Marek Omelka

Nuclear mitochondrial DNA sequences (NUMTs) represent mitochondrial DNA fragments integrated into the nuclear genome with potential clinical significance particularly in the pathology of cancer which have be identified in recent whole-genome sequencing (WGS) studies. Combining NUMT in silico analysis on WGS from The Cancer Genome Atlas with further characterize with molecular-genomic experiments (PCR assay and sequencing) across lung adenocarcinoma (LUAD) patient cohort tumor samples and incorporating important clinical parameters. Our molecular analysis of 298 LUAD samples revealed a RSPO1 gene NUMT insertion in approximately 31% of cases (29% heterozygous, 2% homozygous). This RSPO1-NUMT insertion’s presence was observed across matched blood, healthy lung, and tumor samples confirming its germline origin. Notably, homozygous carriers exhibited significantly earlier disease onset (mean age: 54 vs. 63.3 years; P=0.04) and a trend toward advanced-stage disease at diagnosis compared to no NUMT-insertion or heterozygous individuals. We report a novel NUMT insertion of the RSPO1 gene, which is a key regulator in the oncogenic WNT signaling pathway. Our findings also highlight technical challenges in NUMT detection across genome builds and databases, with significant discrepancies observed between reference genomes and population frequency estimates. We propose that this homozygous RSPO1-NUMT insertion may represent a previously unrecognized predisposing factor for LUAD development and progression through modulation of RSPO1 expression and subsequent WNT pathway activation, potentially influencing tumor vascularization, drug response, and disease progression.

We consider the copula mapping, which maps a joint cumulative distribution function to the corresponding copula. Its Hadamard differentiability was shown in van der Vaart and Wellner (1996), Fermanian, Radulović and Wegkamp (2004) and (under less strict assumptions) in Bücher and Volgushev (2013). This differentiability result has proved to be a powerful tool to show the weak convergence of empirical copula processes in various settings using the functional delta method. We state a generalization of the Hadamard differentiability results and illustrate how it can be used for the derivations of asymptotic expansions and the weak convergence of empirical copula processes in the presence of covariates. The usefulness of this result is illustrated on several applications which include a multidimensional functional linear model, where the copula of the error vector describes the dependency between the components of the vector of observations, given the functional covariate.

Multivariate tail coefficients are an important tool when investigating dependencies between extreme events for different components of a random vector. Although bivariate tail coefficients are well-studied, this is, to a lesser extent, the case for multivariate tail coefficients. This paper contributes to this research area by (i) providing a thorough study of properties of existing multivariate tail coefficients in the light of a set of desirable properties; (ii) proposing some new multivariate tail measurements; (iii) dealing with estimation of the discussed coefficients and establishing asymptotic consistency; and, (iv) studying the behavior of tail measurements with increasing dimension of the random vector. A set of illustrative examples is given, and practical use of the tail measurements is demonstrated in a data analysis with a focus on dependencies between stocks that are part of the EURO STOXX 50 market index.

Anthropogenic disturbance may cause shifts in vegetation and alter the litter input. We studied the decomposition of different litter types under soil conditions of a nutrient-rich grassland and nutrient-poor forest to identify factors responsible for changes in the community structure and succession of microbial decomposers. This will help to predict the consequences of induced changes on the abundance and activity of microbial decomposers and recognize if the decomposition process and resulting quality and quantity of soil organic matter will be affected at various sites.