Biology subjects

Sauer, M.

Publications and source records attributed to Sauer, M..

At least 19 recordsLinked to original sources

bioRxiv2026

A Normative Model Reveals Functional Optimization of Synaptic Nano-Architecture

Super-resolution microscopy approaches have revealed that synaptic proteins are not randomly distributed within individual synapses. Rather, they form sub-synaptic clusters that may be coordinated between the synaptic compartments, thereby forming transsynaptic nanocolumns. However, the functional significance of this nano-architecture remains under debate. In particular, it is unclear whether the positions of synaptic proteins optimize a specific cost function. Here, we present a normative modeling framework that integrates synaptic nano-architecture imaged with STED and dSTORM microscopy with synaptic transmission recorded with electrophysiology at the Drosophila neuromuscular junction (NMJ). Model-based quantification showed that clusters of Unc13A, which likely demark presynaptic release sites, and postsynaptic glutamate receptors (GluRs) adopt aligned ring-like arrangements in individual synapses. We developed an analytical description of GluR activation relative to presynaptic release position, enabling to link super-resolution imaging data with recorded postsynaptic current amplitudes without relying on costly Markov chain Monte Carlo (MCMC) simulations. Our model predicts that glutamate released from a single vesicle spreads across the entire receptor population. Given this spread, the postsynaptic current amplitude is maximized when glutamate is released close to the active zone (AZ) center, in contradiction to the observed offset of Unc13A clusters. However, the observed relative positions of Unc13A and GluR clusters maximize the postsynaptic current amplitude and minimize the delay between vesicle release and receptor activation during multivesicular release. Hence, transsynaptically-aligned Unc13A-GluR rings optimize for multivesicular but not univesicular release. Given that multivesicular release is mainly observed during enhanced presynaptic release at the Drosophila NMJ, transsynaptic nano-architecture may be adapted to elevated presynaptic release states.

neuroscience↗

bioRxiv2026

Structural cell biology by mega-expansion microscopy

Structural characterization of macromolecular assemblies within intact cells remains one of the central challenges in cell biology. While cryo-electron tomography provides unparalleled structural information, its applicability is limited by sample thickness, imaging throughput, and accessibility. Fluorescence microscopy offers molecular specificity and compatibility with intact biological specimens but has so far lacked the spatial resolution required to visualize cellular ultrastructure. Here we introduce Mega-expansion microscopy (Mega-ExM), a fluorescence imaging approach that enables structural visualization of whole cells using conventional confocal microscopes. Mega-ExM combines iterative hydrogel expansion with whole-proteome NHS-dye labeling and post-expansion immunostaining to achieve tunable expansion factors of up to [~]1,500-fold while preserving ultrastructure. At expansion factors of 40-260x, Mega-ExM resolves centrioles, mitochondrial cristae, protein-dense domains within mitochondrial cristae consistent with respiratory-chain supercomplexes, the synaptonemal complex, and nuclear pore complexes (NPCs) with high fidelity. Particle averaging of [~]200x expanded NPCs yields reconstructions with a structural resolution of [~]35 [A], approaching what cryo-electron tomography has achieved for selected protein assemblies. By combining molecular specificity, large imaging volumes, and nanoscale structural resolution on conventional fluorescence microscopes, Mega-ExM establishes a broadly accessible platform for in situ structural biology.

biophysics↗

bioRxiv2026

Programmable protein reference standards for benchmarking sub-10-nm fluorescence microscopy

Fluorescence microscopy is increasingly used to measure molecular organization at length scales where labeling, photophysics and sample preparation can dominate quantitative accuracy. Reference standards are therefore needed that combine defined nanoscale geometry with a protein-like environment and compatibility with biological imaging. Here we introduce circular tandem repeat protein as programmable protein standards for benchmarking sub-10-nm fluorescence microscopy. Using genetic code expansion and bioorthogonal labeling, we generated compact protein rings carrying up to six labeling sites. Photoswitching fingerprint analysis revealed geometry-dependent localization accumulation and blinking kinetics, demonstrating that short-range fluorophore interactions can be assessed as measurable benchmark parameters. DNA-PAINT confirmed accessible docking sites and programmed valency at the single-particle level. We further established recombinant tethering and genetically encoded membrane display, extending the standards to cellular environments. cTRP PicoRulers were also compatible with expansion microscopy. Together, cTRPs provide a modular protein-based platform for evaluating molecular-scale imaging performance in purified and cellular environments.

