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Georgy Meshcheryakov

Publications and source records attributed to Georgy Meshcheryakov.

4 recordsLinked to original sources

Exact computation of posterior distribution of mixture weights in hierarchical Bayesian models

Hierarchical mixture models are a powerful tool for modeling data generated from heterogeneous sources, particularly when the mixing proportion $\boldsymbol{w}$ itself is treated as a random variable with a Dirichlet or Beta-Liouville prior. Such models are widely employed in scenarios where uncertainty in class membership or data-generating processes must be probabilistically quantified. This paper studies the exact marginalization of the mixture weight. For the two-component case we give an $O(n^2)$ dynamic program -- and an $O(n \log^2 n)$ FFT variant -- for the marginal likelihood, and show that the exact posterior of the weight is a finite mixture of Beta distributions, delivering closed-form posterior summaries, credible intervals and per-observation local false-discovery rates without any sampling. For $K \ge 3$ components we give an exact joint dynamic program. The gain is largest in the small-sample regime the method is built for: on a real multilevel meta-analysis, a pathway-level dysregulation analysis of leukemia gene expression, and a leukemia-derived gene-panel benchmark with known ground truth, the exact interval for the signal proportion is calibrated where EM gives no interval at all (collapsing to a boundary) and Gaussian/Laplace approximations mis-cover, and it is two orders of magnitude faster than the sampler that would match it. On the large prostate-cancer benchmark, where every method has ample data, it agrees with locfdr on the gene ranking while adding a posterior interval for the null proportion.

stat.ME

MARADONER: Motif Activity Response Analysis Done Right

Inferring the activities of transcription factors from high-throughput transcriptomic or open chromatin profiling, such as RNA-/CAGE-/ATAC-Seq, is a long-standing challenge in systems biology. Identification of highly active master regulators enables mechanistic interpretation of differential gene expression, chromatin state changes, or perturbation responses across conditions, cell types, and diseases. Here, we describe MARADONER, a statistical framework and its software implementation for motif activity response analysis (MARA), utilizing the sequence-level features obtained with pattern matching (motif scanning) of individual promoters and promoter- or gene-level activity or expression estimates. Compared to the classic MARA, MARADONER (MARA-done-right) employs an unbiased variance parameter estimation and a bias-adjusted likelihood estimation of fixed effects, thereby enhancing goodness-of-fit and the accuracy of activity estimation. Further, MARADONER is capable of accounting for heteroscedasticity of motif scores and activity estimates.

stat.CO

MIXALIME: MIXture models for ALlelic IMbalance Estimation in high-throughput sequencing data

Modern high-throughput sequencing assays efficiently capture not only gene expression and different levels of gene regulation but also a multitude of genome variants. Focused analysis of alternative alleles of variable sites at homologous chromosomes of the human genome reveals allele-specific gene expression and allele-specific gene regulation by assessing allelic imbalance of read counts at individual sites. Here we formally describe an advanced statistical framework for detecting the allelic imbalance in allelic read counts at single-nucleotide variants detected in diverse omics studies (ChIP-Seq, ATAC-Seq, DNase-Seq, CAGE-Seq, and others). MIXALIME accounts for copy-number variants and aneuploidy, reference read mapping bias, and provides several scoring models to balance between sensitivity and specificity when scoring data with varying levels of experimental noise-caused overdispersion.

stat.AP

semopy 2: A Structural Equation Modeling Package with Random Effects in Python

Structural Equation Modeling (SEM) is an umbrella term that includes numerous multivariate statistical techniques that are employed throughout a plethora of research areas, ranging from social to natural sciences. Until recently, SEM software was either commercial or restricted to niche languages, and the lack of SEM packages compatible with more mainstream programming languages was dire. To combat that, we introduced a Python package semopy 1 that surpassed other state-of-the-art software in terms of performance and estimation accuracy. Yet, it was lacking in functionality and its usage was burdened with unnecessary boilerplate code. Here, we introduce a complete overhaul of semopy that improves upon the previous results and comes with lots of new capabilities. Furthermore, we propose a novel SEM model that combines in itself a notion of random effects from linear mixed models (LMMs) to model numerous phenomena, such as spatial data, time series or population stratification in genetics.

stat.AP