Biology subjects

Wang, J.-P.

Publications and source records attributed to Wang, J.-P..

10 recordsLinked to original sources

bioRxiv2025

Differential nucleosome organization in human interphase and metaphase chromosomes

DNA bendability plays a critical role in stabilizing nucleosome assembly, yet its contribution to nucleosome dynamics in vivo remains poorly understood. Here, we applied chemical mapping to generate high-resolution nucleosome positioning maps at single-base-pair resolution from human interphase and metaphase chromosomes, revealing distinct patterns of nucleosome organization between the two states. Notably, we observed a unifying pattern of nucleosome positioning near euchromatic landmarks, including promoters, enhancers, and insulators, during mitosis. Interphase nucleosomes exhibited extensive repositioning, marked by increased nucleosome density, reduced spacing between nucleosomes, and the appearance of additional fragile nucleosomes compared to metaphase. Furthermore, our results show that metaphase nucleosomes display significantly higher DNA cyclizability around the dyad axis, whereas interphase nucleosomes, particularly those near regulatory regions, tend to position DNA with greater cyclizability at the edges of the nucleosome. Together, these findings highlight a dynamic interplay between DNA mechanics and nucleosome organization during the cell cycle.

genomics↗

bioRxiv2024

Integrating genetic and gene expression data in network-based stratification analysis of cancers

Cancers are complex diseases that have heterogeneous genetic drivers and varying clinical outcomes. A critical area of cancer research is organizing patient cohorts into subtypes and associating subtypes with clinical and biological outcomes for more effective prognosis and treatment. Large-scale studies have collected a plethora of omics data across multiple tumor types. These studies provide an extensive dataset for stratifying patient cohorts. Network-based stratification (NBS) approaches have been presented to classify cancer tumors using somatic mutation data. A challenge in cancer stratification is integrating omics data to yield clinically meaningful subtypes. In this study, we integrate somatic mutation data with RNA sequencing data within the NBS framework and investigate the effectiveness of integrated NBS on three cancers: ovarian, bladder, and uterine cancer. We show that integrated NBS subtypes are more significantly associated with overall survival or histology. Integrated NBS networks also reveal highly influential genes that drive cancer initiation and progression. This comprehensive approach underscores the significance of integrating genomic data types in cancer subtyping, offering profound implications for personalized prognosis and treatment strategies.

systems biology↗

bioRxiv2024

NLSDeconv: an efficient cell-type deconvolution method for spatial transcriptomics data

SummarySpatial transcriptomics (ST) allows gene expression profiling within intact tissue samples but lacks single-cell resolution. This necessitates computational deconvolution methods to estimate the contributions of distinct cell types. This paper introduces NLSDeconv, a novel cell-type deconvolution method based on non-negative least squares, along with an accompanying Python package. Benchmarking against 18 existing deconvolution methods on various ST datasets demonstrates NLSDeconvs competitive statistical performance and superior computational efficiency. Availability and implementationNLSDeconv is freely available with tutorial at https://github.com/tinachentc/NLSDeconv as a Python package.

genomics↗

bioRxiv2023

Portable Arbitrary Pulse Generator for Driving μCoils for Micromagnetic Neurostimulation

Micromagnetic stimulation (MS) is a promising branch of neurostimulation technologies. Microcoil (coil) based magnetic stimulation uses micrometer sized coils that generate a time-varying magnetic field which as per Faradays Laws of Electromagnetic Induction induces an electric field on a conductive surface. This method of stimulation has the advantage of not requiring electrical contact with tissue, however these coils are not easy to operate. Large currents are required to generate the required magnetic field. These currents are too large for standard test equipment to provide, and additional power amplifiers are needed. To aid in the development and application of micromagnetic stimulation devices, we have created a compact single unit test setup for driving these devices called the Coil Driver. This unit is designed to drive small inductive loads up to {+/-}8 V at 5 A and 10 kHz.

neuroscience↗

bioRxiv2023

Micromagnetic Stimulation (μMS) Controls Dopamine Release: An in vivo Study Using WINCS Harmoni