biophysics↗

bioRxiv2026

M-CSF stimulated alveolar macrophages safeguard from invasive aspergillosis

Invasive pulmonary aspergillosis (IPA) is a life-threatening complication in immunocompromised individuals, including recipients of allogeneic hematopoietic cell transplantation (allo-HCT). While systemic neutropenia is traditionally considered the primary risk factor for IPA, we demonstrate that tissue-resident alveolar macrophages (AMs), rather than recruited neutrophils, dictate survival during the critical early window after transplantation. Utilizing an ultra-low dose Aspergillus fumigatus infection model that mimics physiological exposure, we identify alveolar macrophages (AMs) as key players in pulmonary antifungal defense. In immunocompromised mice, AMs conferred protection against lethal invasive aspergillosis by day 6, but not day 4 post-allo-HCT. To enhance AM function at the earlier time point, we tested cytokine-based interventions and show that M-CSF, but not IL-34, which both bind to the CSF-1 receptor, promotes migratory activity, phagolysosomal function and fungal killing in both mouse and human primary tissue-resident AMs. In allo-HCT recipient mice, M-CSF treatment preserved lung tissue integrity, suppressed pro-inflammatory cytokines, and protected mice from lethal invasive aspergillosis. The M-CSF-driven protective effect was abrogated upon AM depletion. Our findings demonstrate a critical role of tissue-resident AMs in pulmonary antifungal immunity and suggest that therapeutic modulation of AM activity via M-CSF may offer a promising strategy to combat severe fungal infections in immunocompromised patients. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=107 SRC="FIGDIR/small/736478v1_ufig1.gif" ALT="Figure 1"> View larger version (51K): org.highwire.dtl.DTLVardef@49ba37org.highwire.dtl.DTLVardef@607c4forg.highwire.dtl.DTLVardef@814894org.highwire.dtl.DTLVardef@1c413c9_HPS_FORMAT_FIGEXP M_FIG C_FIG

immunology↗

bioRxiv2026

Two-dye-imager DNA-PAINT enables volumetric nanoscopy of expanded cells

Refined single-molecule localization microscopy methods demonstrated superior localization precisions on isolated sample but remain limited by labeling density and imaging speed in cells. Here we combine expansion microscopy (ExM) with two-dye-imager (TDI)-DNA-PAINT to resolve fine molecular details of protein assemblies in [~]8-fold expanded cells with nanometer resolution. Using lattice light-sheet (LLS) microscopy, Ex-TDI-DNA-PAINT provides a robust platform for three-dimensional (3D) volumetric nanoscopy of the molecular organization of cells.

biophysics↗

bioRxiv2026

Chlamydia trachomatis deploys sphingolipids for genome organisation

Chlamydia trachomatis is an obligate intracellular bacterial pathogen and a leading cause of sexually transmitted infections worldwide. During its biphasic developmental cycle, infectious, non-replicative elementary bodies alternate with replicative reticulate bodies within a membrane-bound intracellular niche known as the inclusion. C. trachomatis relies heavily on host-derived metabolites, including sphingolipids, which are essential for inclusion integrity, bacterial growth and production of infectious progeny. Here, using expansion microscopy, we uncover an unexpected localization of sphingolipid derivatives within the highly condensed DNA nucleoids of elementary bodies. These sphingolipids are released from nucleoids prior to DNA decondensation during the elementary-to-reticulate body transition, the earliest phenotypic event in the complex developmental cycle of these bacteria. Thereafter, nucleoids undergo a characteristic DNA decondensation process that we visualized by expansion microscopy. By combining super-resolution imaging with a FRET-based metabolic tracking approach and lipidomics, we identified sphingomyelin derived from the sphingolipid analogues as the sphingolipid species predominantly associated with the condensing nucleoids of elementary bodies. Notably, reticulate bodies arrested in their developmental stage fail to accumulate sphingomyelin, suggesting a role for this lipid in stage-specific DNA condensation. Together, our findings suggest an unanticipated role for sphingolipids in bacterial DNA organization and developmental regulation in C. trachomatis.

microbiology↗

bioRxiv2026

Nanoscale imaging of expanded cells and proteins with spontaneously blinking dyes

