Nature. 2023 May 10. doi: 10.1038/s41586-023-06053-0. Online ahead of print.

ABSTRACT

Different plant species within the grasses were parallel targets of domestication, giving rise to crops with distinct evolutionary histories and traits1. Key traits that distinguish these species are mediated by specialized cell types2. Here we compare the transcriptomes of root cells in three grass species-Zea mays, Sorghum bicolor and Setaria viridis. We show that single-cell and single-nucleus RNA sequencing provide complementary readouts of cell identity in dicots and monocots, warranting a combined analysis. Cell types were mapped across species to identify robust, orthologous marker genes. The comparative cellular analysis shows that the transcriptomes of some cell types diverged more rapidly than those of others-driven, in part, by recruitment of gene modules from other cell types. The data also show that a recent whole-genome duplication provides a rich source of new, highly localized gene expression domains that favour fast-evolving cell types. Together, the cell-by-cell comparative analysis shows how fine-scale cellular profiling can extract conserved modules from a pan transcriptome and provide insight on the evolution of cells that mediate key functions in crops.

PMID:37165193 | DOI:10.1038/s41586-023-06053-0

Cell Res. 2023 May 10. doi: 10.1038/s41422-023-00819-x. Online ahead of print.

NO ABSTRACT

PMID:37165065 | DOI:10.1038/s41422-023-00819-x

Nat Commun. 2023 May 10;14(1):2687. doi: 10.1038/s41467-023-38183-4.

ABSTRACT

Availability of light and CO2, substrates of microalgae photosynthesis, is frequently far from optimal. Microalgae activate photoprotection under strong light, to prevent oxidative damage, and the CO2 Concentrating Mechanism (CCM) under low CO2, to raise intracellular CO2 levels. The two processes are interconnected; yet, the underlying transcriptional regulators remain largely unknown. Employing a large transcriptomic data compendium of Chlamydomonas reinhardtii's responses to different light and carbon supply, we reconstruct a consensus genome-scale gene regulatory network from complementary inference approaches and use it to elucidate transcriptional regulators of photoprotection. We show that the CCM regulator LCR1 also controls photoprotection, and that QER7, a Squamosa Binding Protein, suppresses photoprotection- and CCM-gene expression under the control of the blue light photoreceptor Phototropin. By demonstrating the existence of regulatory hubs that channel light- and CO2-mediated signals into a common response, our study provides an accessible resource to dissect gene expression regulation in this microalga.

PMID:37164999 | DOI:10.1038/s41467-023-38183-4

Am J Respir Crit Care Med. 2023 May 10. doi: 10.1164/rccm.202211-2107OC. Online ahead of print.

ABSTRACT

RATIONALE: Children with preschool wheezing or school-age asthma are reported to have airway microbial imbalances.

OBJECTIVE: To identify clusters in children with asthma or wheezing using oropharyngeal microbiota profiles.

METHODS: Oropharyngeal swabs, from the Unbiased BIOmarkers for the Prediction of REspiratory Disease outcomes pediatric asthma/wheezing cohort, were characterized by 16S rRNA gene sequencing and unsupervised hierarchical clustering was performed on the Bray-Curtis β-diversity. Enrichment scores (ESs) of the MSigDB Hallmark gene sets were computed from the blood transcriptome using gene set variation analysis. Children with severe asthma or severe wheezing were followed up for 12-18 months, with assessing the frequency of exacerbations.

MEASUREMENTS AND MAIN RESULTS: Oropharyngeal samples of 241 children (age range: 1-17 years, 40% female) revealed 4 taxa-driven clusters dominated by Streptococcus, Veillonella, Rothia and Haemophilus, respectively. The clusters showed significant differences in atopic dermatitis, grass pollen sensitization, FEV1 % predicted post-salbutamol, and the annual asthma exacerbation frequency during follow-up. The Veillonella-cluster was the most allergic and included highest percentage of children with ≥2 exacerbations/year during follow-up. The oropharyngeal clusters were different in the ESs of transforming growth factor β (highest in Veillonella-cluster) and Wnt/β-Catenin signaling (highest in Haemophilus-cluster) transcriptomic pathways in blood (all q-values < 0.05).

CONCLUSION: The analysis of the oropharyngeal microbiota of children with asthma/wheezing identified four clusters with distinct clinical characteristics (phenotypes) that associate with exacerbations' risk and transcriptomic pathways involved in airway remodeling. This suggests that further exploration of the oropharyngeal microbiota may lead to novel pathophysiological insights and potentially new treatment approaches.

PMID:37163754 | DOI:10.1164/rccm.202211-2107OC

PLoS One. 2023 May 10;18(5):e0274065. doi: 10.1371/journal.pone.0274065. eCollection 2023.

ABSTRACT

Downstream analysis of virus-infected cell samples, such as reverse transcription polymerase chain reaction (RT PCR) or mass spectrometry, often needs to be performed at lower biosafety levels than their actual cultivation, and thus the samples require inactivation before they can be transferred. Common inactivation methods involve chemical crosslinking with formaldehyde or denaturing samples with strong detergents, such as sodium dodecyl sulfate. However, these protocols destroy the protein quaternary structure and prevent the analysis of protein complexes, albeit through different chemical mechanisms. This often leads to studies being performed in over-expression or surrogate model systems. To address this problem, we generated a protocol that achieves the inactivation of infected cells through ultraviolet (UV) irradiation. UV irradiation damages viral genomes and crosslinks nucleic acids to proteins but leaves the overall structure of protein complexes mostly intact. Protein analysis can then be performed from intact cells without biosafety containment. While UV treatment protocols have been established to inactivate viral solutions, a protocol was missing to inactivate crude infected cell lysates, which heavily absorb light. In this work, we develop and validate a UV inactivation protocol for SARS-CoV-2, HSV-1, and HCMV-infected cells. A fluence of 10,000 mJ/cm2 with intermittent mixing was sufficient to completely inactivate infected cells, as demonstrated by the absence of viral replication even after three sequential passages of cells inoculated with the treated material. The herein described protocol should serve as a reference for inactivating cells infected with these or similar viruses and allow for the analysis of protein quaternary structure from bona fide infected cells.