ObjectiveResearch into the role of neurotransmitters in regulating normal and pathologic brain functions has made significant progress. Yet, clinical trials that aim to improve therapeutic interventions do not take advantage of the in vivo changes in the neurochemistry that occur in real time during disease progression, drug interactions or response to pharmacological, cognitive, behavioral, and neuromodulation therapies. In this work, we used the WINCS Harmoni tool to study the real time in vivo changes in dopamine release in rodent brains for the micromagnetic neuromodulation therapy. ApproachAlthough still in its infancy, micromagnetic stimulation (MS) using micro-meter sized coils or microcoils (coils) has shown incredible promise in spatially selective, galvanic contact free and highly focal neuromodulation. These coils are powered by a time-varying current which generates a magnetic field. As per Faradays Laws of Electromagnetic Induction, this magnetic field induces an electric field in a conducting medium (here, the brain tissues). We used a solenoidal-shaped coil to stimulate the medial forebrain bundle (MFB) of the rodent brain in vivo. The evoked in vivo dopamine releases in the striatum were tracked in real time by carbon fiber microelectrodes (CFM) using fast scan cyclic voltammetry (FSCV). ResultsOur experiments report that coils can successfully activate the MFB in rodent brains, triggering dopamine release in vivo. We further show that the successful release of dopamine upon micromagnetic stimulation is dependent on the orientation of the coil. Furthermore, varied intensities of MS can control the concentration of dopamine releases in the striatum. SignificanceThis work helps us better understand the brain and its conditions arising from a new therapeutic intervention, like MS, at the level of neurotransmitter release. Despite its early stage, this study potentially paves the path for MS to enter the clinical world as a precisely controlled and optimized neuromodulation therapy.

neuroscience↗

bioRxiv2023

Hematopoietic Transfer of the Anti-Cancer and Lifespan-Extending Capabilities of A Genetically Engineered Blood System

A causal relationship exists among the aging process, organ decay and dis-function, and the occurrence of various diseases including cancer. A genetically engineered mouse model, termed Klf1K74R/K74R or Klf1(K74R), carrying mutation on the well-conserved sumoylation site of the hematopoietic transcription factor KLF1/ EKLF has been generated that possesses extended lifespan and healthy characteristics including cancer resistance. We show that the healthy longevity characteristics of the Klf1(K74R) mice, as exemplified by their higher anti- cancer capability, are likely gender-, age- and genetic background-independent. Significantly, the anti-cancer capability, in particular that against melanoma as well as hepatocellular carcinoma, and lifespan-extending property of Klf1(K74R) mice could be transferred to wild-type mice via transplantation of their bone marrow mononuclear cells at young age of the latter. Furthermore, NK(K74R) cells carry higher in vitro cancer cell-killing ability than wild type NK cells. Targeted/global gene expression profiling analysis has identified changes of the expression of specific proteins, including the immune checkpoint factors PDCD and CD274, and cellular pathways in the leukocytes of the Klf1(K74R) that are in the directions of anti-cancer and/or anti-aging. This study demonstrates the feasibility of developing a transferable hematopoietic/ blood system for long-term anti-cancer and, potentially, for anti-aging.

cancer biology↗

bioRxiv2022

Micromagnetic Stimulation (μMS) Dose-Response of the Rat Sciatic Nerve

ObjectiveThe objective of this study was to investigate the effects of micromagnetic stimuli strength and frequency from the Magnetic Pen (MagPen) on the rat right sciatic nerve. The nerves response would be measured by recording muscle activity and movement of the right hind limb. ApproachThe MagPen was custom-built such that it can be held over the sciatic nerve in a stable manner. Rat leg muscle twitches were captured on video and movements were extracted using image processing algorithms. EMG recordings were also used to measure muscle activity. Main resultsThe MagPen prototype when driven by alternating current, generates time-varying magnetic field which as per Faradays Law of Electromagnetic Induction, induces an electric field for neuromodulation. The orientation dependent spatial contour maps for the induced electric field from the MagPen prototype has been numerically simulated. Furthermore, in this in vivo work on MS, a dose-response relationship has been reported by experimentally studying how the varying amplitude (Range: 25 mVp-p through 6 Vp-p) and frequency (Range: 100 Hz through 5 kHz) of the MagPen stimuli alters the hind limb movement. The primary highlight of this dose-response relationship is that at a higher frequency of the MS stimuli, significantly smaller amplitudes can trigger hind limb muscle twitch. This frequency-dependent activation can be justified following directly from the Faradays Law as the magnitude of the induced electric field is directly proportional to frequency. SignificanceThis work reports that MS can successfully activate the sciatic nerve in a dose-dependent manner. The MagPen probe, unlike electrodes, does not have a direct electrochemical interface with tissues rendering it much safer than an electrode. Magnetic fields create more precise activation than electrodes because they induce smaller volumes of activation. Finally, unique features of MS such as orientation dependence, directionality and spatial selectivity have been demonstrated.

