Comput Biol Chem. 2024 Nov 16;114:108251. doi: 10.1016/j.compbiolchem.2024.108251. Online ahead of print.

ABSTRACT

This paper demonstrates the utility of organized numerical representations of genes in research involving flat string gene formats (i.e., FASTA/FASTQ5). By assigning a unique vector embedding to each short sequence, it is possible to more efficiently cluster and improve upon compression performance for the string representations of cDNA libraries. Furthermore, by studying alternative coordinate vector embeddings trained on the context of codon triplets, we can demonstrate clustering based on amino acid properties. Employing this sequence embedding method to encode barcodes and cDNA sequences, we can improve the time complexity of similarity searches. By pairing vector embeddings with an algorithm that determines the vector proximity in Euclidean space, this approach enables quicker and more flexible sequence searches.

PMID:39602973 | DOI:10.1016/j.compbiolchem.2024.108251

Brief Bioinform. 2024 Nov 22;26(1):bbae623. doi: 10.1093/bib/bbae623.

ABSTRACT

Accumulating evidence indicates that long noncoding RNAs (lncRNAs) play important roles in molecular and cellular biology. Although many algorithms have been developed to reveal their associations with complex diseases by using downstream targets, the upstream (epi)genetic regulatory information has not been sufficiently leveraged to predict the function of lncRNAs in various biological processes. Therefore, we present FunlncModel, a machine learning-based interpretable computational framework, which aims to screen out functional lncRNAs by integrating a large number of (epi)genetic features and functional genomic features from their upstream/downstream multi-omic regulatory networks. We adopted the random forest method to mine nearly 60 features in three categories from >2000 datasets across 11 data types, including transcription factors (TFs), histone modifications, typical enhancers, super-enhancers, methylation sites, and mRNAs. FunlncModel outperformed alternative methods for classification performance in human embryonic stem cell (hESC) (0.95 Area Under Curve (AUROC) and 0.97 Area Under the Precision-Recall Curve (AUPRC)). It could not only infer the most known lncRNAs that influence the states of stem cells, but also discover novel high-confidence functional lncRNAs. We extensively validated FunlncModel's efficacy by up to 27 cancer-related functional prediction tasks, which involved multiple cancer cell growth processes and cancer hallmarks. Meanwhile, we have also found that (epi)genetic regulatory features, such as TFs and histone modifications, serve as strong predictors for revealing the function of lncRNAs. Overall, FunlncModel is a strong and stable prediction model for identifying functional lncRNAs in specific cellular contexts. FunlncModel is available as a web server at https://bio.liclab.net/FunlncModel/.

PMID:39602828 | DOI:10.1093/bib/bbae623

Sci Adv. 2024 Nov 29;10(48):eadp4670. doi: 10.1126/sciadv.adp4670. Epub 2024 Nov 27.

ABSTRACT

The introduction of immune checkpoint blockade (ICB) has markedly improved outcomes for advanced melanoma. However, many patients develop resistance through unknown mechanisms. While combination ICB has improved response rate and progression-free survival, it substantially increases toxicity. Biomarkers to distinguish patients who would benefit from combination therapy versus aPD-1 remain elusive. We analyzed whole-exome sequencing of pretreatment tumors from four cohorts (n = 140) of ICB-naïve patients treated with aPD-1. High genomic heterogeneity and low ploidy robustly identified patients intrinsically resistant to aPD-1. To establish clinically actionable predictions, we optimized and validated a predictive model using ploidy and heterogeneity to confidently identify (90% PPV) patients with intrinsic resistance to and worse survival on aPD-1. We further observed that three of seven (43%) patients predicted to be intrinsically resistant to single-agent PD-1 ICB responded to combination ICB, suggesting that these patients may benefit disproportionately from combination ICB. These findings highlight the importance of heterogeneity and ploidy, nominating an approach toward clinical actionability.

PMID:39602539 | DOI:10.1126/sciadv.adp4670

Plant J. 2024 Nov 27. doi: 10.1111/tpj.17164. Online ahead of print.

