21,202 research outputs found
Differential gene expression graphs: A data structure for classification in DNA microarrays
This paper proposes an innovative data structure to be used as a backbone in designing microarray phenotype sample classifiers. The data structure is based on graphs and it is built from a differential analysis of the expression levels of healthy and diseased tissue samples in a microarray dataset. The proposed data structure is built in such a way that, by construction, it shows a number of properties that are perfectly suited to address several problems like feature extraction, clustering, and classificatio
Systems Biology and the Development of Vaccines and Drugs for Malaria Treatments
The sequencing race has ended and the functional race has already begun. Microarray technology enables
simultaneous gene expression analysis of thousands of genes, enabling a snapshot of an organismsā
transcriptome at an unprecedented resolution. The close correlation between gene transcription and
function, allow the inference of biological processes from the assessed transcriptome profile. Among the
sophisticated analytical problems in microarray technology at the front and back ends respectively, are the
selection of optimal DNA oligos and computational analysis of the genes expression. In this review paper,
we analyse important methods in use today in customized oligos design. In the course of executing this,
we discovered that the oligos designer algorithm hanged on gene PFA0135w of chromosome 1, while
designing oligos for the gene sequences of Plasmodium falciparum. We do not know the reason for this
yet, as the algorithm runs on other sequences like the yeast (Saccharomyces cervisiae) and Neurospora
crassa. We conclude the paper highlighting the procedures encompassing the back end phase and discuss
their application to the development of vaccines and drugs for malaria treatment. Note that, malaria is the
cause of significant global morbidity and mortality with 300-500 million cases annually. Our aims are not
ends, but a means to achieve the following: Iterate the need for experimental biologists to (i) know how to
design their customized oligos and (ii) have some idea about gene expression analysis and the need for
cooperation between experimental biologists and their counterpart, the computational biologists. These
will help experimental biologists to coordinate very well the front and the back ends of the system
biology analysis of the whole genome effectively
Experimental and computational applications of microarray technology for malaria eradication in Africa
Various mutation assisted drug resistance evolved in Plasmodium falciparum strains and insecticide
resistance to female Anopheles mosquito account for major biomedical catastrophes standing against
all efforts to eradicate malaria in Sub-Saharan Africa. Malaria is endemic in more than 100 countries and
by far the most costly disease in terms of human health causing major losses among many African
nations including Nigeria. The fight against malaria is failing and DNA microarray analysis need to keep
up the pace in order to unravel the evolving parasiteās gene expression profile which is a pointer to
monitoring the genes involved in malariaās infective metabolic pathway. Huge data is generated and
biologists have the challenge of extracting useful information from volumes of microarray data.
Expression levels for tens of thousands of genes can be simultaneously measured in a single
hybridization experiment and are collectively called a āgene expression profileā. Gene expression
profiles can also be used in studying various state of malaria development in which expression profiles
of different disease states at different time points are collected and compared to each other to establish
a classifying scheme for purposes such as diagnosis and treatments with adequate drugs. This paper
examines microarray technology and its application as supported by appropriate software tools from
experimental set-up to the level of data analysis. An assessment of the level of microarray technology
in Africa, its availability and techniques required for malaria eradication and effective healthcare in
Nigeria and Africa in general were also underscored
Physico-chemical foundations underpinning microarray and next-generation sequencing experiments
Hybridization of nucleic acids on solid surfaces is a key process involved in high-throughput technologies such as microarrays and, in some cases, next-generation sequencing (NGS). A physical understanding of the hybridization process helps to determine the accuracy of these technologies. The goal of a widespread research program is to develop reliable transformations between the raw signals reported by the technologies and individual molecular concentrations from an ensemble of nucleic acids. This research has inputs from many areas, from bioinformatics and biostatistics, to theoretical and experimental biochemistry and biophysics, to computer simulations. A group of leading researchers met in Ploen Germany in 2011 to discuss present knowledge and limitations of our physico-chemical understanding of high-throughput nucleic acid technologies. This meeting inspired us to write this summary, which provides an overview of the state-of-the-art approaches based on physico-chemical foundation to modeling of the nucleic acids hybridization process on solid surfaces. In addition, practical application of current knowledge is emphasized
Knowledge-based gene expression classification via matrix factorization
Motivation: Modern machine learning methods based on matrix decomposition techniques, like independent component analysis (ICA) or non-negative matrix factorization (NMF), provide new and efficient analysis tools which are currently explored to analyze gene expression profiles. These exploratory feature extraction techniques yield expression modes (ICA) or metagenes (NMF). These extracted features are considered indicative of underlying regulatory processes. They can as well be applied to the classification of gene expression datasets by grouping samples into different categories for diagnostic purposes or group genes into functional categories for further investigation of related metabolic pathways and regulatory networks.