bioengineering↗

bioRxiv2021

Strength-frequency curve for micromagnetic neurostimulation through EPSPs on rat hippocampal neurons and numerical modeling of magnetic microcoil (μcoil)

ObjectiveThe objective of this study was to measure the effect of micromagnetic stimulation (MS) on hippocampal neurons, by using single microcoil (coil) prototype, Magnetic Pen (MagPen). MagPen will be used to stimulate the CA3 region magnetically and excitatory post synaptic potential (EPSP) response measurements will be made from the CA1 region. The threshold for micromagnetic neurostimulation as a function of stimulation frequency of the current driving the coil will be demonstrated. Finally, the optimal stimulation frequency of the current driving the coil to minimize power will be estimated. ApproachA biocompatible, watertight, non-corrosive prototype, MagPen was built, and customized such that it is easy to adjust the orientation of the coil and its distance over the hippocampal tissue in an in vitro recording setting. Finite element modeling (FEM) of the coil design was performed to estimate the spatial profiles of the magnetic flux density (in T) and the induced electric fields (in V/m). The induced electric field profiles generated at different values of current applied to the coil can elicit a neuron response, which was validated by numerical modeling. The modeling settings for the coil were replicated in experiments on rat hippocampal neurons. Main resultsThe preferred orientation of MagPen over the Schaffer Collateral fibers was demonstrated such that they elicit a neuron response. The recorded EPSPs from CA1 region due to MS at CA3 region were validated by applying tetrodotoxin (TTX). Application of TTX to the hippocampal slice blocked the EPSPs from MS while after prolonged TTX washout, a partial recovery of the EPSP from MS was observed. Finally, it was interpreted through numerical analysis that increasing frequency of the current driving the coil, led to a decrease in the current amplitude threshold for micromagnetic neurostimulation. SignificanceThis work reports that micromagnetic neurostimulation can be used to evoke population EPSP responses in the CA1 region of the hippocampus. It demonstrates the strengthfrequency curve for MS and its unique features related to orientation dependence of the coils, spatial selectivity and stimulation threshold related to distance dependence. Finally, the challenges related to MS experiments were studied including ways to overcome them.

bioengineering↗

bioRxiv2020

RiboDiPA: A novel tool for differential pattern analysis in Ribo-seq data

AO_SCPLOWBSTRACTC_SCPLOWRibosome profiling (also known as Ribo-seq) has become an important technique to investigate changes in translation across a wide variety of contexts. Ribo-seq data not only provides the abundance of ribosomes bound to transcripts, but also positional information across transcripts that could be indicative of differences in translation dynamics between conditions. While many computational tools exist for the analysis of Ribo-seq data, including those that assess differences in translational efficiency between conditions, no tool currently exists for rigorous test of the pattern differences in ribosome footprint. In this paper we propose a novel approach together with an R package, RiboDiPA, for Differential PPattern Analysis of Ribo-seq data. RiboDiPA allows for quick identification of genes with statistically significant differences in ribosome occupancy patterns for model organisms ranging from yeast to mammals. We show that differential pattern analysis reveals information that is distinct and complimentary to the existing methods that focus on translational efficiency analysis. Using both simulated Ribo-seq footprint data and two benchmark data sets, we illustrate that RiboDiPA can not only uncover meaningful global translational differences between conditions, but also the detailed differential ribosome binding patterns to a single codon resolution.

bioinformatics↗

bioRxiv2018

Normalization of generalized transcript degradation improves accuracy in RNA-seq analysis

RNA-seq is a high-throughput assay to profile transcriptional activities in cells. Here we show that transcript degradation is gene-/sample-specific and presents a common and major source that may substantially bias the results in RNA-seq analysis. Most existing global normalization approaches are ineffective to correct for the degradation bias. We propose a novel pipeline named DegNorm (stands for degradation normalization) to adjust read counts for transcript degradation heterogeneity on a gene-by-gene basis while simultaneously controlling the sequencing depth. The robust and effective performance of this method is demonstrated in an extensive set of real RNA-seq data and simulated data.

bioinformatics↗