Malte Spielmann

Sphingolipid-Driven Lipotoxicity Promotes Calcific Aortic Valve Disease Through ER-Stress-NF-κB-EndMT Signaling and Is Therapeutically Targetable Through Serine Palmitoyltransferase Inhibition

This study identifies ceramide-driven lipotoxicity as a driver of calcific aortic valve disease and shows that SPT inhibition can reverse disease progression in vivo.

AUTOMATED VERSUS MANUAL REANALYSIS IN RARE DISEASE GENOMICS

The paper compares automated and manual reanalysis of rare disease genome sequencing data, finding automated methods achieve similar results with less effort.

Single-cell resolution uncovers cell type-specific dysregulation in Parkin-deficient neuron-microglia co-cultures

The paper uses single-nucleus RNA sequencing to identify cell type-specific dysregulation in Parkin-deficient neuron-microglia co-cultures, revealing distinct pathway disturbances in dopaminergic neurons and microglia.

Evaluating Genome Sequencing Strategies: Trio, Singleton, and Standard Testing in Rare Disease Diagnosis

This study compares trio, singleton, and standard genome sequencing in rare disease diagnosis, finding trio sequencing has the highest diagnostic yield.

Vascularized midbrain assembloids show neuroinflammation and dopaminergic neuron vulnerability in Parkinsons Disease

This study creates vascularized midbrain organoids to model Parkinson's disease, showing increased neuroinflammation and dopaminergic neuron vulnerability in patient-derived assembloids.

Astrocytes in the mouse suprachiasmatic nuclei respond directly to glucocorticoids feedback

The paper shows adult mouse SCN astrocytes respond to glucocorticoids through GR activation, influencing circadian rhythms and highlighting astrocytic roles in time-keeping.

A single-cell transcriptional timelapse of mouse embryonic development, from gastrula to pup

12.4 million single-nucleus transcriptomes from 83 staged mouse embryos (E8 to P0) yield 190 cell types, a zygote-to-pup cell-type tree, and rapid postnatal transcriptional shifts.

Interaction of mitochondrial polygenic score and environmental factors in LRRK2 p.Gly2019Ser parkinsonism

This study examines how a mitochondrial polygenic score interacts with environmental factors to influence age at onset in LRRK2-PD and iPD, finding ethnic-specific effects and gene-environment interactions.

Single cell, whole embryo phenotyping of pleiotropic disorders of mammalian development

The paper uses single-cell RNA sequencing to systematically phenotype mouse genetic models, identifying molecular and cellular changes across multiple mutants and wildtypes.

GestaltMatcher: Overcoming the limits of rare disease matching using facial phenotypic descriptors

GestaltMatcher improves diagnosis of ultra-rare genetic disorders by matching facial phenotypes to molecular diagnoses using a deep learning model trained on a large dataset of patient photographs.

Combinatorial effects on gene expression at the Lbx1/Fgf8 locus resolve Split-Hand/Foot Malformation type 3

The paper investigates how genomic rearrangements at the Lbx1/Fgf8 locus cause SHFM3 by altering chromatin structure and gene expression in mice.

Systematic reconstruction of the cellular trajectories of mammalian embryogenesis

This paper reconstructs cellular trajectories of mammalian embryogenesis using scRNA-seq data and identifies key transcription factors at branch points.

VarFish - Collaborative and Comprehensive Variant Analysis for Diagnosis and Research

VarFish is a web application for variant analysis in rare disease genetics, offering quality control, filtering, annotation, and collaboration tools for diagnostic and research use.

PEDIA: Prioritization of Exome Data by Image Analysis

The paper introduces an AI-driven method that uses facial images to prioritize exome data, achieving 99% top-10 accuracy in identifying disease-causing genes.