ABSTRACT

Cannabis sativa L., known for its medicinal and psychoactive properties, has recently experienced rapid market expansion but remains understudied in terms of its fundamental biology due to historical prohibitions. This pioneering study implements GS and ML to optimize cannabinoid profiles in cannabis breeding. We analyzed a representative population of drug-type cannabis accessions, quantifying major cannabinoids and utilizing high-density genotyping with 250K SNPs for GS. Our evaluations of various models-including ML algorithms, statistical methods, and Bayesian approaches-highlighted Random Forest's superior predictive accuracy for single and multi-trait genomic predictions, particularly for THC, CBD, and their precursors. Multi-trait analyses elucidated complex genetic interdependencies and identified key loci crucial to cannabinoid biosynthesis. These results demonstrate the efficacy of integrating GS and ML in developing cannabis varieties with tailored cannabinoid profiles.

PMID:39602132 | DOI:10.1111/tpj.17164

ACS Synth Biol. 2024 Nov 27. doi: 10.1021/acssynbio.4c00453. Online ahead of print.

ABSTRACT

Bacteria in the gastrointestinal tract play a crucial role in intestinal motility, homeostasis, and dysfunction. Unraveling the mechanisms by which microbes impact the host poses many challenges due to the extensive array of metabolites produced or metabolized by bacteria in the gut. Here, we describe the engineering of a gut commensal bacterium, Escherichia coli Nissle 1917, to biosynthesize the human metabolite serotonin for examining the effects of microbially produced biogenic amines on host physiology. Upon oral administration to mice, our engineered bacteria reach the large intestine, where they produce serotonin. Mice treated with serotonin-producing bacteria exhibited biological changes in the gut at transcriptional and physiological levels. This work establishes a novel framework employing engineered bacteria to modulate luminal serotonin levels and suggests potential clinical applications of modified microbial therapeutics to address gut disorders in humans.

PMID:39601776 | DOI:10.1021/acssynbio.4c00453

Biochem Soc Trans. 2024 Nov 27:BST20231240. doi: 10.1042/BST20231240. Online ahead of print.

ABSTRACT

Translational control is crucial for well-balanced cellular function and viability of organisms. Different mechanisms have evolved to up- and down-regulate protein synthesis, including 3' untranslated region (UTR)-mediated translation repression. RNA binding proteins or microRNAs interact with regulatory sequence elements located in the 3' UTR and interfere most often with the rate-limiting initiation step of translation. Dysregulation of post-transcriptional gene expression leads to various kinds of diseases, emphasizing the significance of understanding the mechanisms of these processes. So far, only limited mechanistic details about kinetics and dynamics of translation regulation are understood. This mini-review focuses on 3' UTR-mediated translational regulation mechanisms and demonstrates the potential of using single-molecule fluorescence-microscopy for kinetic and dynamic studies of translation regulation in vivo and in vitro.

PMID:39601754 | DOI:10.1042/BST20231240

Microbiol Resour Announc. 2024 Nov 27:e0105924. doi: 10.1128/mra.01059-24. Online ahead of print.

ABSTRACT

Streptomyces are Gram-positive bacteria typically found in the soil, with very large genomes and high GC content, and are known to produce a wide range of secondary metabolites. We isolated and sequenced the genomes of three Streptomyces bacteria from the soil of soybean field in Tsuruoka, Japan.

PMID:39601520 | DOI:10.1128/mra.01059-24

J Proteome Res. 2024 Nov 27. doi: 10.1021/acs.jproteome.4c00357. Online ahead of print.

ABSTRACT

Spontaneous Achilles tendon rupture (SATR) predominantly affects middle-aged and elderly individuals with chronic injuries. However, the exact cause and mechanism of SATR remain elusive, and potential therapeutic intervention or prevention is still insufficient. The present study aimed to uncover the key pathological molecules by using iTRAQ proteomics. The results identified 2432 candidate proteins in SATR patients using iTRAQ proteomic analysis. A total of 307 differentially expressed proteins (DEPs) were identified and linked to 211 KEGG signaling pathways including Coronavirus disease (COVID-19), focal adhesion, and ribosomes. GO enrichment analysis highlighted significant enrichment in processes such as biological adhesion, ossification, lipid (APOA4) processes, and extracellular matrix (ECM) organization (collagen). PPI network analysis identified hub genes such as serum albumin (ALB), fibronectin (FN1), and actin cytoplasmic 1. The WB analysis confirmed that FN1 and the receptor for activated C kinase (RACK1) were downregulated in the SATR tendon. Immunohistochemical staining revealed that collagen I and III were suppressed, while collagen II and APOA4 expression were higher in the SATR pathological tissue (P < 0.05). However, the primary cultured tenocytes (PCTs) from SATR patients showed enhanced proliferation and, consistent with tissue staining, reduced collagen I and III and increased collagen II. Our findings reveal vital targets and pathways in SATR's etiological progression, offering a new perspective on the diagnosis, treatment, and prognosis of this complex disorder.

