MetaDegron: multimodal feature-integrated protein language model for predicting E3 ligase targeted degrons.

Protein degradation through the ubiquitin proteasome system at the spatial and temporal regulation is essential for many cellular processes. E3 ligases and degradation signals (degrons), the sequences they recognize in the target proteins, are key parts of the ubiquitin-mediated proteolysis, and their interactions determine the degradation specificity and maintain cellular homeostasis. To date, only a limited number of targeted degron instances have been identified, and their properties are not yet fully characterized.

ImmuneApp for HLA-I epitope prediction and immunopeptidome analysis.

Advances in mass spectrometry accelerates the characterization of HLA ligandome, necessitating the development of efficient methods for immunopeptidomics analysis and (neo)antigen prediction. We develop ImmuneApp, an interpretable deep learning framework trained on extensive HLA ligand datasets, which improves the prediction of HLA-I epitopes, prioritizes neoepitopes, and enhances immunopeptidomics deconvolution. ImmuneApp extracts informative embeddings and identifies key residues for pHLA binding.

Scientific preparation for JRT: Wind pressure prediction model for large radio telescope based on real data from multi-sensors.

Jingdong 120-meter radio telescope (JRT) is poised to become the world's largest single-aperture fully steerable medium-low frequency radio telescope. However, like other large-aperture radio telescopes, the JRT is vulnerable to wind loads, which can cause structural deformation and pointing errors. Addressing this challenge requires the ability to predict dynamic winds in real-time.

LEUTX regulates porcine embryonic genome activation in somatic cell nuclear transfer embryos.

Emerging evidence highlights the regulatory role of paired-like (PRD-like) homeobox transcription factors (TFs) in embryonic genome activation (EGA). However, the majority of PRD-like genes are lost in rodents, thus prompting an investigation into PRD-like TFs in other mammals. Here, we showed that PRD-like TFs were transiently expressed during EGA in human, monkey, and porcine fertilized embryos, yet they exhibited inadequate expression in their cloned embryos.

Advances in functional lipid nanoparticles: from drug delivery platforms to clinical applications.

Since Doxil's first clinical approval in 1995, lipid nanoparticles have garnered great interest and shown exceptional therapeutic efficacy. It is clear from the licensure of two RNA treatments and the mRNA-COVID-19 vaccination that lipid nanoparticles have immense potential for delivering nucleic acids. The review begins with a list of lipid nanoparticle types, such as liposomes and solid lipid nanoparticles.

DegronMD: Leveraging Evolutionary and Structural Features for Deciphering Protein-Targeted Degradation, Mutations, and Drug Response to Degrons.

Protein-targeted degradation is an emerging and promising therapeutic approach. The specificity of degradation and the maintenance of cellular homeostasis are determined by the interactions between E3 ubiquitin ligase and degradation signals, known as degrons. The human genome encodes over 600 E3 ligases; however, only a small number of targeted degron instances have been identified so far.

A Framework for Detecting Thyroid Cancer from Ultrasound and Histopathological Images Using Deep Learning, Meta-Heuristics, and MCDM Algorithms.

Computer-assisted diagnostic systems have been developed to aid doctors in diagnosing thyroid-related abnormalities. The aim of this research is to improve the diagnosis accuracy of thyroid abnormality detection models that can be utilized to alleviate undue pressure on healthcare professionals. In this research, we proposed deep learning, metaheuristics, and a MCDM algorithms-based framework to detect thyroid-related abnormalities from ultrasound and histopathological images.

KLF4 facilitates chromatin accessibility remodeling in porcine early embryos.

Chromatin accessibility remodeling driven by pioneer factors is critical for the development of early embryos. Current studies have illustrated several pioneer factors as being important for agricultural animals, but what are the pioneer factors and how the pioneer factors remodel the chromatin accessibility in porcine early embryos is not clear. By employing low-input DNase-seq (liDNase-seq), we profiled the landscapes of chromatin accessibility in porcine early embryos and uncovered a unique chromatin accessibility reprogramming pattern during porcine preimplantation development.

Lipidomic Characterization of Oocytes at Single-Cell Level Using Nanoflow Chromatography-Trapped Ion Mobility Spectrometry-Mass Spectrometry.

Mass spectrometry (MS)-based lipidomic has become a powerful tool for studying lipids in biological systems. However, lipidome analysis at the single-cell level remains a challenge. Here, we report a highly sensitive lipidomic workflow based on nanoflow liquid chromatography and trapped ion mobility spectrometry (TIMS)-MS.

Dynamic Control of Contractile Force in Engineered Heart Tissue.

Unlabelled: Three-dimensional engineered heart tissues (EHTs) derived from human induced pluripotent stem cells (iPSCs) have become an important resource for both drug toxicity screening and research on heart disease. A key metric of EHT phenotype is the contractile (twitch) force with which the tissue spontaneously beats. It is well-known that cardiac muscle contractility - its ability to do mechanical work - depends on tissue prestrain (preload) and external resistance (afterload).

