Mutual information between discrete and continuous data sets.
Ontology highlight
ABSTRACT:
SUBMITTER: Ross BC
PROVIDER: S-EPMC3929353 | biostudies-literature | 2014
REPOSITORIES: biostudies-literature
Publications
Mutual information (MI) is a powerful method for detecting relationships between data sets. There are accurate methods for estimating MI that avoid problems with "binning" when both data sets are discrete or when both data sets are continuous. We present an accurate, non-binning MI estimator for the case of one discrete data set and one continuous data set. This case applies when measuring, for example, the relationship between base sequence and gene expression level, or the effect of a cancer d ...[more]
Similar Datasets
Project description:Mutual information, a general measure of the relatedness between two random variables, has been actively used in the analysis of biomedical data. The mutual information between two discrete variables is conventionally calculated by their joint probabilities estimated from the frequency of observed samples in each combination of variable categories. However, this conventional approach is no longer efficient for discrete variables with many categories, which can be easily found in large-scale biomedical data such as diagnosis codes, drug compounds, and genotypes. Here, we propose a method to provide stable estimations for the mutual information between discrete variables with many categories. Simulation studies showed that the proposed method reduced the estimation errors by 45 folds and improved the correlation coefficients with true values by 99 folds, compared with the conventional calculation of mutual information. The proposed method was also demonstrated through a case study for diagnostic data in electronic health records. This method is expected to be useful in the analysis of various biomedical data with discrete variables.
| S-EPMC4456943 | biostudies-literature
Project description:BackgroundA long noncoding RNA (lncRNA) can act as a competing endogenous RNA (ceRNA) to compete with an mRNA for binding to the same miRNA. Such an interplay between the lncRNA, miRNA, and mRNA is called a ceRNA crosstalk. As an miRNA may have multiple lncRNA targets and multiple mRNA targets, connecting all the ceRNA crosstalks mediated by the same miRNA forms a ceRNA network. Methods have been developed to construct ceRNA networks in the literature. However, these methods have limits because they have not explored the expression characteristics of total RNAs.ResultsWe proposed a novel method for constructing ceRNA networks and applied it to a paired RNA-seq data set. The first step of the method takes a competition regulation mechanism to derive candidate ceRNA crosstalks. Second, the method combines a competition rule and pointwise mutual information to compute a competition score for each candidate ceRNA crosstalk. Then, ceRNA crosstalks which have significant competition scores are selected to construct the ceRNA network. The key idea, pointwise mutual information, is ideally suitable for measuring the complex point-to-point relationships embedded in the ceRNA networks.ConclusionComputational experiments and results demonstrate that the ceRNA networks can capture important regulatory mechanism of breast cancer, and have also revealed new insights into the treatment of breast cancer. The proposed method can be directly applied to other RNA-seq data sets for deeper disease understanding.
| S-EPMC6929403 | biostudies-literature
Project description:BackgroundProbability based statistical learning methods such as mutual information and Bayesian networks have emerged as a major category of tools for reverse engineering mechanistic relationships from quantitative biological data. In this work we introduce a new statistical learning strategy, MI3 that addresses three common issues in previous methods simultaneously: (1) handling of continuous variables, (2) detection of more complex three-way relationships and (3) better differentiation of causal versus confounding relationships. With these improvements, we provide a more realistic representation of the underlying biological system.ResultsWe test the MI3 algorithm using both synthetic and experimental data. In the synthetic data experiment, MI3 achieved an absolute sensitivity/precision of 0.77/0.83 and a relative sensitivity/precision both of 0.99. In addition, MI3 significantly outperformed the control methods, including Bayesian networks, classical two-way mutual information and a discrete version of MI3. We then used MI3 and control methods to infer a regulatory network centered at the MYC transcription factor from a published microarray dataset. Models selected by MI3 were numerically and biologically distinct from those selected by control methods. Unlike control methods, MI3 effectively differentiated true causal models from confounding models. MI3 recovered major MYC cofactors, and revealed major mechanisms involved in MYC dependent transcriptional regulation, which are strongly supported by literature. The MI3 network showed that limited sets of regulatory mechanisms are employed repeatedly to control the expression of large number of genes.ConclusionOverall, our work demonstrates that MI3 outperforms the frequently used control methods, and provides a powerful method for inferring mechanistic relationships underlying biological and other complex systems. The MI3 method is implemented in R in the "mi3" package, available under the GNU GPL from http://sysbio.engin.umich.edu/~luow/downloads.php and from the R package archive CRAN.
