Biology subjects

Sanchez, R. M.

Publications and source records attributed to Sanchez, R. M..

3 recordsLinked to original sources

bioRxiv2025

CryoSiam: self-supervised representation learning for automated analysis of cryo-electron tomograms

Cryo-electron tomography (cryo-ET) enables visualization of macromolecular complexes in their native cellular context, but interpretation remains challenging due to high noise levels, missing information, and lack of ground-truth data. Here, we present CryoSiam (CRYO-electron tomography SIAMese networks), an open-source framework for self-supervised representation learning in cryo-ET. CryoSiam learns hierarchical representations of tomographic data spanning both voxel-level and subtomogram-level information. To train CryoSiam, we generated CryoETSim (CRYO-Electron Tomography SIMulated), a synthetic dataset that systematically models defocus variation, sample thickness, and molecular crowding. CryoSiam trained models transfer directly to experimental data without fine-tuning and support key aspects of cryo-ET data analysis, including tomogram denoising, segmentation of subcellular structures, and macromolecular detection and identification across both prokaryotic and eukaryotic systems. Publicly available pretrained models and the CryoETSim dataset provide a foundation for scalable and automated cryo-ET analysis.

bioinformatics↗

bioRxiv2023

Streamlined Structure Determination by Cryo-Electron Tomography and Subtomogram Averaging using TomoBEAR

Structures of macromolecules in their native state provide unique unambiguous insights into their functions. Cryo-electron tomography combined with subtomogram averaging demonstrated the power to solve such structures in situ at resolutions in the range of 3 Angstrom for some macromolecules. In order to be applicable to structural determination of the majority of macromolecules observable in cells in limited amounts, processing of tomographic data has to be performed in a high-throughput manner. Here we present TomoBEAR - a modular configurable workflow engine for streamlined processing of cryo-electron tomographic data for subtomogram averaging. TomoBEAR combines commonly used cryo-EM packages and reasonable presets to provide a transparent "white box" for data management and processing. We demonstrate applications of TomoBEAR to two datasets of purified proteins and to a membrane protein RyR1 in a membrane and demonstrate the ability to produce high resolution with minimal human intervention. TomoBEAR is an open-source and extendable package, it will accelerate the adoption of in situ structural biology by cryo-ET.

biophysics↗

bioRxiv2018

Imaging human cortical responses to intraneural microstimulation using magnetoencephalography

The sensation of touch in the glabrous skin of the human hand is conveyed by thousands of fast-conducting mechanoreceptive afferents, which can be categorised into four distinct types. The spiking properties of these afferents in the periphery in response to varied tactile stimuli are well-characterised, but relatively little is known about the spatiotemporal properties of the neural representations of these different receptor types in the human cortex. Here, we use the novel methodological combination of single-unit intraneural microstimulation (INMS) with magnetoencephalography (MEG) to localise cortical representations of individual touch afferents in humans, by measuring the extracranial magnetic fields from neural currents. We found that by assessing the modulation of the beta (13-30 Hz) rhythm during single-unit INMS, significant changes in oscillatory amplitude occur in the contralateral primary somatosensory cortex within and across a group of fast adapting type I mechanoreceptive 20 afferents, which corresponded well to the induced response from matched vibrotactile stimulation. Combining the spatiotemporal specificity of MEG with the selective single-unit stimulation of INMS enables the interrogation of the central representations of different aspects of tactile afferent signalling within the human cortices. The fundamental finding that single-unit INMS ERD responses are robust and consistent with natural somatosensory stimuli will permit us to more dynamically probe the central nervous system responses in humans, to address questions about the processing of touch from the different classes of mechanoreceptive afferents and the effects of varying the stimulus frequency and patterning.

neuroscience↗