Biology subjects

Lin, C.-H.

Publications and source records attributed to Lin, C.-H..

5 recordsLinked to original sources

bioRxiv2018

Using optically-pumped magnetometers to measure magnetoencephalographic signals in the human cerebellum

We test the feasibility of an optically pumped magnetometer (OPM)-MEG system for the measurement of human cerebellar activity. We show that the OPM system allows for excellent coverage of this structure by decreasing the average sensor-to-cerebellum distance by around 33% (16mm), compared to a standard MEG helmet. This closer proximity to the cerebellum approximately doubles the signal-to-noise ratio (SNR). As a proof of principle, we used an air-puff stimulus to the eyeball in order to elicit cerebellar evoked and induced responses that are well characterized in non-human models. In three subjects, we observed an evoked component at 50ms post stimulus, which originates in the cerebellum (predominantly ipsilateral). This response was followed by a second component at 100ms post stimulus (predominantly contra-lateral). Sensory stimulation also elicited an event-related broadband spectral power change in the ipsilateral cerebellum at ~100ms in all subjects. We conclude that the OPM-MEG technology offers a promising way to advance the understanding of the information processing mechanisms in the human cerebellum.

neuroscience↗

bioRxiv2018

Automated literature mining and hypothesis generation through a network of Medical Subject Headings

The scientific literature is vast, growing, and increasingly specialized, making it difficult to connect disparate observations across subfields. To address this problem, we sought to develop automated hypothesis generation by networking at scale the MeSH terms curated by the National Library of Medicine. The result is a Mesh Term Objective Reasoning (MeTeOR) approach that tallies associations among genes, drugs and diseases from PubMed and predicts new ones.\n\nComparisons to reference databases and algorithms show MeTeOR tends to be more reliable. We also show that many predictions based on the literature prior to 2014 were published subsequently. In a practical application, we validated experimentally a surprising new association found by MeTeOR between novel Epidermal Growth Factor Receptor (EGFR) associations and CDK2. We conclude that MeTeOR generates useful hypotheses from the literature (http://meteor.lichtargelab.org/).\n\nAUTHOR SUMMARYThe large size and exponential expansion of the scientific literature forms a bottleneck to accessing and understanding published findings. Manual curation and Natural Language Processing (NLP) aim to address this bottleneck by summarizing and disseminating the knowledge within articles as key relationships (e.g. TP53 relates to Cancer). However, these methods compromise on either coverage or accuracy, respectively. To mitigate this compromise, we proposed using manually-assigned keywords (MeSH terms) to extract relationships from the publications and demonstrated a comparable coverage but higher accuracy than current NLP methods. Furthermore, we combined the extracted knowledge with semi-supervised machine learning to create hypotheses to guide future work and discovered a direct interaction between two important cancer genes.

bioinformatics↗

bioRxiv2018

Polypyrimidine Tract Binding Protein blocks microRNA-124 biogenesis to enforce its neuronal specific expression.

MicroRNA-124 is expressed in neurons, where it represses genes inhibitory for neuronal differentiation, including the RNA binding protein PTBP1. PTBP1 maintains non-neuronal splicing patterns of mRNAs that switch to neuronal isoforms upon neuronal differentiation. We find that pri-miR-124-1 is expressed in mouse embryonic stem cells (mESCs) where mature miR-124 is absent. PTBP1 binds to this precursor RNA upstream of the miRNA stem-loop to inhibit mature miR-124 expression in vivo, and DROSHA cleavage of pri-miR-124-1 in vitro. This new function for PTBP1 in repressing miR-124 biogenesis adds an additional regulatory loop to the already intricate interplay between these two molecules. Applying mathematical modeling to examine the dynamics of this regulation, we find that the pool of pri-miR-124 whose maturation is blocked by PTBP1 creates a robust and self-reinforcing transition in gene expression as PTBP1 is depleted during early neuronal differentiation. While interlocking regulatory loops are often modeled between miRNAs and transcriptional regulators, our results indicate that miRNA targeting of posttranscriptional regulators also reinforces developmental decisions. Notably, induction of neuronal differentiation observed upon PTBP1 knockdown likely results from direct de-repression of miR-124, in addition to indirect effects previously described.

molecular biology↗

bioRxiv2018

Standardized Informatics Computing Platform for Advancing Biomedical Discovery Through Data Sharing

ObjectiveThe goal is to develop a standardized informatics computing system that can support end-to-end research data lifecycle management for biomedical research applications.\n\nMaterials and MethodsDesign and implementation of biomedical research informatics computing system (BRICS) is demonstrated. The system architecture is modular in design with several integrated tools: global unique identifier, validation, upload, download and query tools that support user friendly informatics system capability.\n\nResultsBRICS instances were deployed to support research for improvements in diagnosis of traumatic brain injury, biomarker discovery for Parkinsons Disease, the National Ophthalmic Disease Genotyping and Phenotyping network, the informatics core for the Center for Neuroscience and Regenerative Medicine, the Common Data Repository for Nursing Science, Global Rare Diseases Patient Registry, and National Institute of Neurological Disorders and Stroke Clinical Informatics system for trials and research.\n\nDiscussionData deidentification is conducted by using global unique identifier methodology. No personally identifiable information exists on the BRICS supported repositories. The Data Dictionary provides defined Common Data Elements and Unique Data Elements, specific to each of the BRICS instance that enables Query Tool to search through research data. All instances are supported by the Medical Imaging Processing, statistical analysis R, and Visualization software program.\n\nConclusionThe BRICS core modules can be easily adapted for various biomedical research needs thereby reducing cost in developing new instances for additional biomedical research needs. It provides user friendly tools for researchers to query and aggregate genetic, phenotypic, clinical and medical imaging data. Data sets are findable, accessible and reusable for researchers to foster new research on various diseases.

bioinformatics↗

bioRxiv2017

The role of sensorimotor variability and computation in falls in the elderly

The relationship between sensorimotor variability and falls in elderly has not been well investigated. We designed and used a motor task having shared biomechanics of walking and obstacle negotiation to quantify sensorimotor variability related to locomotion across age. We also applied sensory psychophysics to pinpoint specific sensory systems associated with sensorimotor variability. We found that sensorimotor variability in foot placement increases continuously with age. We further showed that increased sensory variability, specifically increased proprioceptive variability, the vital cause of more variable foot placement in the elderly. Notably, elderly participants relied more on the vision to judge their own foots height compared to the young, suggesting a shift in multisensory integration strategy to compensate for degenerated proprioception. We further modelled the probability of tripping-over based on the relationship between sensorimotor variability and age and found a good correspondence between model prediction and community-based data. We revealed increased sensorimotor variability, modulated by sensation precision, a potentially vital mechanism of raised tripping-over and thus fall events in the elderly. Therefore, our tasks, which quantify sensorimotor variability, can be used for trip-over probability assessment and, with adjustments, potentially applied as a training program to mitigate trip-over risk.

neuroscience↗