring protein expression in almost any biological sample. The output of
these measurements after preprocessing is a collection of features and their
associated intensities for each sample. Subsets of features within the data are
from the same peptide, subsets of peptides are from the same protein, and
subsets of proteins are in the same biological pathways, therefore, there is
the potential for very complex and informative correlational structure inherent
in these data. Recent attempts to utilize this data often focus on the
identification of single features that are associated with a particular
phenotype that is relevant to the experiment. However, to date, there have been
no published approaches that directly model what we know to be multiple
different levels of correlation structure. Here we present a hierarchical
Bayesian model which is specifically designed to model such correlation
structure in unbiased, label-free proteomics. This model utilizes partial
identification information from peptide sequencing and database lookup as well
as the observed correlation in the data to appropriately compress features into
latent proteins and to estimate their correlation structure. We demonstrate the
effectiveness of the model using artificial/benchmark data and in the context
of a series of proteomics measurements of blood plasma from a collection of
volunteers who were infected with two different strains of viral influenza.Comment: Published in at http://dx.doi.org/10.1214/13-AOAS639 the Annals of
Applied Statistics (http://www.imstat.org/aoas/) by the Institute of
Mathematical Statistics (http://www.imstat.org
Machine learning applications in proteomics research: How the past can boost the future
Machine learning is a subdiscipline within artificial intelligence that focuses on algorithms that allow computers to learn solving a (complex) problem from existing data. This ability can be used to generate a solution to a particularly intractable problem, given that enough data are available to train and subsequently evaluate an algorithm on. Since MS-based proteomics has no shortage of complex problems, and since publicly available data are becoming available in ever growing amounts, machine learning is fast becoming a very popular tool in the field. We here therefore present an overview of the different applications of machine learning in proteomics that together cover nearly the entire wet- and dry-lab workflow, and that address key bottlenecks in experiment planning and design, as well as in data processing and analysis.acceptedVersio
Inferential stability in systems biology
The modern biological sciences are fraught with statistical difficulties. Biomolecular
stochasticity, experimental noise, and the “large p, small n” problem all contribute to
the challenge of data analysis. Nevertheless, we routinely seek to draw robust, meaningful
conclusions from observations. In this thesis, we explore methods for assessing
the effects of data variability upon downstream inference, in an attempt to quantify and
promote the stability of the inferences we make.
We start with a review of existing methods for addressing this problem, focusing upon the
bootstrap and similar methods. The key requirement for all such approaches is a statistical
model that approximates the data generating process.
We move on to consider biomarker discovery problems. We present a novel algorithm for
proposing putative biomarkers on the strength of both their predictive ability and the stability
with which they are selected. In a simulation study, we find our approach to perform
favourably in comparison to strategies that select on the basis of predictive performance
alone.
We then consider the real problem of identifying protein peak biomarkers for HAM/TSP,
an inflammatory condition of the central nervous system caused by HTLV-1 infection.
We apply our algorithm to a set of SELDI mass spectral data, and identify a number of
putative biomarkers. Additional experimental work, together with known results from the
literature, provides corroborating evidence for the validity of these putative biomarkers.
Having focused on static observations, we then make the natural progression to time
course data sets. We propose a (Bayesian) bootstrap approach for such data, and then
apply our method in the context of gene network inference and the estimation of parameters
in ordinary differential equation models. We find that the inferred gene networks
are relatively unstable, and demonstrate the importance of finding distributions of ODE
parameter estimates, rather than single point estimates
Censored Data Regression in High-Dimension and Low-Sample Size Settings For Genomic Applications
New high-throughput technologies are generating various types of high-dimensional genomic and proteomic data and meta-data (e.g., networks and pathways) in order to obtain a systems-level understanding of various complex diseases such as human cancers and cardiovascular diseases. As the amount and complexity of the data increase and as the questions being addressed become more sophisticated, we face the great challenge of how to model such data in order to draw valid statistical and biological conclusions. One important problem in genomic research is to relate these high-throughput genomic data to various clinical outcomes, including possibly censored survival outcomes such as age at disease onset or time to cancer recurrence. We review some recently developed methods for censored data regression in the high-dimension and low-sample size setting, with emphasis on applications to genomic data. These methods include dimension reduction-based methods, regularized estimation methods such as Lasso and threshold gradient descent method, gradient descent boosting methods and nonparametric pathways-based regression models. These methods are demonstrated and compared by analysis of a data set of microarray gene expression profiles of 240 patients with diffuse large B-cell lymphoma together with follow-up survival information. Areas of further research are also presented
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