Discontinuous perturbations of nonhomogeneous strongly-singular Kirchhoff problems

In this paper, we are concerned with a Kirchhoff problem in the presence of a strongly-singular term perturbed by a discontinuous nonlinearity of the Heaviside type in the setting of Orlicz–Sobolev space. The presence of both strongly-singular and non-continuous terms brings up difficulties in associating a differentiable functional to the problem with finite energy in the whole space $$W_0^{1,\Phi }(\Omega )$$ W 0 1 , Φ ( Ω ) . To overcome this obstacle, we establish an optimal condition for the existence of $$W_0^{1,\Phi }(\Omega )$$ W 0 1 , Φ ( Ω ) -solutions to a strongly-singular problem, which allows us to constrain the energy functional to a subset of $$W_0^{1,\Phi }(\Omega )$$ W 0 1 , Φ ( Ω ) in order to apply techniques of convex analysis and generalized gradient in the sense of Clarke.

Comparative Assessment and Novel Strategy on Methods for Imputing Proteomics Data

Missing values are a major issue in quantitative proteomics analysis. While many methods have been developed for imputing missing values in high-throughput proteomics data, a comparative assessment of imputation accuracy remains inconclusive, mainly because mechanisms contributing to true missing values are complex and existing evaluation methodologies are imperfect. Moreover, few studies have provided an outlook of future methodological development. We first re-evaluate the performance of eight representative methods targeting three typical missing mechanisms. These methods are compared on both simulated and masked missing values embedded within real proteomics datasets, and performance is evaluated using three quantitative measures. We then introduce fused regularization matrix factorization, a low-rank global matrix factorization framework, capable of integrating local similarity derived from additional data types. We also explore a biologically-inspired latent variable modeling strategy - convex analysis of mixtures - for missing value imputation and present preliminary experimental results. While some winners emerged from our comparative assessment, the evaluation is intrinsically imperfect because performance is evaluated indirectly on artificial missing or masked values not authentic missing values. Nevertheless, we show that our fused regularization matrix factorization provides a novel incorporation of external and local information, and the exploratory implementation of convex analysis of mixtures presents a biologically plausible new approach.

Convergence Rates of First- and Higher-Order Dynamics for Solving Linear Ill-Posed Problems

Recently, there has been a great interest in analysing dynamical flows, where the stationary limit is the minimiser of a convex energy. Particular flows of great interest have been continuous limits of Nesterov’s algorithm and the fast iterative shrinkage-thresholding algorithm, respectively. In this paper, we approach the solutions of linear ill-posed problems by dynamical flows. Because the squared norm of the residual of a linear operator equation is a convex functional, the theoretical results from convex analysis for energy minimising flows are applicable. However, in the restricted situation of this paper they can often be significantly improved. Moreover, since we show that the proposed flows for minimising the norm of the residual of a linear operator equation are optimal regularisation methods and that they provide optimal convergence rates for the regularised solutions, the given rates can be considered the benchmarks for further studies in convex analysis.

Determining molecular archetype composition and expression from bulk tissues with unsupervised deconvolution

Complex tissues are composite ecological systems whose components interact with each other to create a unique physiological or pathophysiological state distinct from that found in other tissue microenvironments. To explore this ground yet dynamic state, molecular profiling of bulk tissues and mathematical deconvolution can be jointly used to characterize heterogeneity as an aggregate of molecularly distinct tissue or cell subtypes. We first introduce an efficient and fully unsupervised deconvolution method, namely the Convex Analysis of Mixtures - CAM3.0, that may aid biologists to confirm existing or generate novel scientific hypotheses about complex tissues in many biomedical contexts. We then evaluate the CAM3.0 functional pipelines using both simulations and benchmark data. We also report diverse case studies on bulk tissues with unknown number, proportion and expression patterns of the molecular archetypes. Importantly, these preliminary results support the concept that expression patterns of molecular archetypes often reflect the interactive not individual contributions of many known or novel cell types, and unsupervised deconvolution would be more powerful in uncovering novel multicellular or subcellular archetypes.

Comparative Assessment and Outlook on Methods for Imputing Proteomics Data

Background: Missing values are a major issue in quantitative proteomics data analysis. While many methods have been developed for imputing missing values in high-throughput proteomics data, comparative assessment on the accuracy of existing methods remains inconclusive, mainly because the true missing mechanisms are complex and the existing evaluation methodologies are imperfect. Moreover, few studies have provided an outlook of current and future development.Results: We first report an assessment of eight representative methods collectively targeting three typical missing mechanisms. The selected methods are compared on both realistic simulation and real proteomics datasets, and the performance is evaluated using three quantitative measures. We then discuss fused regularization matrix factorization, a popular low-rank matrix factorization framework with similarity and/or biological regularization, which is extendable to integrating multi-omics data such as gene expressions or clinical variables. We further explore the potential application of convex analysis of mixtures, a biologically-inspired latent variable modeling strategy, to missing value imputation. The preliminary results on proteomics data are provided together with an outlook into future development directions.Conclusion: While a few winners emerged from our comparative assessment, data-driven evaluation of imputation methods is imperfect because performance is evaluated indirectly on artificial missing or masked values not authentic missing values. Imputation accuracy may vary with signal intensity. Fused regularization matrix factorization provides a possibility of incorporating external information. Convex analysis of mixtures presents a biologically plausible new approach.