genome research

MOTIVATION: Accurate inference of potential Drug-protein interactions (DPIs) aids in understanding drug mechanisms and developing novel treatments. Existing deep learning models, however, struggle with accurate node representation in DPI prediction, limiting their performance. RESULTS: We propose a new computational framework that integrates global and local features of nodes in the drug-protein bipartite graph for efficient DPI inference. Initially, we employ pre-trained models to acquire fundamental knowledge of drugs and proteins and to determine their initial features...

Simple sequence repeats (SSRs) are found in nonrandom distributions in genomes and are thought to impact gene expression. The distribution patterns of 48 295 SSRs of Paphiopedilum malipoense are mined and characterized based on the first full-length transcriptome and comprehensive transcriptome dataset from 12 organs. Statistical genomics analyses are used to investigate how SSRs in transcripts affect gene expression. The results demonstrate the correlations between SSR distributions, characteristics, and expression level...

The CRISPR-Cas9 technology has the potential to revolutionize the treatment of various diseases, including Rett syndrome, by enabling the correction of genes or mutations in human patient cells. However, several challenges need to be addressed before its widespread clinical application. These challenges include the low delivery efficiencies to target cells, the actual efficiency of the genome-editing process, and the precision with which the CRISPR-Cas system operates. Herein, the study presents a Magnetic Nanoparticle-Assisted Genome Editing (MAGE) platform, which significantly improves the transfection efficiency, biocompatibility, and genome-editing accuracy of CRISPR-Cas9 technology...

The Y chromosome has recognized functions in promoting male sex determination and regulating aspects of fertility. However, recent work has demonstrated important roles for the Y chromosome and Y-encoded genes in multiple domains of male health, including cancer. It is well-established that males experience shorter life spans than females, and this sex bias on overall mortality is ac-centuated in populations with longer life expectancy, in part related to elevated rates of cancer. The majority of human malignancies exhibit a sex bias with elevated frequencies in males...

The relationship between fine particulate matter (PM2.5) and blood pressure (BP) is a controversial issue. We conducted a two-sample Mendelian randomization (MR) analysis and identified 58 genome-wide significant single-nucleotide polymorphisms associated with PM2.5 as instrument variables. Inverse-variance weighted (IVW) was used as the primary analysis approach. MR-Egger, weighted median, simple model, and weighted model methods were selected for quality control. We found a significant negative causal association of higher genetically predicted PM2...

As the contribution of de novo mutations (DNMs) to human genetic diseases has been gradually uncovered, analyzing the global research landscape over the past 20 years is essential. Because of the large and rapidly increasing number of publications in this field, understanding the current landscape of the contribution of DNMs in the human genome to genetic diseases remains a challenge. Bibliometric analysis provides an approach for visualizing these studies using information in published records in a specific field...

Transcription factor RBPJ is the central component in Notch signal transduction and directly forms a coactivator complex together with the Notch intracellular domain (NICD). While RBPJ protein levels remain constant in most tissues, dynamic expression of Notch target genes varies depending on the given cell-type and the Notch activity state. To elucidate dynamic RBPJ binding genome-wide, we investigated RBPJ occupancy by ChIP-Seq. Surprisingly, only a small set of the total RBPJ sites show a dynamic binding behavior in response to Notch signaling...

L1 elements are retrotransposons currently active in mammals. Although L1s are typically silenced in most normal tissues, elevated L1 expression is associated with a variety of conditions, including cancer, aging, infertility and neurological disease. These associations have raised interest in the mapping of human endogenous de novo L1 insertions, and a variety of methods have been developed for this purpose. Adapting these methods to mouse genomes would allow us to monitor endogenous in vivo L1 activity in controlled, experimental conditions using mouse disease models...

Structured noncoding RNAs (ncRNAs) contribute to many important cellular processes involving chemical catalysis, molecular recognition and gene regulation. Few ncRNA classes are broadly distributed among organisms from all three domains of life, but the list of rarer classes that exhibit surprisingly diverse functions is growing. We previously developed a computational pipeline that enables the near-comprehensive identification of structured ncRNAs expressed from individual bacterial genomes. The regions between protein coding genes are first sorted based on length and the fraction of guanosine and cytidine nucleotides...

Chromatin architecture regulates gene expression and shapes cellular identity, particularly in neuronal cells. Specifically, polycomb group (PcG) proteins enable establishment and maintenance of neuronal cell type by reorganizing chromatin into repressive domains that limit the expression of fate-determining genes and sustain distinct gene expression patterns in neurons. Here, we map the 3D genome architecture in neuronal and non-neuronal cells isolated from the Wernicke's area of four human brains and comprehensively analyze neuron-specific aspects of chromatin organization...