PMID:39601082 | DOI:10.1021/acs.jproteome.4c00357

Bioinform Adv. 2024 Nov 13;4(1):vbae174. doi: 10.1093/bioadv/vbae174. eCollection 2024.

ABSTRACT

SUMMARY: We present py_cFBA, a Python-based toolbox for conditional flux balance analysis (cFBA). Our toolbox allows for an easy implementation of cFBA models using a well-documented and modular approach and supports the generation of Systems Biology Markup Language models. The toolbox is designed to be user-friendly, versatile, and freely available to non-commercial users, serving as a valuable resource for researchers predicting metabolic behaviour with resource allocation in dynamic-cyclic environments.

AVAILABILITY AND IMPLEMENTATION: Extensive documentation, installation steps, tutorials, and examples are available at https://tp-watson-python-cfba.readthedocs.io/en/. The py_cFBA python package is available at https://pypi.org/project/py-cfba/.

PMID:39600381 | PMC:PMC11593493 | DOI:10.1093/bioadv/vbae174

WIREs Mech Dis. 2024 Nov 26:e1654. doi: 10.1002/wsbm.1654. Online ahead of print.

ABSTRACT

Understanding of microbial pathogenesis has greatly revolutionized after conventional culture-based techniques are replaced by molecular methods. This technological shift is generating huge host-pathogen interactions (HPIs) data. Moreover, computational predictions of biological interactions are also adding to HPI understanding. Recently, several dedicated databases are developed for exclusively cataloging HPIs. Present article covers about some available HPI databases, types, and evolution of this area, along with recent trends in the application of these databases for biological research. As per the recent understanding in microbial pathogenesis, HPIs are considered highly dynamic in nature with multiple outcomes, which goes beyond simple microbes-disease association. Therefore, careful cataloging of complete information about HPIs can open several avenues to understand microbial pathogenesis considering their multifaceted effects on host system. HPI databases are indispensable tools for understanding microbial pathogenesis, and this article provides comprehensive information about their uses in the field of microbial pathogenesis research.

PMID:39600198 | DOI:10.1002/wsbm.1654

Viruses. 2024 Oct 31;16(11):1727. doi: 10.3390/v16111727.

ABSTRACT

Many vector-borne viruses are re-emerging as public health threats, yet our understanding of the virus-host interactions critical for productive infection remains limited. The ubiquitination of proteins, including host- and pathogen-derived proteins is a highly prominent and consistent post-translational modification that regulates protein function through signaling and degradation. Viral proteins are documented to hijack the host ubiquitination machinery to modulate multiple host processes including antiviral defense mechanisms. The engagement of the host ubiquitination machinery in the post-translational modification of viral proteins to support aspects of the viral life cycle including assembly and egress is also well documented. Exploring the role ubiquitination plays in the life cycle of vector-transmitted viral pathogens will increase the knowledge base pertinent to the impact of host-enabled ubiquitination of viral and host proteins and the consequences on viral pathogenesis. In this review, we explore E3 ligase-regulated ubiquitination pathways functioning as proviral and viral restriction factors in the context of acutely infectious, vector-transmitted viral pathogens and the potential for therapeutically targeting them for countermeasures development.

PMID:39599842 | DOI:10.3390/v16111727

Nutrients. 2024 Nov 19;16(22):3943. doi: 10.3390/nu16223943.

ABSTRACT

BACKGROUND: Endurance athletes require tailored nutrition strategies to optimize performance, recovery, and training adaptations. While traditional sports nutrition guidelines provide a foundational framework, individual variability in metabolic responses underscores the need for precision nutrition, informed by genetic, biological, and environmental factors. This scoping review evaluates the application of systems biology-driven sports nutrition for endurance athletes, focusing on 'omics' and wearable technologies.

