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Motivation DNA CpG methylation (CpGm) has proven to be a crucial epigenetic factor in the gene regulatory system. Assessment of DNA CpG methylation values via whole-genome bisulfite sequencing (WGBS) is, however, computationally extremely demanding.
Results We present FAst MEthylation calling (FAME), the first approach to quantify CpGm values directly from bulk or single-cell WGBS reads without intermediate output files. FAME is very fast but as accurate as standard methods, which first produce BS alignment files before computing CpGm values. We present experiments on bulk and single-cell bisulfite datasets in which we show that data analysis can be significantly sped-up and help addressing the current WGBS analysis bottleneck for large-scale datasets without compromising accuracy.
Availability An implementation of FAME is open source and licensed under GPL-3.0 at https://github.com/FischerJo/FAME.
Investigators in the cognitive neurosciences have turned to Big Data to address persistent replication and reliability issues by increasing sample sizes, statistical power, and representativeness of data. While there is tremendous potential to advance science through open data sharing, these efforts unveil a host of new questions about how to integrate data arising from distinct sources and instruments. We focus on the most frequently assessed area of cognition - memory testing - and demonstrate a process for reliable data harmonization across three common measures. We aggregated raw data from 53 studies from around the world which measured at least one of three distinct verbal learning tasks, totaling N = 10,505 healthy and brain-injured individuals. A mega analysis was conducted using empirical bayes harmonization to isolate and remove site effects, followed by linear models which adjusted for common covariates. After corrections, a continuous item response theory (IRT) model estimated each individual subject’s latent verbal learning ability while accounting for item difficulties. Harmonization significantly reduced inter-site variance by 37% while preserving covariate effects. The effects of age, sex, and education on scores were found to be highly consistent across memory tests. IRT methods for equating scores across AVLTs agreed with held-out data of dually-administered tests, and these tools are made available for free online. This work demonstrates that large-scale data sharing and harmonization initiatives can offer opportunities to address reproducibility and integration challenges across the behavioral sciences.
The Calderón problem with finitely many unknowns is equivalent to convex semidefinite optimization
(2023)
We consider the inverse boundary value problem of determining a coefficient function in an elliptic partial differential equation from knowledge of the associated Neumann-Dirichlet-operator. The unknown coefficient function is assumed to be piecewise constant with respect to a given pixel partition, and upper and lower bounds are assumed to be known a-priori.
We will show that this Calderón problem with finitely many unknowns can be equivalently formulated as a minimization problem for a linear cost functional with a convex non-linear semidefinite constraint. We also prove error estimates for noisy data, and extend the result to the practically relevant case of finitely many measurements, where the coefficient is to be reconstructed from a finite-dimensional Galerkin projection of the Neumann-Dirichlet-operator.
Our result is based on previous works on Loewner monotonicity and convexity of the Neumann-Dirichlet-operator, and the technique of localized potentials. It connects the emerging fields of inverse coefficient problems and semidefinite optimization.