Rewired mA epitranscriptomic networks link mutant p53 to neoplastic transformation.

N6-methyladenosine (mA), one of the most prevalent mRNA modifications in eukaryotes, plays a critical role in modulating both biological and pathological processes. However, it is unknown whether mutant p53 neomorphic oncogenic functions exploit dysregulation of mA epitranscriptomic networks. Here, we investigate Li-Fraumeni syndrome (LFS)-associated neoplastic transformation driven by mutant p53 in iPSC-derived astrocytes, the cell-of-origin of gliomas.

Benchmark of embedding-based methods for accurate and transferable prediction of drug response.

Prediction of therapy response has been a major challenge in cancer precision medicine due to the extensive tumor heterogeneity. Recently, several deep learning methods have been developed to predict drug response by utilizing various omics data. Most of them train models by using the drug-response screening data generated from cell lines and then use these models to predict response in cancer patient data.

scGWAS: landscape of trait-cell type associations by integrating single-cell transcriptomics-wide and genome-wide association studies.

Background: The rapid accumulation of single-cell RNA sequencing (scRNA-seq) data presents unique opportunities to decode the genetically mediated cell-type specificity in complex diseases. Here, we develop a new method, scGWAS, which effectively leverages scRNA-seq data to achieve two goals: (1) to infer the cell types in which the disease-associated genes manifest and (2) to construct cellular modules which imply disease-specific activation of different processes.

Results: scGWAS only utilizes the average gene expression for each cell type followed by virtual search processes to construct the null distributions of module scores, making it scalable to large scRNA-seq datasets.

Coordination of zygotic genome activation entry and exit by H3K4me3 and H3K27me3 in porcine early embryos.

Histone modifications are critical epigenetic indicators of chromatin state associated with gene expression. Although the reprogramming patterns of H3K4me3 and H3K27me3 have been elucidated in mouse and human preimplantation embryos, the relationship between these marks and zygotic genome activation (ZGA) remains poorly understood. By ultra-low-input native chromatin immunoprecipitation and sequencing, we profiled global H3K4me3 and H3K27me3 in porcine oocytes and in vitro fertilized (IVF) embryos.

Hierarchical Accumulation of Histone Variant H2A.Z Regulates Transcriptional States and Histone Modifications in Early Mammalian Embryos.

Early embryos undergo extensive epigenetic reprogramming to achieve gamete-to-embryo transition, which involves the loading and removal of histone variant H2A.Z on chromatin. However, how does H2A.

WebCSEA: web-based cell-type-specific enrichment analysis of genes.

Human complex traits and common diseases show tissue- and cell-type- specificity. Recently, single-cell RNA sequencing (scRNA-seq) technology has successfully depicted cellular heterogeneity in human tissue, providing an unprecedented opportunity to understand the context-specific expression of complex trait-associated genes in human tissue-cell types (TCs). Here, we present the first web-based application to quickly assess the cell-type-specificity of genes, named Web-based Cell-type Specific Enrichment Analysis of Genes (WebCSEA, available at https://bioinfo.

Hereditary retinoblastoma iPSC model reveals aberrant spliceosome function driving bone malignancies.

The RB1 gene is frequently mutated in human cancers but its role in tumorigenesis remains incompletely defined. Using an induced pluripotent stem cell (iPSC) model of hereditary retinoblastoma (RB), we report that the spliceosome is an up-regulated target responding to oncogenic stress in RB1-mutant cells. By investigating transcriptomes and genome occupancies in RB iPSC–derived osteoblasts (OBs), we discover that both E2F3a, which mediates spliceosomal gene expression, and pRB, which antagonizes E2F3a, coregulate more than one-third of spliceosomal genes by cobinding to their promoters or enhancers.

Angiogenic gene networks are dysregulated in opioid use disorder: evidence from multi-omics and imaging of postmortem human brain.

Opioid use disorder (OUD) is a public health crisis in the U.S. that causes over 50 thousand deaths annually due to overdose.

Genome-Wide Correlation of DNA Methylation and Gene Expression in Postmortem Brain Tissues of Opioid Use Disorder Patients.

Background: Opioid use disorder (OUD) affects millions of people, causing nearly 50 000 deaths annually in the United States. While opioid exposure and OUD are known to cause widespread transcriptomic and epigenetic changes, few studies in human samples have been conducted. Understanding how OUD affects the brain at the molecular level could help decipher disease pathogenesis and shed light on OUD treatment.

DeepFun: a deep learning sequence-based model to decipher non-coding variant effect in a tissue- and cell type-specific manner.

More than 90% of the genetic variants identified from genome-wide association studies (GWAS) are located in non-coding regions of the human genome. Here, we present a user-friendly web server, DeepFun (https://bioinfo.uth.