Expansion microscopy (ExM) enables nanoscale imaging on standard microscopes, but combining ExM with single-molecule localization microscopy (SMLM) remains difficult, owing to the incompatibility of expanded hydrogels with photoswitching buffers. Here, we introduce a single-step expansion microscopy method that allows SMLM with spontaneously blinking dyes in 6-14x expanded samples, without re-embedding. We demonstrate nanometer-resolution imaging by resolving the organization of the nuclear pore complex (NPC) and the molecular structure of recombinant homotrimeric proliferating cell nuclear antigen (PCNA).

biophysics↗

bioRxiv2025

Towards improved particle averaging for single-molecule localization microscopy using geometric deep learning

Single-molecule localization microscopy (SMLM) can resolve intracellular structures down to the nanoscale, but often produces sparse and incomplete data. Particle averaging (PA) can aid with the reconstruction of complete structures, but traditional PA methods can suffer from template bias or the high computational costs of geometric alignment. To address these limitations, we developed a geometric deep learning (GDL) framework for enhanced, template-free 3D particle averaging. Our pipeline uses a GDL autoencoder, trained on realistic simulated data, to map incomplete point clouds into a robust latent space. By averaging feature vectors directly within this space, our method bypasses the need for explicit 3D alignment. We validated our approach on simulated DNA origami and experimental nuclear pore complex (NPC) data. The latent space averaging successfully reconstructed NPC structures with key metrics (ring radius {approx} 46 nm, ring distance {approx} 52 nm) that are comparable to state-of-the-art methods. This work establishes a viable GDL pipeline for SMLM analysis, offering an efficient alternative to traditional PA. While the current model requires structure-specific training, our results highlight the significant potential of GDL for quantitative structural biology.

bioinformatics↗

bioRxiv2025

NanTex enables computational multiplexing and phenotyping of organelles across super-resolution modalities

Super-resolution microscopy (SRM) enables nanoscale visualization of cellular organelles but remains constrained by spectral overlap, labeling requirements, and temporal offsets in multicolor imaging. We present NanTex, a deep learning framework that introduces nanotexture as a universal descriptor of subcellular organization and achieves probabilistic demixing of multiple organelles from single-channel SRM images. Unlike segmentation methods that enforce exclusivity, NanTex preserves overlapping morphologies, enabling faithful reconstruction even in crowded regions. Trained on small curated datasets with augmentation, NanTex generalized across SMLM, MINFLUX, STED, SIM, and live-cell Airyscan, with modality-specific retraining where necessary. Demonstrated on cytoskeletal, endomembrane, and metabolic organelles, NanTex achieved high-fidelity reconstructions and extended uniquely to live-cell imaging, where it eliminated temporal misalignment and enabled quantitative tracking of vesicle-like ER subdomains. Notably, NanTex enables quantitative dynamic readouts directly from single-channel live-cell data, revealing and tracking hidden subdomains in real time without the need for additional labels. Beyond multiplexing, NanTex supported computational phenotyping by distinguishing structurally distinct yet molecularly identical populations, exemplified by nocodazole-induced microtubule depolymerization and its glyoxal-mediated modulation. Together, these results establish nanotexture as a paradigm-shifting descriptor for organelle identity and position NanTex as a modality-agnostic, label-efficient, and live-cell-ready strategy for quantitative nanoscale biology. Significance StatementNanTex reframes multiplexing as texture-based demixing, introducing nanotexture as a universal fingerprint of organelle identity. By enabling quantitative, label-efficient reconstructions across SRM modalities and live-cell phenotyping, including vesicle tracking from single-channel data, NanTex opens a path to studying organelle remodeling and disease progression with unprecedented fidelity across SRM modalities.

biophysics↗

bioRxiv2025

Comparative gene regulatory network mapping of Brassicaceae members with differential drought tolerance

