2,022 research outputs found
Diagnostic prediction of complex diseases using phase-only correlation based on virtual sample template
Motivation: Complex diseases induce perturbations to interaction and regulation networks in living systems, resulting in dynamic equilibrium states that differ for different diseases and also normal states. Thus identifying gene expression patterns corresponding to different equilibrium states is of great benefit to the diagnosis and treatment of complex diseases. However, it remains a major challenge to deal with the high dimensionality and small size of available complex disease gene expression datasets currently used for discovering gene expression patterns.
Results: Here we present a phase-only correlation (POC) based classification method for recognizing the type of complex diseases. First, a virtual sample template is constructed for each subclass by averaging all samples of each subclass in a training dataset. Then the label of a test sample is determined by measuring the similarity between the test sample and each template. This novel method can detect the similarity of overall patterns emerged from the differentially expressed genes or proteins while ignoring small mismatches.
Conclusions: The experimental results obtained on seven publicly available complex disease datasets including microarray and protein array data demonstrate that the proposed POC-based disease classification method is effective and robust for diagnosing complex diseases with regard to the number of initially selected features, and its recognition accuracy is better than or comparable to other state-of-the-art machine learning methods. In addition, the proposed method does not require parameter tuning and data scaling, which can effectively reduce the occurrence of over-fitting and bias
Exploring Patterns of Epigenetic Information With Data Mining Techniques
[Abstract] Data mining, a part of the Knowledge Discovery in Databases process (KDD), is the process of extracting patterns from large data sets by combining methods from statistics and artificial intelligence with database management. Analyses of epigenetic data have evolved towards genome-wide and high-throughput approaches, thus generating great amounts of data for which data mining is essential. Part of these data may contain patterns of epigenetic information which are mitotically and/or meiotically heritable determining gene expression and cellular differentiation, as well as cellular fate. Epigenetic lesions and genetic mutations are acquired by individuals during their life and accumulate with ageing. Both defects, either together or individually, can result in losing control over cell growth and, thus, causing cancer development. Data mining techniques could be then used to extract the previous patterns. This work reviews some of the most important applications of data mining to epigenetics.Programa Iberoamericano de Ciencia y Tecnología para el Desarrollo; 209RT-0366Galicia. Consellería de Economía e Industria; 10SIN105004PRInstituto de Salud Carlos III; RD07/0067/000
High-dimensional classification using features annealed independence rules
Classification using high-dimensional features arises frequently in many
contemporary statistical studies such as tumor classification using microarray
or other high-throughput data. The impact of dimensionality on classifications
is poorly understood. In a seminal paper, Bickel and Levina [Bernoulli 10
(2004) 989--1010] show that the Fisher discriminant performs poorly due to
diverging spectra and they propose to use the independence rule to overcome the
problem. We first demonstrate that even for the independence classification
rule, classification using all the features can be as poor as the random
guessing due to noise accumulation in estimating population centroids in
high-dimensional feature space. In fact, we demonstrate further that almost all
linear discriminants can perform as poorly as the random guessing. Thus, it is
important to select a subset of important features for high-dimensional
classification, resulting in Features Annealed Independence Rules (FAIR). The
conditions under which all the important features can be selected by the
two-sample -statistic are established. The choice of the optimal number of
features, or equivalently, the threshold value of the test statistics are
proposed based on an upper bound of the classification error. Simulation
studies and real data analysis support our theoretical results and demonstrate
convincingly the advantage of our new classification procedure.Comment: Published in at http://dx.doi.org/10.1214/07-AOS504 the Annals of
Statistics (http://www.imstat.org/aos/) by the Institute of Mathematical
Statistics (http://www.imstat.org
The Transcriptome of SH-SY5Y at Single-Cell Resolution: A CITE-Seq Data Analysis Workflow
Cellular Indexing of Transcriptomes and Epitopes by Sequencing (CITE-seq) is a recently established multimodal single cell analysis technique combining the immunophenotyping capabilities of antibody labeling and cell sorting with the resolution of single-cell RNA sequencing (scRNA-seq). By simply adding a 12-bp nucleotide barcode to antibodies (cell hashing), CITE-seq can be used to sequence antibody-bound tags alongside the cellular mRNA, thus reducing costs of scRNA-seq by performing it at the same time on multiple barcoded samples in a single run. Here, we illustrate an ideal CITE-seq data analysis workflow by characterizing the transcriptome of SH-SY5Y neuroblastoma cell line, a widely used model to study neuronal function and differentiation. We obtained transcriptomes from a total of 2879 single cells, measuring an average of 1600 genes/cell. Along with standard scRNA-seq data handling procedures, such as quality checks and cell filtering procedures, we performed exploratory analyses to identify most stable genes to be possibly used as reference housekeeping genes in qPCR experiments. We also illustrate how to use some popular R packages to investigate cell heterogeneity in scRNA-seq data, namely Seurat, Monocle, and slalom. Both the CITE-seq dataset and the code used to analyze it are freely shared and fully reusable for future research
Clustering of the SOM easily reveals distinct gene expression patterns: results of a reanalysis of lymphoma study
BACKGROUND: A method to evaluate and analyze the massive data generated by series of microarray experiments is of utmost importance to reveal the hidden patterns of gene expression. Because of the complexity and the high dimensionality of microarray gene expression profiles, the dimensional reduction of raw expression data and the feature selections necessary for, for example, classification of disease samples remains a challenge. To solve the problem we propose a two-level analysis. First self-organizing map (SOM) is used. SOM is a vector quantization method that simplifies and reduces the dimensionality of original measurements and visualizes individual tumor sample in a SOM component plane. Next, hierarchical clustering and K-means clustering is used to identify patterns of gene expression useful for classification of samples. RESULTS: We tested the two-level analysis on public data from diffuse large B-cell lymphomas. The analysis easily distinguished major gene expression patterns without the need for supervision: a germinal center-related, a proliferation, an inflammatory and a plasma cell differentiation-related gene expression pattern. The first three patterns matched the patterns described in the original publication using supervised clustering analysis, whereas the fourth one was novel. CONCLUSIONS: Our study shows that by using SOM as an intermediate step to analyze genome-wide gene expression data, the gene expression patterns can more easily be revealed. The "expression display" by the SOM component plane summarises the complicated data in a way that allows the clinician to evaluate the classification options rather than giving a fixed diagnosis
Expression cartography of human tissues using self organizing maps
Background: The availability of parallel, high-throughput microarray and sequencing experiments poses a challenge how to best arrange and to analyze the obtained heap of multidimensional data in a concerted way. Self organizing maps (SOM), a machine learning method, enables the parallel sample- and gene-centered view on the data combined with strong visualization and second-level analysis capabilities. The paper addresses aspects of the method with practical impact in the context of expression analysis of complex data sets.
