Biology subjects

Metzler, M.

Publications and source records attributed to Metzler, M..

4 recordsLinked to original sources

bioRxiv2026

T-Rex: Standardized Analysis of Germline Variants in Whole-Exome Sequencing Trios

Whole-exome sequencing (WES) enables the identification of rare germline variants contributing to pediatric diseases. Trio-based sequencing, comparing affected children with their parents, is particularly effective for rare disease genetics. However, WES data analysis requires bioinformatics expertise, varies across institutions, and is often incompatible with clinical workflows. We developed T-Rex (Trio Rare variant analysis of EXomes), a cross-platform desktop application that enables the standardized and local analysis of WES germline Trio data without the need for programming knowledge. T-Rex integrates state-of-the-art tools for alignment, dual-variant calling (GATK HaplotypeCaller + VarScan2), annotation (SNPEff/SNPSift), rare-variant filtering based on population frequencies (gnomAD), and family-based statistical testing, including the Transmission Disequilibrium Test with multiple-testing correction. Benchmarking of the dual-caller strategy on the Genome in a Bottle Ashkenazim Trio demonstrates high precision (99.2%) while maintaining robust sensitivity (91.1%). User testing (n=13) confirmed quick learning across clinicians and researchers. Application to a cohort of n=121 pediatric cancer Trio datasets, filtering for rare protein-coding variants (MAF[≤]0.1% in gnomAD v4.0), validated all assessable previously reported pathogenic variants. Overall, T-Rex enables clinicians to robustly analyze WES Trio data in compliance with data protection regulations without requiring additional software licenses. As one of the first platforms for comprehensive WES Trio analysis that requires no programming expertise while providing clinical-grade, end-to-end workflows, T-Rex facilitates collaborative research between clinics and reduces reliance on external providers. Implementation and AvailabilityThe source code is available on GitHub (https://github.com/SaraLuisaReh/trex). The fully precompiled app is available on Zenodo (https://zenodo.org/records/19135262).

bioinformatics↗

bioRxiv2025

Pupillary oscillations accompany hand movement planning in naturalistic scenes

Pupil diameter changes may be a useful signal source for noninvasive studies of motion planning. However, the pupil is also sensitive to luminance changes, making it difficult to study pupillary signals under natural conditions. Here we used pupillary hippus, a luminance-insensitive measure of high-frequency pupil dynamics while human participants planned naturalistic reaches in virtual reality. We found that hippus is significantly increased during planning compared to both rest and movement execution epoch. This finding shows pupillary dynamics change during motion planning reflecting preparatory processes. Most importantly, we demonstrate the potential of a new pupillometric method to study motion planning in natural conditions.

neuroscience↗

bioRxiv2023

Phantom touch illusion: Unexpected phenomenological effects of tactile gating in the absence of tactile stimulation

We report the presence of a tingling sensation perceived during self touch without physical stimulation. We used immersive virtual reality scenarios in which subjects touched their body using a virtual object. This touch resulted in a tingling sensation corresponding to the location touched on the virtual body. We called it "phantom touch illusion" (PTI). Interestingly the illusion was also present when subjects touched invisible (inferred) parts of their limb. We reason that this PTI results from tactile gating process during self-touch. The reported PTI when touching invisible body parts indicates that tactile gating is not exclusively based on vision, but rather on multi-sensory, top-down input involving body schema. This finding shows that representations of own body are defined top-down, beyond the available sensory information.

neuroscience↗

bioRxiv2018

Boundaries support specific long-distance interactions between enhancers and promoters in Drosophila Bithorax complex

Drosophila bithorax complex (BX-C) is one of the best model systems for studying the role of boundaries (insulators) in gene regulation. Expression of three homeotic genes, Ubx, abd-A, and Abd-B, is orchestrated by nine parasegment-specific regulatory domains. These domains are flanked by boundary elements, which function to block crosstalk between adjacent domains, ensuring that they can act autonomously. Paradoxically, seven of the BX-C regulatory domains are separated from their gene target by at least one boundary, and must \"jump over\" the intervening boundaries. To understand the jumping mechanism, the Mcp boundary was replaced with Fab-7 and Fab-8. Mcp is located between the iab-4 and iab-5 domains, and defines the border between the set of regulatory domains controlling abd-A and Abd-B. When Mcp is replaced by Fab-7 or Fab-8, they direct the iab-4 domain (which regulates abd-A) to inappropriately activate Abd-B in abdominal segment A4. For the Fab-8 replacement, ectopic induction was only observed when it was inserted in the same orientation as the endogenous Fab-8 boundary. A similar orientation dependence for bypass activity was observed when Fab-7 was replaced by Fab-8. Thus, boundaries perform two opposite functions in the context of BX-C - they block crosstalk between neighboring regulatory domains, but at the same time actively facilitate long distance communication between the regulatory domains and their respective target genes.\n\nAuthor SummaryDrosophila bithorax complex (BX-C) is one of a few examples demonstrating in vivo role of boundary/insulator elements in organization of independent chromatin domains. BX-C contains three HOX genes, whose parasegment-specific pattern is controlled by cis-regulatory domains flanked by boundary/insulator elements. Since the boundaries ensure autonomy of adjacent domains, the presence of these elements poses a paradox: how do the domains bypass the intervening boundaries and contact their proper regulatory targets? According to the textbook model, BX-C regulatory domains are able to bypass boundaries because they harbor special promoter targeting sequences. However, contrary to this model, we show here that the boundaries themselves play an active role in directing regulatory domains to their appropriate HOX gene promoter.

genetics↗