| S-EPMC2613931 | biostudies-literature
Project description:MotivationStudying the interaction or co-expression of the proteins or markers in the tumor microenvironment of cancer subjects can be crucial in the assessment of risks, such as death or recurrence. In the conventional approach, the cells need to be declared positive or negative for a marker based on its intensity. For multiple markers, manual thresholds are required for all the markers, which can become cumbersome. The performance of the subsequent analysis relies heavily on this step and thus suffers from subjectivity and lacks robustness.ResultsWe present a new method where different marker intensities are viewed as dependent random variables, and the mutual information (MI) between them is considered to be a metric of co-expression. Estimation of the joint density, as required in the traditional form of MI, becomes increasingly challenging as the number of markers increases. We consider an alternative formulation of MI which is conceptually similar but has an efficient estimation technique for which we develop a new generalization. With the proposed method, we analyzed a lung cancer dataset finding the co-expression of the markers, HLA-DR and CK to be associated with survival. We also analyzed a triple negative breast cancer dataset finding the co-expression of the immuno-regulatory proteins, PD1, PD-L1, Lag3 and IDO, to be associated with disease recurrence. We demonstrated the robustness of our method through different simulation studies.Availability and implementationThe associated R package can be found here, https://github.com/sealx017/MIAMI.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC9344855 | biostudies-literature
Project description:We describe a new residual for general regression models, defined as pr(Y* < y) - pr(Y* > y), where y is the observed outcome and Y* is a random variable from the fitted distribution. This probability-scale residual can be written as E {sign(y, Y*)} whereas the popular observed-minus-expected residual can be thought of as E(y - Y*). Therefore, the probability-scale residual is useful in settings where differences are not meaningful or where the expectation of the fitted distribution cannot be calculated. We present several desirable properties of the probability-scale residual that make it useful for diagnostics and measuring residual correlation, especially across different outcome types. We demonstrate its utility for continuous, ordered discrete, and censored outcomes, including current status data, and with various models including Cox regression, quantile regression, and ordinal cumulative probability models, for which fully specified distributions are not desirable or needed, and in some cases suitable residuals are not available. The residual is illustrated with simulated data and real datasets from HIV-infected patients on therapy in the southeastern United States and Latin America.
| S-EPMC5364820 | biostudies-literature
Project description:Record linkage of administrative and survey data is increasingly used to generate evidence to inform policy and services. Although a powerful and efficient way of generating new information from existing data sets, errors related to data processing before, during and after linkage can bias results. However, researchers and users of linked data rarely have access to information that can be used to assess these biases or take them into account in analyses. As linked administrative data are increasingly used to provide evidence to guide policy and services, linkage error, which disproportionately affects disadvantaged groups, can undermine evidence for public health. We convened a group of researchers and experts from government data providers to develop guidance about the information that needs to be made available about the data linkage process, by data providers, data linkers, analysts and the researchers who write reports. The guidance goes beyond recommendations for information to be included in research reports. Our aim is to raise awareness of information that may be required at each step of the linkage pathway to improve the transparency, reproducibility, and accuracy of linkage processes, and the validity of analyses and interpretation of results.
| S-EPMC5896589 | biostudies-literature
Project description:Systematic, high-throughput dissection of causal post-translational regulatory dependencies, on a genome wide basis, is still one of the great challenges of biology. Due to its complexity, however, only a handful of computational algorithms have been developed for this task. Here we present CINDy (Conditional Inference of Network Dynamics), a novel algorithm for the genome-wide, context specific inference of regulatory dependencies between signaling protein and transcription factor activity, from gene expression data. The algorithm uses a novel adaptive partitioning methodology to accurately estimate the full Condition Mutual Information (CMI) between a transcription factor and its targets, given the expression of a signaling protein. We show that CMI analysis is optimally suited to dissecting post-translational dependencies. Indeed, when tested against a gold standard dataset of experimentally validated protein-protein interactions in signal transduction networks, CINDy significantly outperforms previous methods, both in terms of sensitivity and precision.
