Identifying latent structure in large data matrices is essential for exploring biological processes. Here, we consider recovering gene co-expression networks from gene expression data, where each network encodes relationships between genes that are locally co-regulated by shared biological mechanisms. To do this, we de…
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48 results for “gene regulation”
The adoption of deep learning techniques in genomics has been hindered by the difficulty of mechanistically interpreting the models that these techniques produce. In recent years, a variety of post-hoc attribution methods have been proposed for addressing this neural network interpretability problem in the context of g…
We present a Bayesian hierarchical multi-view mixture model termed Symphony that simultaneously learns clusters of cells representing cell types and their underlying gene regulatory networks by integrating data from two views: single-cell gene expression data and paired epigenetic data, which is informative of gene-gen…
Motivation: Cell-biological processes are regulated through a complex network of interactions between genes and their products. The processes, their activating conditions, and the associated transcriptional responses are often unknown. Organism-wide modeling of network activation can reveal unique and shared mechanisms…
Computational methods that predict differential gene expression from histone modification signals are highly desirable for understanding how histone modifications control the functional heterogeneity of cells through influencing differential gene regulation. Recent studies either failed to capture combinatorial effects…
Inferring the structure of gene regulatory networks (GRN) from gene expression data has many applications, from the elucidation of complex biological processes to the identification of potential drug targets. It is however a notoriously difficult problem, for which the many existing methods reach limited accuracy. In t…
GLasso: Regularized Multi-task Graphical Lasso for Joint Estimation of eQTL Mapping and Gene Networkstat.ML
A new method for joint eQTL mapping and gene network estimation.
problem Discovering SNP-gene relationships and gene-gene relationships in gene expression regulation.
method L1-2 regularized multi-task graphical lasso (L1-2 GLasso).
result Competitive performance on capturing true sparse structures of eQTL mapping and gene network.
Switched latent force models for reverse-engineering transcriptional regulation in gene expression dataphysics.bio-ph
To survive environmental conditions, cells transcribe their response activities into encoded mRNA sequences in order to produce certain amounts of protein concentrations. The external conditions are mapped into the cell through the activation of special proteins called transcription factors (TFs). Due to the difficult …
Proposes a novel network-based neighborhood regression for biological systems.
problem Lack of comprehensive analysis on biological modules using both global and local network data.
method Develops a community-wise least square optimization approach to analyze gene modules and their regulatory strength.
result Achieves exact minimax optimality and linear consistency in identifying gene module associations.
New method infers causal factors from large-scale data without full graph reconstruction.
problem Inferring causal variables from large-scale systems without full causal graph reconstruction.
method Supervised learning on simulated data using a neural network and subsampled-ensemble inference.
result Efficiently identifies causal relationships in large-scale gene regulatory networks.
Coregulation of the expression of groups of genes has been extensively demonstrated empirically in bacterial and eukaryotic systems. Such coregulation can arise through the use of shared regulatory motifs, which allow the coordinated expression of modules (and module groups) of functionally related genes across the gen…
Due to the dynamic nature of biological systems, biological networks underlying temporal process such as the development of {\it Drosophila melanogaster} can exhibit significant topological changes to facilitate dynamic regulatory functions. Thus it is essential to develop methodologies that capture the temporal evolut…
ASCEND discovers causal relationships in multi-omics data by leveraging known hierarchical structure.
problem Causal inference in high-dimensional multi-omics data, especially when ignoring the hierarchical structure.
method Two-tiered divide-and-conquer strategy with ancestral conditioning sets.
result Achieves polynomial-time complexity and accurately recovers ancestral relationships.