Climate change is projected to intensify weather extremes like droughts that threaten global crop yields. While many crops are sensitive to water deprivation, they have drought-tolerant wild relatives; however, the molecular basis for this differential tolerance among closely related species remains unclear. We previously investigated this using transcriptomics in the Brassicaceae family, comparing the drought-sensitive reference plant Arabidopsis thaliana (Ath) with its drought-tolerant relatives Arabidopsis lyrata (Aly) and Eutrema salsugineum (Esa), uncovering key differences that may underlie their respective phenotypes. Here, to elucidate the regulatory architecture driving these differences, we mapped drought-responsive gene regulatory networks (GRNs) for all three species using the yeast one-hybrid (Y1H) approach. We cloned promoters of orthologs with divergent drought-induced expression patterns and screened them against the Ath transcription factor (TF) collection, generating a quality-controlled cross-species drought-responsive GRN map encompassing 1,137 high-confidence TF-promoter interactions. Comparative analysis revealed that the tolerant species share greater regulatory similarity and exhibit higher network connectivity than Ath. An Esa-specific expansion of bZIP TF interactions was observed, consistent with an enrichment of G-box motifs in its genome and in drought-upregulated genes. Several observed changes affect the ABA signalling pathway: Ath gained a susceptibility linked GBF3-CYP707A1 edge, whereas Esa acquired tolerance associated ABF-mTERF10 interactions. Furthermore, network-rewiring analysis uncovered a novel role for ASIL2 in stress response. Finally, our network highlights TFs (CSDP1, ERF4, HB6, and MYB73) that likely contribute to the "stress-primed" state of Aly and Esa. Our work provides a broadly applicable framework for comparative GRN mapping and a valuable resource for improving drought tolerance in crops.

plant biology↗

bioRxiv2025

Single-molecule localization microscopy reveals the molecular organization of endogenous membrane receptors

Super-resolution microscopy in combination with genetic labeling methods allows imaging of single proteins in cells. However, visualizing endogenous proteins on primary cells remains challenging due to the use of sterically demanding antibodies for labeling. Here, we demonstrate how immunolabeling conditions and antibody crosslinking influence the quantification and identification of membrane receptor stoichiometry on cells using single-molecule localization microscopy. We developed an optimized immunolabeling and analysis protocol and demonstrate the performance of the approach by resolving the molecular organization of endogenous CD45, CD69, and CD38 on Jurkat T cells. To demonstrate the usefulness of the method for immunotherapy applications we investigated the interaction of primary multiple myeloma cells with the therapeutic monoclonal antibodies (mAbs) daratumumab and isatuximab, and a polyclonal anti-CD38 antibody. Our approach might lay the foundation for improved personalized diagnostics and treatment with therapeutic antibodies. One-Sentence SummarySingle-molecule localization microcopy quantifies the expression and resolves the stoichiometry of endogenous membrane receptors

biophysics↗

bioRxiv2025

Resolving protein organization in cells with nanometer resolution

Advances in super-resolution microscopy have outpaced molecular labeling methods, impeding nanometer-scale imaging of endogenous multiprotein complexes in cells. To overcome these limitations, we developed an expansion microscopy (ExM) approach based on double-homogenized hydrogels that enables direct stochastic optical reconstruction microscopy (dSTORM) of 7-8-fold expanded immunolabeled samples. The resulting [~]4-fold increase in effective immunolabeling density resolved the 8 nm distance between neighboring -tubulin molecules in microtubules and the polyhedral lattice in clathrin-coated pits with nanometer precision in cells. Two-color Ex-dSTORM further revealed the molecular organization of RIM scaffolding protein and Munc13-1, an essential synaptic vesicle priming protein, in ring-like structures with diameters of 40-45 nm at the presynapse in hippocampal neurons. Our results demonstrate that Ex-dSTORM resolves the molecular organization of endogenous multiprotein complexes with nanometer spatial resolution in genetically unmodified cells. Thus, it provides a versatile method for the investigation of molecular protein distributions in their physiologically relevant context. One-Sentence SummaryThe optimized combination of dSTORM and double TREx ExM resolves previously unresolvable protein assemblies in cells

biophysics↗

bioRxiv2025

Cryopreservation of siRNA-treated cells is feasible

Cryopreservation is a routine step in the manufacturing process of adoptive cell therapies, providing critical logistic flexibility. RNAi-based therapies are increasingly being explored as enhancers or modulators of adoptive cell therapies. However, the impact of cryopreservation on cells treated with RNAi-based therapies has not been investigated before. In this study, we addressed this knowledge gap by examining silencing efficacy in siRNA-treated cells that undergo cryopreservation. Our findings demonstrate that silencing in cryopreserved cells is comparable to that in cells maintained continuously in culture. Moreover, we found that the duration of siRNA exposure plays a significant role in cells that later undergo cryopreservation, with extended exposure improving silencing efficiency. However, this effect diminishes at higher siRNA concentrations. Additionally, we showed that siRNA treatment is feasible at low temperatures (2-8{degrees}C), and siRNA-treated cells can be cryopreserved for extended periods (at least one month) without loss of efficacy. Furthermore, we demonstrated the feasibility of cryopreserving siRNA-treated primary cells, including those resembling leukapheresis material. Our work establishes the feasibility of integrating siRNA treatments into current manufacturing processes for adoptive cell therapies.