CpG islands near promoters are normally unmethylated despite being surrounded by densely methylated regions. Aberrant hypermethylation of these CpG islands has been associated with the development of various human diseases. Although local genetic elements have been speculated to play a role in protecting promoters from methylation, only a limited number of methylation barriers have been identified. In this study, we conducted an integrated computational and experimental investigation of colorectal cancer methylomes...

CRISPR-Cas systems have widely been adopted as genome editing tools, with two frequently employed Cas nucleases being SpyCas9 and LbCas12a. Although both nucleases use RNA guides to find and cleave target DNA sites, the two enzymes differ in terms of protospacer-adjacent motif (PAM) requirements, guide architecture and cleavage mechanism. In the last years, rational engineering led to the creation of PAM-relaxed variants SpRYCas9 and impLbCas12a to broaden the targetable DNA space. By employing their catalytically inactive variants (dCas9/dCas12a), we quantified how the protein-specific characteristics impact the target search process...

The possible effects of mutations on stability and function of a protein can only be understood in the context of protein 3D structure. The MutationExplorer webserver maps sequence changes onto protein structures and allows users to study variation by inputting sequence changes. As the user enters variants, the 3D model evolves, and estimated changes in energy are highlighted. In addition to a basic per-residue input format, MutationExplorer can also upload an entire replacement sequence. Previously the purview of desktop applications, such an upload can back-mutate PDB structures to wildtype sequence in a single step...

BACKGROUND: Atopic dermatitis ranks among the prevalent skin disorders. Research has indicated a potential association with brain cancer. Yet, establishing a direct causal relationship between atopic dermatitis and brain cancer continues to be challenging. MATERIALS AND METHODS: We extracted single nucleotide polymorphisms (SNPs) significantly associated with atopic dermatitis (sample size = 382 254) at a genome-wide level from a large Finnish Genome-Wide Association Study (GWAS) dataset (n cases = 15 208, n controls = 367 046)...

Crop health directly affects yields and food security. At present, agrochemicals such as fertilizers and pesticides are mainly used in agricultural production to promote crop health. However, long-term excessive utilization of agrochemicals will damage the ecological environment of farmlands and increase the safety risk of agricultural products. It is urgent to explore efficient and environment-friendly agricultural products. Rhizosphere microbiome are considered as the second genome of plants, which are closely related to crop health...

Preparation of DNA polymorphism datasets for analysis is an important step in evolutionary genetic and molecular ecology studies. Ever-growing dataset sizes make this step time consuming, but few convenient software tools are available to facilitate processing of large-scale datasets including thousands of sequence alignments. Here I report "processor of sequences v4" (proSeq4)-a user-friendly multiplatform software for preparation and evolutionary genetic analyses of genome- or transcriptome-scale sequence polymorphism datasets...

BACKGROUND: In August 2023, the BA.2.86 SARS-CoV-2 variant, with over 30 spike protein mutations, emerged amidst the global dominance of XBB sub-lineages. It evolved into JN.1 by late 2023, spreading across 71 countries. JN.1, distinct for its L455S mutation, significantly dominated global sequences, raising concerns over its transmission and clinical impact. The study investigates JN.1's clinical severity and its effect on hospital admissions in Maharashtra, India. METHODOLOGY: The present study involved 3,150 curated Indian SARS-CoV-2 whole genome sequences with collection dates between 1st August 2023 and 15th January 2024...

Given that colorectal cancer is one of the leading causes of mortality, mucinous adenocarcinoma is one of the subtypes and is characterized by the presence of mucin-producing tumor cells with mucin components and is more challenging to manage. In Saudi Arabia, it represents approximately 10-15% of all colorectal carcinoma. The main etiological cause of mucinous adenocarcinoma is yet not well understood. The main goal of our study is to discuss the histopathology and the molecular background of mucinous colorectal adenocarcinoma and also to provide an update on its prognosis and therapeutics from recent published literature...

This opinion piece emphasies the critical role of translational research in enhancing the UK's resilience against future pandemics. The COVID-19 pandemic demonstrated the lifesaving potential of scientific innovation, including genomic tracking of SARS-CoV-2, vaccine development, data linkage, modelling, and new treatments. These advances, achieved through collaborations between academic institutions, industry, government, public health bodies, and the NHS, occurred at an unprecedented pace. However, the UK's pandemic preparedness planning, as reflected in the 2016 Exercise Cygnus report, notably lacked provision for scientific innovation...

By modifying immune cells, immunotherapy can activate immune response to establish long-term immune memory and prevent tumor recurrence. However, their effectiveness is largely constricted by the poor immunogenicity, immune escape, and immune tolerance of the tumor. This is related to the characteristics of the tumor itself, such as genome instability and mutation. The combination of various nanocarriers with tumor immunotherapy is beneficial for overcoming the shortcomings of traditional immunotherapy. Nanocarriers coated by cell membranes can extend blood circulation time, improve ability to evade immune clearance, and enhance targeting, thus significantly enhancing the efficacy of immunotherapy and showing great potential in tumor immunotherapy...