| S-EPMC4196905 | biostudies-literature
Project description:MotivationDeep learning approaches have empowered single-cell omics data analysis in many ways and generated new insights from complex cellular systems. As there is an increasing need for single-cell omics data to be integrated across sources, types and features of data, the challenges of integrating single-cell omics data are rising. Here, we present an unsupervised deep learning algorithm that learns discriminative representations for single-cell data via maximizing mutual information, SMILE (Single-cell Mutual Information Learning).ResultsUsing a unique cell-pairing design, SMILE successfully integrates multisource single-cell transcriptome data, removing batch effects and projecting similar cell types, even from different tissues, into the shared space. SMILE can also integrate data from two or more modalities, such as joint-profiling technologies using single-cell ATAC-seq, RNA-seq, DNA methylation, Hi-C and ChIP data. When paired cells are known, SMILE can integrate data with unmatched feature, such as genes for RNA-seq and genome-wide peaks for ATAC-seq. Integrated representations learned from joint-profiling technologies can then be used as a framework for comparing independent single source data.Availability and implementationThe source code of SMILE including analyses of key results in the study can be found at: https://github.com/rpmccordlab/SMILE, implemented in Python.Supplementary informationSupplementary data are available at Bioinformatics online.
| S-EPMC10060712 | biostudies-literature
Project description:Coevolving residues in a multiple sequence alignment provide evolutionary clues of biophysical interactions in 3D structure. Despite a rich literature describing amino acid coevolution within or between proteins and nucleic acid coevolution within RNA, to date there has been no direct evidence of coevolution between protein and RNA. The ribosome, a structurally conserved macromolecular machine composed of over 50 interacting protein and RNA chains, provides a natural example of RNA/protein interactions that likely coevolved. We provide the first direct evidence of RNA/protein coevolution by characterizing the mutual information in residue triplets from a multiple sequence alignment of ribosomal protein L22 and neighboring 23S RNA. We define residue triplets as three positions in the multiple sequence alignment, where one position is from the 23S RNA and two positions are from the L22 protein. We show that residue triplets with high mutual information are more likely than residue doublets to be proximal in 3D space. Some high mutual information residue triplets cluster in a connected series across the L22 protein structure, similar to patterns seen in protein coevolution. We also describe RNA nucleotides for which switching from one nucleotide to another (or between purines and pyrimidines) results in a change in amino acid distribution for proximal amino acid positions. Multiple crystal structures for evolutionarily distinct ribosome species can provide structural evidence for these differences. For one residue triplet, a pyrimidine in one species is a purine in another, and RNA/protein hydrogen bonds are present in one species but not the other. The results provide the first direct evidence of RNA/protein coevolution by using higher order mutual information, suggesting that biophysical constraints on interacting RNA and protein chains are indeed a driving force in their evolution.
| S-EPMC3261191 | biostudies-literature
Project description:BackgroundAlthough microarray gene expression analysis has become popular, it remains difficult to interpret the biological changes caused by stimuli or variation of conditions. Clustering of genes and associating each group with biological functions are often used methods. However, such methods only detect partial changes within cell processes. Herein, we propose a method for discovering global changes within a cell by associating observed conditions of gene expression with gene functions.ResultsTo elucidate the association, we introduce a novel feature selection method called Least-Squares Mutual Information (LSMI), which computes mutual information without density estimaion, and therefore LSMI can detect nonlinear associations within a cell. We demonstrate the effectiveness of LSMI through comparison with existing methods. The results of the application to yeast microarray datasets reveal that non-natural stimuli affect various biological processes, whereas others are no significant relation to specific cell processes. Furthermore, we discover that biological processes can be categorized into four types according to the responses of various stimuli: DNA/RNA metabolism, gene expression, protein metabolism, and protein localization.ConclusionWe proposed a novel feature selection method called LSMI, and applied LSMI to mining the association between conditions of yeast and biological processes through microarray datasets. In fact, LSMI allows us to elucidate the global organization of cellular process control.
| S-EPMC2648797 | biostudies-literature