bioengineering↗

bioRxiv2025

miRNA Mimic Optimization: Chemical Structure - Activity - Targetome Relationship to Engineer Selective Anti-Tumor Immunity in T cells

MicroRNA (miRNA) mimic therapies act through a broad and complex targetome in disease contexts. However, both the composition of these targetomes and the impact of chemical modifications on them remain poorly understood. In this study, we investigate eight fully chemically modified miRNA scaffolds across three miRNA sequences in a model immune disorder, graft-versus-host-disease (GvHD), which is an off-tumor effect of allogeneic T cell therapy. We demonstrate that conventional silencing assays fail to predict the functional performance of miRNA mimics in GVHD and graft-versus-leukemia (GvL), the on-tumor effect of allogeneic T cells. Moreover, we find that chemical scaffolds influence the duration of silencing mediated by miRNA mimics. We identify a miR-374b version as a lead miRNA candidate that not only inhibits GVHD but also enhances GVL--an unprecedented and desired improvement in on-versus-off-tumor selectivity of clinical relevance. Further analysis reveals distinct responder and non-responder groups to miR-374b therapy. While responders exhibit significant transcriptomic shifts, non-responders show virtually no changes, despite intact miRNA pathway function, underscoring a strong correlation between transcriptome reprogramming and therapeutic efficacy. RNA sequencing reveals that miR-374b acts via metabolic reprogramming of T cells and induces partially distinct transcriptional programs in GVHD and GVL. Collectively, our findings demonstrate that fully chemically modified miRNA mimic therapies are feasible to rewrite the T-cell transcriptome, profoundly improving on-versus-off-tumor specificity in T-cell-mediated cancer therapies.

bioengineering↗

bioRxiv2025

Improving single molecule localisation microscopy reconstruction by extending the temporal context

Single-molecule localization microscopy methods such as dSTORM require specific buffer conditions to enable blinking and detection of individual emitters, making them incompatible with live cell imaging and expansion microscopy. An alternative approach to achieve super-resolution without blinking is to observe the fluctuations of the emitter intensity over time. Existing localization algorithms for high-emitter density make use of radial symmetry or use artificial neural networks trained on single high-density frames to predict emitter positions. Here, we aim to improve the resolution by using a larger temporal context. We combine the U-Net architecture used previously for image reconstruction with multi-head attention used in the Transformer architecture. We compare the results to DECODE and eSRRF as well as to traditional fitting algorithms on public benchmark data. A generic pre-trained model is provided together with a fast and robust simulator for training data and all scripts needed to train custom networks.

biophysics↗

bioRxiv2025

RBM20-variants induce distinct calcium handling and metabolic phenotypes in patient-specific stem cell models of dilated and non-compaction cardiomyopathy