METHODS: A scoping review of the literature was conducted in PubMed, Scopus, and Web of Science in accordance with the PRISMA-ScR checklist. Research questions, search strategies, and eligibility criteria were guided by the Population-Concept-Context framework with the following inclusion criteria: original research in English, involving endurance athletes, systems biology approaches, and nutritional interventions or continuous glucose monitoring (CGM).

RESULTS: Fifty-two studies were included, with distance runners as the most studied cohort. Eleven studies used metagenomics, eleven CGM, ten nutrigenetics, ten metabolomics, seven multi-omics, one proteomics, one epigenomics, and one lipidomics. Over half (n = 31; 60%) were randomized controlled trials (RCTs) with generally high methodological quality.

CONCLUSIONS: Most studies were proof-of-concept investigations aimed at assessing biomarkers; however, the evidence linking these biomarkers to performance, recovery, and long-term health outcomes in endurance athletes remains insufficient. Future research should focus on well-powered replicated crossover RCTs, multivariate N-of-1 clinical trials, 360-degree systems-wide approaches, and the validation of genetic impacts on nutritional interventions to refine dietary guidelines.

PMID:39599728 | DOI:10.3390/nu16223943

Nutrients. 2024 Nov 15;16(22):3897. doi: 10.3390/nu16223897.

ABSTRACT

BACKGROUND/OBJECTIVES: Sarcopenia involves the loss of muscle mass along with a decrease in muscle strength and physical performance. The aim of this paper was to compare the already published BIA equations for the estimation of Appendicular Skeletal Muscle Mass (ASMM) and Fat-Free Mass (FFM) with dual X-ray densitometer DXA estimations in order to determine whether Bioelectrical Impedance Analysis (BIA) could be a feasible application on a general population for the detection of low muscle mass and sarcopenia.

METHODS: Seventy-nine healthy women aged 40-70 years were included. Assessments involved BIA and DXA evaluations and anthropometric measurements.

RESULTS: DXA and BIA estimations showed great agreement, particularly the ones introduced by Scafoglieri et al. (2017) for ASMM (mean difference 1.81 kg) and Kanellakis et al. (2020) equation for FFM (mean difference 0.52 kg) resulted in the best fit for the cohort in analysis. BIA could intercept a low muscle mass condition which can be linked to sarcopenia.

CONCLUSIONS: This study showed how the use of BIA represents an effective and reliable method in the evaluation of sarcopenia.

PMID:39599682 | DOI:10.3390/nu16223897

Molecules. 2024 Nov 16;29(22):5406. doi: 10.3390/molecules29225406.

ABSTRACT

The philosophy of herbal medicines is that they contain multiple active components that target many aspects of a given disease. This is in line with the recent multiple-target strategy adopted due to shortcomings with the previous "magic bullet", single-target strategy. The complexity of biological systems means it is often difficult to elucidate the mechanisms of synergistic, additive, and/or multi-target (SAM) effects. However, the use of methodologies employing molecular docking offers some insight into these. The aim of this work was to review the uses of molecular-docking simulations in the detection and/or elucidation of SAM effects with herbal medicines. Molecular docking has revealed the potential for SAM effects with many different, individual herbal medicines. Docking can also improve the fundamental understanding of SAM effects as part of systems biology approaches, such as providing quantitative weightings for the connections within static networks or supplying estimates of kinetic parameters for dynamic metabolic networks. Molecular docking can also be combined with pharmacophore modeling in a hybrid method that greatly improves the efficiency of screening. Overall, molecular docking has been shown to be a highly useful tool to provide evidence for the efficacy of herbal medicines, previously only supported by traditional usage.

PMID:39598795 | DOI:10.3390/molecules29225406

Microorganisms. 2024 Nov 18;12(11):2348. doi: 10.3390/microorganisms12112348.