Components of biological systems interact with each other in order to carry out vital cell functions. Such information can be used to improve estimation and inference, and to obtain better insights into the underlying cellular mechanisms. Discovering regulatory interactions among genes is therefore an important problem…
Physically-Inspired Gaussian Process Models for Post-Transcriptional Regulation in Drosophilastat.ML
The regulatory process of Drosophila is thoroughly studied for understanding a great variety of biological principles. While pattern-forming gene networks are analysed in the transcription step, post-transcriptional events (e.g. translation, protein processing) play an important role in establishing protein expression …
Reproducing kernel Hilbert space based estimation of systems of ordinary differential equationsstat.ME
Non-linear systems of differential equations have attracted the interest in fields like system biology, ecology or biochemistry, due to their flexibility and their ability to describe dynamical systems. Despite the importance of such models in many branches of science they have not been the focus of systematic statisti…
We propose a family of statistical models for social network evolution over time, which represents an extension of Exponential Random Graph Models (ERGMs). Many of the methods for ERGMs are readily adapted for these models, including maximum likelihood estimation algorithms. We discuss models of this type and their pro…
With different genomes available, unsupervised learning algorithms are essential in learning genome-wide biological insights. Especially, the functional characterization of different genomes is essential for us to understand lives. In this book chapter, we review the state-of-the-art unsupervised learning algorithms fo…
RIDS: Robust Identification of Sparse Gene Regulatory Networks from Perturbation Experimentsq-bio.QM
Reconstructing the causal network in a complex dynamical system plays a crucial role in many applications, from sub-cellular biology to economic systems. Here we focus on inferring gene regulation networks (GRNs) from perturbation or gene deletion experiments. Despite their scientific merit, such perturbation experimen…
This Perspective provides examples of current and future applications of deep learning in pharmacogenomics, including: (1) identification of novel regulatory variants located in noncoding domains and their function as applied to pharmacoepigenomics; (2) patient stratification from medical records; and (3) prediction of…
A new method uses gene interaction networks to predict gene functions.
problem Predicting gene functions from gene interactions.
method Context graph kernel approach in a machine learning framework.
result The proposed method outperforms linkage-assumption-based methods.
VEGN uses graph neural networks to predict disease-causing mutations from genetic variants.
problem Identifying disease-causing mutations from millions of genetic variants.
method VEGN employs a graph neural network on a heterogeneous graph of genes and variants, learning gene-gene interactions.
result VEGN outperforms existing state-of-the-art models in variant effect prediction.
Bioinformatics tools have been developed to interpret gene expression data at the gene set level, and these gene set based analyses improve the biologists' capability to discover functional relevance of their experiment design. While elucidating gene set individually, inter gene sets association is rarely taken into co…
Identifying significant subsets of the genes, gene shaving is an essential and challenging issue for biomedical research for a huge number of genes and the complex nature of biological networks,. Since positive definite kernel based methods on genomic information can improve the prediction of diseases, in this paper we…
New method expands seed genes to functionally related clusters.
problem Discovering functionally related genes lacking GO terms.
method Semi-supervised learning with positive and unlabeled examples.
result LPU approaches significantly outperform existing methods.
New method handles correlated genes for better genomic prediction.
problem Technical issues with highly correlated genes in prediction models.
method Grouping algorithm that treats correlated genes as a group and uses their common patterns.
result Significantly outperforms standard models in prediction and feature selection.
Popular online enrichment analysis tools from the field of molecular systems biology provide users with the ability to submit their experimental results as gene sets for individual analysis. Such queries are kept private, and have never before been considered as a resource for integrative analysis. By harnessing gene s…
Elucidating the genetic basis of human diseases is a central goal of genetics and molecular biology. While traditional linkage analysis and modern high-throughput techniques often provide long lists of tens or hundreds of disease gene candidates, the identification of disease genes among the candidates remains time-con…
We present the extention and application of a new unsupervised statistical learning technique--the Partition Decoupling Method--to gene expression data. Because it has the ability to reveal non-linear and non-convex geometries present in the data, the PDM is an improvement over typical gene expression analysis algorith…
A novel method selects genes for high-dimensional gene expression data with class imbalance.
problem Class imbalance in gene expression datasets.
method Synthetic data balancing, greedy search, weighted robust score.
result The proposed method outperforms existing feature selection procedures.
Towards Probabilistic Generative Models Harnessing Graph Neural Networks for Disease-Gene Predictioncs.LG
Disease-gene prediction (DGP) refers to the computational challenge of predicting associations between genes and diseases. Effective solutions to the DGP problem have the potential to accelerate the therapeutic development pipeline at early stages via efficient prioritization of candidate genes for various diseases. In…
The problem of multilabel classification when the labels are related through a hierarchical categorization scheme occurs in many application domains such as computational biology. For example, this problem arises naturally when trying to automatically assign gene function using a controlled vocabularies like Gene Ontol…
The method integrates survival constraints into NMF for identifying survival-associated gene clusters.
problem Understanding and interpreting high-dimensional biological data for disease markers.
method Cox proportional hazards regression integrated with NMF via proportional hazards non-negative matrix factorization.
result The method can uncover survival-associated gene clusters in cancer gene expression data.
