Biology subjects

Snyder, L.

Publications and source records attributed to Snyder, L..

5 recordsLinked to original sources

bioRxiv2025

A multi-modal whole-slide image processing pipeline for quantitative mapping of tissue architecture, histopathology, and tissue microenvironment

Multi-modal, multiscale imaging is crucial for quantitative high-content spatial profiling. We present an integrated image processing pipeline for comprehensive tissue analysis that combines quantitative phase microscopy for tissue architecture mapping, hyper-plex fluorescence imaging for immune microenvironment profiling, and whole-slide histopathology. This approach enables detailed morphological mapping of tissue architecture and cell morphology, while simultaneously linking them to the functional states of individual cells across the entire slide. By analyzing tissue biopsies from patients with ulcerative colitis, we demonstrate the potential of this pipeline for quantitative spatial analysis of molecular markers related to mucosal healing. Open-source and compatible with conventional microscopy systems, this pipeline provides a powerful tool for research and clinical applications through its comprehensive integration of quantitative, high-content, and histological imaging modalities.

bioinformatics↗

bioRxiv2025

Simons Sleep Project (SSP): An open science resource for accelerating scalable digital health research in autism and other psychiatric conditions

Wearable and nearable devices offer a novel opportunity to measure extensive behavioral and neurophysiological data directly from participants in their home environment. The Simons Sleep Project (SSP) was designed to accelerate research into sleep and daily behaviors in individuals with autism using such techniques. This open-science resource contains raw and processed data from Dreem3 EEG headbands, multi-sensor EmbracePlus smartwatches, and Withings Sleep mats, as well as parent questionnaires and daily sleep diaries. Data were collected successfully for >3600 days/nights from 102 adolescents (10-17 years old) with idiopathic autism and 98 of their non-autistic siblings. Whole-exome sequencing data is also available for all participants and their parents. To demonstrate the utility of this extensive dataset, we first present the breadth of synchronized high-resolution data available across multiple sensors/devices. We then demonstrate that objective sleep measures (e.g., total sleep time) from the three devices are more accurate and reliable than parent reported measures and reveal that sleep onset latency (SOL) was the only objectively defined sleep measure that differed significantly between autistic children and their siblings (of those examined in the study). Moreover, SOL was reliably associated with the severity of multiple behavioral difficulties in all children, regardless of autism diagnosis. These results highlight the importance of measuring sleep directly from participants using objective measures and demonstrate the extensive opportunities afforded by the SSP to further study autism and develop new digital phenotyping techniques for multiple research domains.

neuroscience↗

bioRxiv2024

Sensorimotor faculties bias perceptual decision-making

Decision-making is a deliberate process that seemingly evolves under our own volition. Yet, research on embodied cognition has demonstrated that higher-order cognitive processes may be influenced, in unexpected ways, by properties of motor and sensory systems. Here we tested whether and how simple decisions are influenced by handedness and by asymmetries in the auditory system. Right- and left-handed participants performed an auditory decision task. In the task, subjects decided whether they heard more click sounds in the right ear or in the left ear, and pressed a key with either their right or left index finger, according to an instructed stimulus-key assignment (congruent or reversed). On some trials, there was no stimulus and subjects could choose either of the responses freely. When subjects chose freely, their choices were substantially governed by their handedness: Left-handed subjects were significantly biased to make the leftward choice, whereas right-handed subjects showed a substantial rightward bias. When the choice was governed by the sensory stimulus, subjects showed a rightward choice bias under the congruent key assignment, but this effect reversed to a leftward choice bias under the reversed key assignment. This result indicates a bias towards deciding that there were more clicks presented to the right ear. Together, our findings demonstrate that human choices can be considerably influenced by properties of motor and sensory systems.

neuroscience↗

bioRxiv2023

Evaluating functional brain organization in individuals and identifying contributions to network overlap

Individual differences in the spatial organization of resting state networks have received increased attention in recent years. Measures of individual-specific spatial organization of brain networks and overlapping network organization have been linked to important behavioral and clinical traits and are therefore potential biomarker targets for personalized psychiatry approaches. To better understand individual-specific spatial brain organization, this paper addressed three key goals. First, we determined whether it is possible to reliably estimate weighted (non-binarized) resting state network maps using data from only a single individual, while also maintaining maximum spatial correspondence across individuals. Second, we determined the degree of spatial overlap between distinct networks, using test-retest and twin data. Third, we systematically tested multiple hypotheses (spatial mixing, temporal switching, and coupling) as candidate explanations for why networks overlap spatially. To estimate weighted network organization, we adopt the Probabilistic Functional Modes (PROFUMO) algorithm, which implements a Bayesian framework with hemodynamic and connectivity priors to supplement optimization for spatial sparsity/independence. Our findings showed that replicable individual-specific estimates of weighted resting state networks can be derived using high quality fMRI data within individual subjects. Network organization estimates using only data from each individual subject closely resembled group-informed network estimates (which was not explicitly modeled in our individual-specific analyses), suggesting that cross-subject correspondence was largely maintained. Furthermore, our results confirmed the presence of spatial overlap in network organization, which was replicable across sessions within individuals and in monozygotic twin pairs. Intriguingly, our findings provide evidence that network overlap is indicative of linear additive coupling. These results suggest that regions of network overlap concurrently process information from all contributing networks, potentially pointing to the role of overlapping network organization in the integration of information across multiple brain systems.

neuroscience↗

bioRxiv2019

RNAseq studies reveal distinct transcriptional response to vitamin A deficiency in small intestine versus colon, discovering novel VA-regulated genes

Vitamin A (VA) deficiency remains prevalent in resource limited countries, affecting over 250 million preschool aged children. Vitamin A deficiency is associated with reduced intestinal barrier function and increased risk of mortality due to mucosal infection. Using Citrobacter rodentium (C. rodentium) infection in mice as a model for diarrheal diseases in humans, previous reports showed reduced pathogen clearance and survival in vitamin A deficient (VAD) mice compared to their vitamin A sufficient (VAS) counterparts. ObjectivesTo characterize and compare the impact of preexisting VA deficiency on gene expression patterns in the small intestine (SI) and the colon, and to discover novel target genes in VA-related biological pathways. MethodsVAD mice were generated by feeding VAD diet to pregnant C57/BL6 dams and their post-weaning offspring. RNAseq were performed using the total mRNAs extracted from SI and colon. Differentially Expressed Gene (DEG), Gene Ontology (GO) enrichment, and Weighted Gene Co-expression Network Analysis (WGCNA) were performed to characterize expression and co-expression patterns. ResultsDEGs compared between VAS and VAD groups detected 49 SI and 94 colon genes. By GO information, SI DEGs were significantly enriched in categories relevant to retinoid metabolic process, molecule binding, and immune function. Immunity related pathways, including "humoral immune response" and "complement activation" were positively associated with VA in SI. Three co-expression modules showed significant correlation with VA status in SI; these modules contained four known retinoic acid targets. In addition, other SI genes of interest (e.g. Mbl2, Cxcl14, and Nr0b2) in these modules were suggested as new candidate genes regulated by VA. Furthermore, our analysis showed that markers of two cell types in SI, mast cells and Tuft cells, were significantly altered by VA status. In colon, "cell division" was the only enriched category and was negatively associated with VA. Thus, comparison of co-expression modules between SI and colon indicated distinct networks under the regulation of dietary VA and suggest that preexisting VAD could have a significant impact on the host response to a variety of disease conditions.

physiology↗