ABSTRACT

Archaeal group II chaperonins, also known as heat shock proteins (HSPs), are abundantly expressed in Sulfolobales. HSPα and HSPβ gene expression is upregulated during thermal shock. HSPs form large 18-mer complexes that assist in folding nascent proteins and protecting resident proteins during thermal stress. Engineered HSPs have been designed for industrial applications. Since temperature flux in the geothermal habitats of Sulfolobales impacts intracellular temperature, it follows that HSPs have developed thermotolerance. However, despite the low pH (i.e., pH < 4) typical for these habitats, intracellular pH in Sulfolobales is maintained at ~6.5. Therefore, it is not presumed that HSPs have evolved acid-tolerance. To test tolerance to low pH, HSPs were studied at various pH and temperature values. Both circular dichroism and intrinsic fluorescence indicate that HSPα and HSPβ retain structural integrity at neutral pH over a wide range of temperatures. Structural integrity is compromised for all HSPs at ultra-low pH (e.g., pH 2). Secondary structures in HSPs are resilient under mildly acidic conditions (pH 4) but Anilino naphthalene 8-sulfonate binding shows shifts in tertiary structure at lower pH. Trypsin digestion shows that the HSPβ-coh backbone is the most flexible and HSPβ is the most resilient. Overall, results suggest that HSPα and HSPβ exhibit greater thermostability than HSPβ-coh and that there are limits to HSP acid-tolerance. Molecular dynamics (MD) simulations complement the wet lab data. Specifically, MD suggests that the HSPβ secondary structure is the most stable. Also, despite similarities in pH- and temperature-dependent behavior, there are clear differences in how each HSP subtype is perturbed.

PMID:39597738 | DOI:10.3390/microorganisms12112348

Microorganisms. 2024 Oct 30;12(11):2187. doi: 10.3390/microorganisms12112187.

ABSTRACT

Well-annotated gene and genomic sequences serve as a foundation for making inferences in molecular biology and evolution and can directly impact public health. The first SARS-CoV-2 genome was submitted to the GenBank database hosted by the U.S. National Center for Biotechnology Information and used to develop the two successful vaccines. Conserved protein domains are often chosen as targets for developing antiviral medicines or vaccines. Mutation and substitution patterns provide crucial information not only on functional motifs and genome/protein interactions but also for characterizing phylogenetic relationships among viral strains. These patterns, together with the collection time of viral samples, serve as the basis for addressing the question of when and where the host-switching event occurred. Unfortunately, viral genomic sequences submitted to GenBank undergo little quality control, and critical information in the annotation is frequently changed without being recorded. Researchers often have no choice but to hold blind faith in the authenticity of the sequences. There have been reports of incorrect genome annotation but no report that casts doubt on the genomic sequences themselves because it seems theoretically impossible to identify genomic sequences that may not be authentic. This paper takes an innovative approach to show that some SARS-CoV-2 genomes submitted to GenBank cannot possibly be authentic. Specifically, some SARS-CoV-2 genomic sequences deposited in GenBank with collection times in 2023 and 2024, isolated from saliva, nasopharyngeal, sewage, and stool, are identical to the reference genome of SARS-CoV-2 (NC_045512). The probability of such occurrence is effectively 0. I also compile SARS-CoV-2 genomes with changed sample collection times. One may be led astray in bioinformatic analysis without being aware of errors in sequences and sequence annotation.

PMID:39597576 | DOI:10.3390/microorganisms12112187

Biology (Basel). 2024 Nov 16;13(11):936. doi: 10.3390/biology13110936.

ABSTRACT

Myo-inositol (MYO) and D-chiro-inositol (DCI) are the two most significant isomeric forms of inositol, playing a critical role in intracellular signaling. MYO is the most abundant form of inositol in nature; DCI is produced from MYO through epimerization by an insulin-dependent enzyme. Recently, it has been demonstrated that inositol may influence oocyte maturation and improve intracellular Ca2+ oscillation in the oocytes, and it has been proposed as a potential intervention for restoring spontaneous ovulation. The MYO concentration in human follicular fluid is considered a bioindicator of oocyte quality. In the ovary, DCI modulates the activity of aromatase, thus regulating androgen synthesis. Under physiological conditions, the MYO/DCI ratio is maintained at 40:1 in plasma. In women with PCOS, the MYO/DCI ratio is lowered to 0:2:1, contributing to elevated androgen production. By regulating FSH signaling, MYO administration increases the number of high-quality embryos available for transfer in poor responder patients. Finally, by acting downstream to insulin signaling, inositol administration during pregnancy may represent a novel strategy for counteracting gestational diabetes. These findings show that diet supplementation with inositol may be a promising strategy to address female infertility and sustain a healthy pregnancy.