Genomics has revolutionized biology, enabling the interrogation of whole transcriptomes, genome-wide binding sites for proteins, and many other molecular processes. However, individual genomic assays measure elements that interact in vivo as components of larger molecular machines. Understanding how these high-order in…
When searching for gene pathways leading to specific disease outcomes, additional information on gene characteristics is often available that may facilitate to differentiate genes related to the disease from irrelevant background when connections involving both types of genes are observed and their relationships to the…
New methods detect continuous variation in single-cell data.
problem Continuous variation within and between cell types not detected by discrete analyses.
method Three topologically motivated mathematical methods for unsupervised feature selection.
result Detect additional biologically meaningful genes with coherent expression patterns.
Biogeography-Based Informative Gene Selection and Cancer Classification Using SVM and Random Forestscs.NE
Microarray cancer gene expression data comprise of very high dimensions. Reducing the dimensions helps in improving the overall analysis and classification performance. We propose two hybrid techniques, Biogeography - based Optimization - Random Forests (BBO - RF) and BBO - SVM (Support Vector Machines) with gene ranki…
RNA-binding proteins (RBPs) play crucial roles in many biological processes, e.g. gene regulation. Computational identification of RBP binding sites on RNAs are urgently needed. In particular, RBPs bind to RNAs by recognizing sequence motifs. Thus, fast locating those motifs on RNA sequences is crucial and time-efficie…
New gene selection method improves tumor classification accuracy.
problem Efficiently selecting relevant genes from high-dimensional tumor gene expression data.
method Fuzzy-Rough Set Theory for feature dependency analysis.
result The proposed method outperforms state-of-the-art techniques in tumor classification.
Various approaches to gene selection for cancer classification based on microarray data can be found in the literature and they may be grouped into two categories: univariate methods and multivariate methods. Univariate methods look at each gene in the data in isolation from others. They measure the contribution of a p…
New model generates realistic single-cell gene expression data.
problem Generating realistic single-cell gene expression profiles is challenging.
method scLDM, a latent diffusion model using Diffusion Transformers and linear interpolants.
result Superior performance in generating realistic single-cell gene expression data.
We address the problem of synthetic gene design using Bayesian optimization. The main issue when designing a gene is that the design space is defined in terms of long strings of characters of different lengths, which renders the optimization intractable. We propose a three-step approach to deal with this issue. First, …
Predicting the response of cancer cells to drugs is an important problem in pharmacogenomics. Recent efforts in generation of large scale datasets profiling gene expression and drug sensitivity in cell lines have provided a unique opportunity to study this problem. However, one major challenge is the small number of sa…
InfoSEM: A Deep Generative Model with Informative Priors for Gene Regulatory Network Inferencestat.ML
InfoSEM infers gene regulatory networks without GT labels, improving performance.
problem Inferring GRNs from gene expression data with high accuracy and avoiding biases.
method InfoSEM uses deep generative models with informative priors (textual gene embeddings).
result InfoSEM outperforms existing models by 38.5% across four datasets.
Diffusion Generative Modeling for Spatially Resolved Gene Expression Inference from Histology Imagescs.CV
Stem uses diffusion models to infer gene expression from H&E images.
problem Inference of gene expression from H&E stained images is time-consuming and expensive.
method Conditional diffusion generative model to infer gene expression.
result Stem achieves state-of-the-art performance in spatial gene expression prediction.
Unified framework improves gene prioritization in disease studies.
problem Identifying genes involved in diseases using heterogeneous biological data.
method Network propagation-based gene prioritization with integrated biological information.
result Significant improvements in prioritizing genes not identified by traditional methods.
In most gene expression data, the number of training samples is very small compared to the large number of genes involved in the experiments. However, among the large amount of genes, only a small fraction is effective for performing a certain task. Furthermore, a small subset of genes is desirable in developing gene e…
Most network-based protein (or gene) function prediction methods are based on the assumption that the labels of two adjacent proteins in the network are likely to be the same. However, assuming the pairwise relationship between proteins or genes is not complete, the information a group of genes that show very similar p…