Gene noise

Epidemiological studies have found that transportation noise increases the risk for cardiovascular morbidity and mortality, with solid evidence for ischemic heart disease, heart failure, and stroke. According to the World Health Organization, at least 1.6 million healthy life years are lost annually from traffic-related noise in Western Europe. Traffic noise at night causes fragmentation and shortening of sleep, elevation of stress hormone levels, and increased oxidative stress in the vasculature and the brain...

Human induced pluripotent stem cells (hiPSCs) are frequently used to study disease-associated variations. We characterized transcriptional variability from a hiPSC-derived cardiomyocyte (hiPSC-CM) study of left ventricular hypertrophy (LVH) using donor samples from the HyperGEN study. Multiple hiPSC-CM differentiations over reprogramming events (iPSC generation) across 7 donors were used to assess variabilities from reprogramming, differentiation, and donor LVH status. Variability arising from pathological alterations was assessed using a cardiac stimulant applied to the hiPSC-CMs to trigger hypertrophic responses...

Single-cell/nuclei RNA sequencing (sc/snRNA-Seq) is widely used for profiling cell-type gene expressions in biomedical research. An important but underappreciated issue is the quality of sc/snRNA-Seq data that would impact the reliability of downstream analyses. Here we evaluated the precision and accuracy in 18 sc/snRNA-Seq datasets. The precision was assessed on data from human brain studies with a total of 3,483,905 cells from 297 individuals, by utilizing technical replicates. The accuracy was evaluated with sample-matched scRNA-Seq and pooled-cell RNA-Seq data of cultured mononuclear phagocytes from four species...

Acoustic communication plays important roles in the survival and reproduction of anurans. The perception and discrimination of conspecific sound signals of anurans were always affected by masking background noise. Previous studies suggested that some frogs evolved the high-frequency hearing to minimize the low-frequency noise. However, the molecular mechanisms underlying the high-frequency hearing in anurans have not been well explored. Here, we cloned and obtained the coding regions of a high-frequency hearing-related gene ( KCNQ4 ) from 11 representative anuran species and compared them with orthologous sequences from other four anurans...

Various studies have linked several diseases, including cancer and COVID-19, to single nucleotide variations (SNV). Although single-cell RNA sequencing (scRNA-seq) technology can provide SNV and gene expression data, few studies have integrated and analyzed these multimodal data. To address this issue, we introduce Interpretable Single-cell Multimodal Data Integration Based on Variational Autoencoder (ISMI-VAE). ISMI-VAE leverages latent variable models that utilize the characteristics of SNV and gene expression data to overcome high noise levels and uses deep learning techniques to integrate multimodal information, map them to a low-dimensional space, and classify disease cells...

Organisms utilize gene regulatory networks (GRN) to make fate decisions, but the regulatory mechanisms of transcription factors (TF) in GRNs are exceedingly intricate. A longstanding question in this field is how these tangled interactions synergistically contribute to decision-making procedures. To comprehensively understand the role of regulatory logic in cell fate decisions, we constructed a logic-incorporated GRN model and examined its behavior under two distinct driving forces (noise-driven and signal-driven)...

BACKGROUND: Accurately deciphering clonal copy number substructure can provide insights into the evolutionary mechanism of cancer, and clustering single-cell copy number profiles has become an effective means to unmask intra-tumor heterogeneity (ITH). However, copy numbers inferred from single-cell DNA sequencing (scDNA-seq) data are error-prone due to technically confounding factors such as amplification bias and allele-dropout, and this makes it difficult to precisely identify the ITH...

Spatial transcriptome technologies have enabled the measurement of gene expression while maintaining spatial location information for deciphering the spatial heterogeneity of biological tissues. However, they were heavily limited by the sparse spatial resolution and low data quality. To this end, we develop a spatial location-supervised auto-encoder generator STAGE for generating high-density spatial transcriptomics (ST). STAGE takes advantage of the customized supervised auto-encoder to learn continuous patterns of gene expression in space and generate high-resolution expressions for given spatial coordinates...

Regenerative potential is governed by a complex process of transcriptional reprogramming, involving chromatin reorganization and dynamics in transcription factor binding patterns throughout the genome. The degree to which chromatin and epigenetic changes contribute to this process remains partially understood. Here we provide a modified CUT&Tag protocol suitable for improved characterization and interrogation of epigenetic changes during adult fin regeneration in zebrafish. Our protocol generates data that recapitulates results from previously published ChIP-Seq methods, requires far fewer cells as input, and significantly improves signal to noise ratios...