Background and aimMutations in the splice regulator RBM20 account for [~]3 % of genetic cardiomyopathies. In particular, the highly conserved RS domain is a hotspot for disease-associated mutations. Previously, mutations at same amino acid position 634 in the hotspot RS-domain were found to cause dilated cardiomyopathy (DCM) with left ventricular non-compaction (R634L) or without (R634W), but the pathophysiological mechanisms that govern the heterogeneity in phenotype presentation remained unknown. Here, we identify the molecular events caused by the distinct RBM20 mutations from DCM and left-ventricular non-compaction (LVNC) using patient-specific stem cell models. MethodsWe generated induced pluripotent stem cell-derived cardiomyocytes (iPSC-CM) of one LVNC- and two DCM-patients harboring the RBM20-mutations R634L (LVNC) or R634W (DCM). We investigated alternative splicing activity, RBM20 localization, sarcomeric regularity, cAMP level, kinase-specific phosphorylation of key Ca2+ handling enzymes, physiological cardiac functions as Ca2+ homeostasis, and metabolic activity on a patient-specific cardiomyocyte level. Force generation was analyzed in patient-specific engineered myocardial tissues. Isogenic rescue and mutation insertion lines were generated by CRISPR/Cas9 technology to analyze the direct impact of the RBM20 mutations on the cardiac phenotype. ResultsWe observed common splicing aberrations for LVNC- and DCM-CM in TTN and RYR2, RBM20 cytoplasmatic accumulation and irregular sarcomeric structure. LVNC-CM harboring the RBM20-p.R634L variant show distinct molecular, cellular and functional impairments that manifest in CAMK2D, TRDN and IMMT mis-splicing. Splicing defects in LVNC-CM correlate with elevated systolic Ca2+ and faster Ca2+ kinetics with elevated cAMP levels and PLN-hyperphosphorylation. An increased metabolic activity and mitochondrial membrane potential support the hyperactive LVNC-CM. By contrast, DCM-CM (RBM20-p.R634W) distinctly present with decreased systolic Ca2+ and increased SR Ca2+leak but unchanged Ca2+ kinetics and metabolic activity. Both mutations lead to severely reduced force of contraction in engineered myocardium. CRISPR/Cas9 gene-edited isogenic control lines of both described RBM20 mutations in LVNC and DCM demonstrated the causative nature of the two mutations and their diverging effects. Further, L-type Ca2+ channel blockade by verapamil ameliorates the Ca2+ cycling and leakage phenotypes in LVNC- and DCM-CM. ConclusionWe show the first comparative iPSC-model of splice-defect-associated RBM20-dependent LVNC-p.R634L and DCM-p.R634W. We found shared and variant-specific phenotypes on a patient-specific level. Our data demonstrate that the different RBM20 mutations manifest in distinct molecular aberrations in alternative splicing and RBM20 cytoplasmic accumulation that convey various physiological impairments in structure, Ca2+ handling, metabolism and contractile force.

molecular biology↗

bioRxiv2024

Base edited "universal" donor CAR T cell strategies for acute myeloid leukaemia

Acute myeloid leukaemia (AML) is often aggressive and life-threatening with limited curative options. Immunotherapies including chimeric antigen receptor (CAR) T cell approaches are under investigation, but high levels of disease heterogeneity remain a major hurdle to achieving durable responses. Targeting of multiple surface antigens may ensure complete immunological coverage of leukemic blast populations, but such antigens are often also present on healthy haematopoietic populations. To address likely aplasia, strategies can be designed to bridge CAR T cell therapies to allogeneic stem cell transplantation (allo-SCT), as demonstrated in recent anti-CD7 CAR T cell studies. Here we report that monotherapy using base edited (BE) universal donor CAR T cells against CD33, CLL-1, or CD7 delivered inhibition of AML in immunodeficient mice when antigen expression was homogenous, but combined use of BE-CAR33 and BE-CARCLL-1 T cells was required to address heterogenous CLL-1-/+CD33-/+ disease. We also demonstrate that removal of shared CD7 antigens enabled compatibility of BE-CAR33 with BE-CAR7 T cells, including in a patient-derived xenograft (PDX) model of AML. Therapeutic strategies envisage pick and mix applications of base edited universal CAR T cells in combinations determined by patient-specific antigen profiles. Such approaches also offer the possibility of deep, cell-based, de-bulking and preparative conditioning ahead of allo-SCT followed by donor-derived reconstitution.

immunology↗

bioRxiv2024

Parallel in-depth analysis of repeat expansions: an updated Clin-CATS workflow for nanopore R10 flow cells

Hereditary ataxias, caused by expansions of short tandem repeats, are difficult to diagnose using traditional PCR and Southern blot methods, which struggle to detect complex repeat expansions and cannot assess repeat interruptions or methylation. We present an updated Clinical Nanopore Cas9-Targeted Sequencing (Clin-CATS) workflow for analyzing repeat expansions, now compatible with the Oxford Nanopore Technologies R10 flow cell. The workflow incorporates the ONT wf-human-variation Epi2Me workflow, including the Straglr tool to analyze basecalled reads, ensuring compatibility with past, current, and future sequencing chemistries. It expands the number of genes analyzed from 10 to 27 within the ataxia panel and introduces new gene panels for myopathy, neurodegeneration, and ALS/motor neuron disease. Validated with Coriell reference and clinical samples, this method improves the analysis of pathogenic repeat expansions, providing deeper insights into repeat structures while addressing the limitations of traditional approaches.

genetics↗