Results: The method was applied to generate a SOM characterizing the whole genome expression profiles of 67 healthy human tissues selected from ten tissue categories (adipose, endocrine, homeostasis, digestion, exocrine, epithelium, sexual reproduction, muscle, immune system and nervous tissues). SOM mapping reduces the dimension of expression data from ten thousands of genes to a few thousands of metagenes where each metagene acts as representative of a minicluster of co-regulated single genes. Tissue-specific and common properties shared between groups of tissues emerge as a handful of localized spots in the tissue maps collecting groups of co-regulated and co-expressed metagenes. The functional context of the spots was discovered using overrepresentation analysis with respect to pre-defined gene sets of known functional impact. We found that tissue related spots typically contain enriched populations of gene sets well corresponding to molecular processes in the respective tissues. Analysis techniques normally used at the gene-level such as two-way hierarchical clustering provide a better signal-to-noise ratio and a better representativeness of the method if applied to the metagenes. Metagene-based clustering analyses aggregate the tissues into essentially three clusters containing nervous, immune system and the remaining tissues. 
Conclusions: The global view on the behavior of a few well-defined modules of correlated and differentially expressed genes is more intuitive and more informative than the separate discovery of the expression levels of hundreds or thousands of individual genes. The metagene approach is less sensitive to a priori selection of genes. It can detect a coordinated expression pattern whose components would not pass single-gene significance thresholds and it is able to extract context-dependent patterns of gene expression in complex data sets.

Decomposing feature-level variation with Covariate Gaussian Process Latent Variable Models
The interpretation of complex high-dimensional data typically requires the
use of dimensionality reduction techniques to extract explanatory
low-dimensional representations. However, in many real-world problems these
representations may not be sufficient to aid interpretation on their own, and
it would be desirable to interpret the model in terms of the original features
themselves. Our goal is to characterise how feature-level variation depends on
latent low-dimensional representations, external covariates, and non-linear
interactions between the two. In this paper, we propose to achieve this through
a structured kernel decomposition in a hybrid Gaussian Process model which we
call the Covariate Gaussian Process Latent Variable Model (c-GPLVM). We
demonstrate the utility of our model on simulated examples and applications in
disease progression modelling from high-dimensional gene expression data in the
presence of additional phenotypes. In each setting we show how the c-GPLVM can
extract low-dimensional structures from high-dimensional data sets whilst
allowing a breakdown of feature-level variability that is not present in other
commonly used dimensionality reduction approaches
Integrated Multi-omics Analysis Using Variational Autoencoders: Application to Pan-cancer Classification
Different aspects of a clinical sample can be revealed by multiple types of
omics data. Integrated analysis of multi-omics data provides a comprehensive
view of patients, which has the potential to facilitate more accurate clinical
decision making. However, omics data are normally high dimensional with large
number of molecular features and relatively small number of available samples
with clinical labels. The "dimensionality curse" makes it challenging to train
a machine learning model using high dimensional omics data like DNA methylation
and gene expression profiles. Here we propose an end-to-end deep learning model
called OmiVAE to extract low dimensional features and classify samples from
multi-omics data. OmiVAE combines the basic structure of variational
autoencoders with a classification network to achieve task-oriented feature
extraction and multi-class classification. The training procedure of OmiVAE is
comprised of an unsupervised phase without the classifier and a supervised
phase with the classifier. During the unsupervised phase, a hierarchical
cluster structure of samples can be automatically formed without the need for
labels. And in the supervised phase, OmiVAE achieved an average classification
accuracy of 97.49% after 10-fold cross-validation among 33 tumour types and
normal samples, which shows better performance than other existing methods. The
OmiVAE model learned from multi-omics data outperformed that using only one
type of omics data, which indicates that the complementary information from
different omics datatypes provides useful insights for biomedical tasks like
cancer classification.Comment: 7 pages, 4 figure
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