Magnetic nanoparticles can be used as a targeted delivery vehicle for genetic therapies. Understanding how they can be manipulated within the complex environment of live airways is key to their application to cystic fibrosis and other respiratory diseases.
Approach: Dark-field X-ray imaging provides sensitivity to scattering information, and allows the presence of structures smaller than the detector pixel size to be detected. In this study, ultrafast directional dark-field synchrotron X-ray imaging was utlilised to understand how magnetic nanoparticles move within a live, anaesthetised, rat airway under the influence of static and moving
magnetic fields...

Precise control of gene expression levels is essential for normal cell functions, yet how they are defined and tightly maintained, particularly at intermediate levels, remains elusive. Here, using a series of newly developed sequencing, imaging, and functional assays, we uncover a class of transcription factors with dual roles as activators and repressors, referred to as condensate-forming level-regulating dual-action transcription factors (TFs). They reduce high expression but increase low expression to achieve stable intermediate levels...

Spatial transcriptomics (ST) has become a powerful tool for exploring the spatial organization of gene expression in tissues. Imaging-based methods, though offering superior spatial resolutions at the single-cell level, are limited in either the number of imaged genes or the sensitivity of gene detection. Existing approaches for enhancing ST rely on the similarity between ST cells and reference single-cell RNA sequencing (scRNA-seq) cells. In contrast, we introduce stDiff, which leverages relationships between gene expression abundance in scRNA-seq data to enhance ST...

MOTIVATION: With the rapid advancement of single-cell sequencing technology, it becomes gradually possible to delve into the cellular responses to various external perturbations at the gene expression level. However, obtaining perturbed samples in certain scenarios may be considerably challenging, and the substantial costs associated with sequencing also curtail the feasibility of large-scale experimentation. A repertoire of methodologies has been employed for forecasting perturbative responses in single-cell gene expression...

Rosenberg et al. (2022) recently found a surprising correlation between synonymous codon usage and the dihedral bond angles of the resulting amino acid. However, their analysis did not account for the strongest known correlate of codon usage: gene expression. We re-examined the relationship between bond angles and codon usage by applying the approach of Rosenberg et al. to simulated protein-coding sequences that (1) have random codon usage, (2) codon usage determined by mutation biases, and (3) maintain the general relationship between codon usage and gene expression via the assumption of selection-mutation-drift equilibrium...

In profiling assays, thousands of biological properties are measured in a single test, yielding biological discoveries by capturing the state of a cell population, often at the single-cell level. However, for profiling datasets, it has been challenging to evaluate the phenotypic activity of a sample and the phenotypic consistency among samples, due to profiles' high dimensionality, heterogeneous nature, and non-linear properties. Existing methods leave researchers uncertain where to draw boundaries between meaningful biological response and technical noise...

Identifying hidden states in nonlinear physical systems that evade direct experimental detection is important as disturbances and noises can place the system in a hidden state with detrimental consequences. We study a cavity magnonic system whose main physics is photon and magnon Kerr effects. Sweeping a bifurcation parameter in numerical experiments (as would be done in actual experiments) leads to a hysteresis loop with two distinct stable steady states, but analytic calculation gives a third folded steady state "hidden" in the loop, which gives rise to the phenomenon of hidden multistability...

Bacteria-based therapies are powerful strategies for cancer therapy, yet their clinical application is limited by a lack of tunable genetic switches to safely regulate the local expression and release of therapeutic cargoes. Rapid advances in remote-control technologies have enabled precise control of biological processes in time and space. We developed therapeutically active engineered bacteria mediated by a sono-activatable integrated gene circuit based on the thermosensitive transcriptional repressor TlpA39 ...

By generating massive gene transcriptome data and analyzing transcriptomic variations at the cell level, single-cell RNA-sequencing (scRNA-seq) technology has provided new way to explore cellular heterogeneity and functionality. Clustering scRNA-seq data could discover the hidden diversity and complexity of cell populations, which can aid to the identification of the disease mechanisms and biomarkers. In this paper, a novel method (DSINMF) is presented for single cell RNA sequencing data by using deep matrix factorization...

BACKGROUND: The relationship between CDH23 gene variants and NIHL is unclear. This study investigates the association between cadherin 23 ( CDH23 ) gene variants and noise-induced hearing loss (NIHL). METHODS: This is a case-control study. Workers who were exposed to noise from a steel factory in North China were recruited and divided into two groups: the case group (both ears' high-frequency threshold average [BHFTA] ≥40dB) and the control group (BHFTA ≤25 dB)...

Gene regulatory network (GRN) comprises complicated yet intertwined gene-regulator relationships. Understanding the GRN dynamics will unravel the complexity behind the observed gene expressions. Insect gene regulation is often complicated due to their complex life cycles and diverse ecological adaptations. The main interest of this review is to have an update on the current mathematical modelling methods of GRNs to explain insect science. Several popular GRN architecture models are discussed, together with examples of applications in insect science...