Biology subjects

Ruehle, M.

Publications and source records attributed to Ruehle, M..

3 recordsLinked to original sources

bioRxiv2024

Comprehensive and accurate genome analysis at scale using DRAGEN accelerated algorithms

Research and medical genomics require comprehensive and scalable solutions to drive the discovery of novel disease targets, evolutionary drivers, and genetic markers with clinical significance. This necessitates a framework to identify all types of variants independent of their size (e.g., SNV/SV) or location (e.g., repeats). Here we present DRAGEN that utilizes novel methods based on multigenomes, hardware acceleration, and machine learning based variant detection to provide novel insights into individual genomes with [~]30min computation time (from raw reads to variant detection). DRAGEN outperforms all other state-of-the-art methods in speed and accuracy across all variant types (SNV, indel, STR, SV, CNV) and further incorporates specialized methods to obtain key insights in medically relevant genes (e.g., HLA, SMN, GBA). We showcase DRAGEN across 3,202 genomes and demonstrate its scalability, accuracy, and innovations to further advance the integration of comprehensive genomics for research and medical applications.

genomics↗

bioRxiv2023

Neural adaptation at stimulus onset and speed of neural processing as critical contributors to speech comprehension independent of hearing threshold or age

Loss of afferent auditory fiber function (cochlear synaptopathy) has been suggested to occur before a clinically measurable deterioration of subjective hearing threshold. This so-called "hidden" hearing loss is characterized by speech comprehension difficulties. We examined young, middle-aged, and older individuals with and without hearing loss using pure-tone (PT) audiometry, short-pulsed distortion-product otoacoustic emissions (DPOAE), auditory brainstem responses (ABR), auditory steady state responses (ASSR), speech comprehension (OLSA), and syllable discrimination in quiet and noise. After normalizing OLSA thresholds for PT thresholds ("PNOT"), differences in speech comprehension still remained and showed no significant dependence on age, allowing us to categorize participants into groups with good, standard, and poor speech comprehension. Listeners with poor speech comprehension in quiet exhibited smaller firing rate adaptions at stimulus onset (as measured by the difference between DPOAE threshold and pure-tone threshold) and delayed supra-threshold ABR waves I-V, suggesting high spontaneous rate low threshold fiber cochlear synaptopathy. In contrast, when speech comprehension was tested in noise, listeners with poor speech comprehension had larger DPOAEs acceptance rate, putatively resulting from altered basilar membrane compression (recruitment). This was linked with higher uncomfortable loudness levels and larger ASSR amplitudes. Moreover, performance in phoneme discrimination was significantly different below (/o/-/u/) and above the phase-locking limit (/i/-/y/), depending on whether vowels were presented in quiet or ipsilateral noise. This suggests that neural firing rate adaptation at stimulus onset is critical for speech comprehension, independent of hearing threshold and age, whereas the recruitment phenomenon counterbalances the loss in speech-in-noise discrimination due to impaired threshold. Significance StatementAge-related hearing loss is the third largest modifiable risk factor for cognitive decline. It has been suggested that the link between hearing loss and cognitive decline is not fully explained by hearing threshold loss. We here suggest that language comprehension deficits may be used as an early indication of future hearing loss and therefore cognitive decline. We found that, independent of age and pure-tone thresholds, speech comprehension in quiet and ipsilateral noise depend on different onset firing-rate adaptations of inner hair cells (measured by DPOAE threshold), along with cochlear synaptopathy of high spontaneous rate auditory nerve fibers and neural spiking synchronicity. These measures may be used as possible future indicators of risk for cognitive decline.

neuroscience↗

bioRxiv2018

Effects of BMP-2 dose and delivery of microvascular fragments on healing of bone defects with concomitant volumetric muscle loss

Traumatic composite bone-muscle injuries, such as open fractures, often require multiple surgical interventions and still typically result in long-term disability. Clinically, a critical indicator of composite injury severity is vascular integrity; vascular damage alone is sufficient to assign an open fracture to the most severe category. Challenging bone injuries are often treated with bone morphogenetic protein 2 (BMP-2), an osteoinductive growth factor, delivered on collagen sponge. Previous studies in a composite defect model found that a minimally bridging dose in the segmental defect model was unable to overcome concomitant muscle damage, but the effect of BMP dose on composite injuries has not yet been studied. Here, we test the hypotheses that BMP-2-mediated functional regeneration of composite extremity injuries is dose dependent and can be further enhanced via co-delivery of adipose-derived microvascular fragments (MVF), which have been previously shown to increase tissue vascular volume. Although MVF treatment did not improve healing outcomes, we observed a significant BMP-2 dose-dependent increase in regenerated bone volume and biomechanical properties. While high dose BMP-2 delivery can induce heterotopic ossification (HO) and increased inflammation, the maximum 10 g dose used in this study did not result in HO and was associated with a lower circulating inflammatory cytokine profile than the low dose (2.5 g) group. These data support the potential benefits of an increased, though still moderate, BMP-2 dose for treatment of bone defects with concomitant muscle damage. Future work to improve vascularization may further improve healing.

bioengineering↗