PMID:39596891 | DOI:10.3390/biology13110936

Biology (Basel). 2024 Nov 14;13(11):925. doi: 10.3390/biology13110925.

ABSTRACT

Agricultural and industrial activities are increasing pollution of water bodies with low doses of xenobiotics that have detrimental effects on aquaculture. The aim of this work was to determine the possibility of using Levilactobacillus brevis 47f culture in fish aquaculture under the influence of low doses of xenobiotics as an adaptogen. An increase in the survival of Danio rerio individuals exposed to the xenobiotic bisphenol A solution and fed with the L. brevis 47f was shown compared to control groups and, at the same time, the cytokine profile in the intestinal tissues of Danio rerio was also investigated. Analysis of differential gene expression of the L. brevis 47f grown under the action of high concentrations of bisphenol A showed changes in mRNA levels of a number of genes, including genes of various transport proteins, genes involved in fatty acid synthesis, genes of transcriptional regulators, genes of the arabinose operon, and the oppA gene. The identification of L. brevis 47f proteins from polyacrylamide gel by mass spectrometry revealed L-arabinose isomerase, Clp chaperone subunit, ATP synthase subunits, pentose phosphate pathway and glycolysis enzyme proteins, which are likely part of the L. brevis 47f strain's anti-stress response, but probably do not affect its adaptogenic activity toward Danio rerio.

PMID:39596880 | DOI:10.3390/biology13110925

Biology (Basel). 2024 Oct 30;13(11):884. doi: 10.3390/biology13110884.

ABSTRACT

Translation is a fundamental process in biology, and understanding its mechanisms is crucial to comprehending cellular functions and diseases. The regulation of this process is closely linked to the structure of mRNA, as these regions prove vital to modulating translation efficiency and control. Thus, identifying and investigating these fundamental factors that influence the processing and unwinding of structured mRNAs would be of interest due to the widespread impact in various fields of biology. To this end, we employed a computational approach and identified genes that may be involved in the translation of structured mRNAs. The approach is based on the enrichment of interactions and co-expression of genes with those that are known to influence translation and helicase activity. The in silico prediction found CAF20 and ECM32 to be highly ranked candidates that may play a role in unwinding mRNA. The activities of neither CAF20 nor ECM32 have previously been linked to the translation of PGM2 mRNA or other structured mRNAs. Our follow-up investigations with these two genes provided evidence of their participation in the translation of PGM2 mRNA and several other synthetic structured mRNAs.

PMID:39596839 | DOI:10.3390/biology13110884

Genes (Basel). 2024 Nov 12;15(11):1456. doi: 10.3390/genes15111456.

ABSTRACT

BACKGROUND: Phanera Lour., a genus in the subfamily Cercidoideae of the family Leguminosae, is characterized by woody liana habit, tendrils, and distinctive bilobate or bifoliolate leaves. The genus holds important medicinal value and constitutes a complex group characterized by morphological diversity and unstable taxonomic boundaries. However, limited information on the chloroplast genomes of this genus currently available constrains our understanding of its species diversity. Hence, it is necessary to obtain more chloroplast genome information to uncover the genetic characteristics of this genus.

METHODS: We collected and assembled the complete chloroplast genomes of nine representative Phanera plants, including Phanera erythropoda, Phanera vahlii, Phanera aureifolia, Phanera bidentata, Phanera japonica, Phanera saigonensis, Phanera championii, Phanera yunnanensis, and Phanera apertilobata. We then conducted a comparative analysis of these genomes and constructed phylogenetic trees.

RESULTS: These species are each characterized by a typical quadripartite structure. A total of 130-135 genes were annotated, and the GC content ranged from 39.25-42.58%. Codon usage analysis indicated that codons encoding alanine were dominant. We found 82-126 simple sequence repeats, along with 5448 dispersed repeats, mostly in the form of forward repeats. Phylogenetic analysis revealed that 16 Phanera species form a well-supported monophyletic group, suggesting a possible monophyletic genus. Furthermore, 10 hypervariable regions were detected for identification and evolutionary studies.

CONCLUSIONS: We focused on comparing chloroplast genome characteristics among nine Phanera species and conducted phylogenetic analyses, laying the foundation for further phylogenetic research and species identification of Phanera.

PMID:39596656 | DOI:10.3390/genes15111456