Results: In this study we focus on unsupervised matrix factorization techniques and apply ICA and sparse NMF to microarray datasets. The latter monitor the gene expression levels of human peripheral blood cells during differentiation from monocytes to macrophages. We show that these tools are able to identify relevant signatures in the deduced component matrices and extract informative sets of marker genes from these gene expression profiles. The methods rely on the joint discriminative power of a set of marker genes rather than on single marker genes. With these sets of marker genes, corroborated by leave-one-out or random forest cross-validation, the datasets could easily be classified into related diagnostic categories. The latter correspond to either monocytes versus macrophages or healthy vs Niemann Pick C disease patients.Siemens AG, MunichDFG (Graduate College 638)DAAD (PPP Luso - AlemĖa and PPP Hispano - Alemanas
A cDNA Microarray Gene Expression Data Classifier for Clinical Diagnostics Based on Graph Theory
Despite great advances in discovering cancer molecular profiles, the proper application of microarray technology to routine clinical diagnostics is still a challenge. Current practices in the classification of microarrays' data show two main limitations: the reliability of the training data sets used to build the classifiers, and the classifiers' performances, especially when the sample to be classified does not belong to any of the available classes. In this case, state-of-the-art algorithms usually produce a high rate of false positives that, in real diagnostic applications, are unacceptable. To address this problem, this paper presents a new cDNA microarray data classification algorithm based on graph theory and is able to overcome most of the limitations of known classification methodologies. The classifier works by analyzing gene expression data organized in an innovative data structure based on graphs, where vertices correspond to genes and edges to gene expression relationships. To demonstrate the novelty of the proposed approach, the authors present an experimental performance comparison between the proposed classifier and several state-of-the-art classification algorithm
Effect of pooling samples on the efficiency of comparative studies using microarrays
Many biomedical experiments are carried out by pooling individual biological
samples. However, pooling samples can potentially hide biological variance and
give false confidence concerning the data significance. In the context of
microarray experiments for detecting differentially expressed genes, recent
publications have addressed the problem of the efficiency of sample-pooling,
and some approximate formulas were provided for the power and sample size
calculations. It is desirable to have exact formulas for these calculations and
have the approximate results checked against the exact ones. We show that the
difference between the approximate and exact results can be large. In this
study, we have characterized quantitatively the effect of pooling samples on
the efficiency of microarray experiments for the detection of differential gene
expression between two classes. We present exact formulas for calculating the
power of microarray experimental designs involving sample pooling and technical
replications. The formulas can be used to determine the total numbers of arrays
and biological subjects required in an experiment to achieve the desired power
at a given significance level. The conditions under which pooled design becomes
preferable to non-pooled design can then be derived given the unit cost
associated with a microarray and that with a biological subject. This paper
thus serves to provide guidance on sample pooling and cost effectiveness. The
formulation in this paper is outlined in the context of performing microarray
comparative studies, but its applicability is not limited to microarray
experiments. It is also applicable to a wide range of biomedical comparative
studies where sample pooling may be involved.Comment: 8 pages, 1 figure, 2 tables; to appear in Bioinformatic
A comparative analysis of existing oligonucleotides selection algorithms for microarray technology
In system biology, DNA microarray technology is an indispensable tool for the biological analysis
involved at the level of the whole genome. Among the sophisticated analytical problems in microarray
technology at the front and back ends, respectively, are the selection of optimal DNA oligonucleotides
(henceforth oligos) and computational analysis of the genes expression data. A computational
comparative analysis of the methods used to select oligos is important since the design and quality of
the microarray probes are of critical importance for the hybridization experiments as well as subsequent
analysis of the data. In an attempt to enhance efficient and effective design at the front end, a
computational comparative analysis was performed on oligos selection tools using the barley ESTs, as
well as the Saccharomyces cerevisiae, Encephalitozoon cuniculi and human genomes. The analysis also
shows that a large number of the existing tools are difficult to install and configure. For cross
hybridization test, most rely on BLAST and therefore design ill specific oligonucleotides. Furthermore,
most are non-intuitive to use and lack important oligo design and software features
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