PMID:37163509 | DOI:10.1371/journal.pone.0274065

mBio. 2023 May 10:e0024023. doi: 10.1128/mbio.00240-23. Online ahead of print.

ABSTRACT

Mitoviruses in the family Mitoviridae are the mitochondria-replicating "naked RNA viruses" with genomes encoding only the replicase RNA-dependent RNA polymerase (RdRp) and prevalent across fungi, plants, and invertebrates. Arbuscular mycorrhizal fungi in the subphylum Glomeromycotina are obligate plant symbionts that deliver water and nutrients to the host. We discovered distinct mitoviruses in glomeromycotinian fungi, namely "large duamitovirus," encoding unusually large RdRp with a unique N-terminal motif that is endogenized in some host genomes. More than 400 viral sequences similar to the large duamitoviruses are present in metatranscriptome databases. They are globally distributed in soil ecosystems, consistent with the cosmopolitan distribution of glomeromycotinian fungi, and formed the most basal clade of the Mitoviridae in phylogenetic analysis. Given that glomeromycotinian fungi are the only confirmed hosts of these viruses, we propose the hypothesis that large duamitoviruses are the most ancestral lineage of the Mitoviridae that have been maintained exclusively in glomeromycotinian fungi.

PMID:37162347 | DOI:10.1128/mbio.00240-23

Prep Biochem Biotechnol. 2023 May 10:1-9. doi: 10.1080/10826068.2023.2207204. Online ahead of print.

ABSTRACT

In this study, an engineered strain of Saccharomyces cerevisiae was used to produce taxadiene, a precursor in the biosynthetic pathway of the anticancer drug paclitaxel. Taxadiene was recovered in situ with the polymeric adsorbent Diaion © HP-20. Here we tested two bioreactor configurations and adsorbent concentrations to maximize the production and recovery of taxadiene. An external recovery configuration (ERC) was performed with the integration of an expanded bed adsorption column, whereas the internal recovery configuration (IRC) consisted in dispersed beads inside the bioreactor vessel. Taxadiene titers recovered in IRC were higher to ERC by 3.4 and 3.5 fold by using 3% and 12% (w/v) adsorbent concentration respectively. On the other hand, cell growth kinetics were faster in ERC which represents an advantage in productivity (mg of taxadiene/L*h). High resin bead concentration (12% w/v) improved the partition of taxadiene onto the beads up to 98%. This result represents an advantage over previous studies using a 3% resin concentration where the partition of taxadiene on the beads was around 50%. This work highlights the potential of in situ product recovery to improve product partition, reduce processing steps and promote cell growth. Nevertheless, a careful design of bioreactor configuration and process conditions is critical.

PMID:37162336 | DOI:10.1080/10826068.2023.2207204

Syst Biol. 2023 May 10:syad021. doi: 10.1093/sysbio/syad021. Online ahead of print.

ABSTRACT

Higher-level classifications often must account for monotypic taxa representing depauperate evolutionary lineages and lacking synapomorphies of their better-known, well-defined sister clades. In a ranked (Linnean) or unranked (phylogenetic) classification system, discovering such a depauperate taxon does not necessarily invalidate the rank classification of sister clades. Named higher taxa must be monophyletic to be phylogenetically valid. Ranked taxa above the species level should also maximize information content, diagnosability, and utility (e.g., in biodiversity conservation). In spider classification, families are the highest rank that is systematically catalogued, and incertae sedis is not allowed. Consequently, it is important that family level taxa be well defined and informative. We revisit the classification problem of Orbipurae, an unranked suprafamilial clade containing the spider families Nephilidae, Phonognathidae, and Araneidae sensu stricto. We argue that, to maximize diagnosability, information content, conservation utility, and practical taxonomic considerations, this "splitting" scheme is superior to its recently proposed alternative, which lumps these families together as Araneidae sensu lato. We propose to redefine Araneidae and recognize a monogeneric spider family, Paraplectanoididae fam. nov. to accommodate the depauperate lineage Paraplectanoides. We present new subgenomic data to stabilize Orbipurae topology which also supports our proposed family-level classification. Our example from spiders demonstrates why classifications must be able to accommodate depauperate evolutionary lineages, e.g., Paraplectanoides. Finally, although clade age should not be a criterion to determine rank, other things being equal, comparable ages of similarly ranked taxa do benefit comparative biology.

PMID:37161751 | DOI:10.1093/sysbio/syad021

Genome Biol. 2023 May 9;24(1):110. doi: 10.1186/s13059-023-02948-3.

ABSTRACT

Understanding coding mutations is important for many applications in biology and medicine but the vast mutation space makes comprehensive experimental characterisation impossible. Current predictors are often computationally intensive and difficult to scale, including recent deep learning models. We introduce Sequence UNET, a highly scalable deep learning architecture that classifies and predicts variant frequency from sequence alone using multi-scale representations from a fully convolutional compression/expansion architecture. It achieves comparable pathogenicity prediction to recent methods. We demonstrate scalability by analysing 8.3B variants in 904,134 proteins detected through large-scale proteomics. Sequence UNET runs on modest hardware with a simple Python package.

PMID:37161576 | DOI:10.1186/s13059-023-02948-3

Math Biosci Eng. 2023 Mar 21;20(5):9572-9606. doi: 10.3934/mbe.2023420.

ABSTRACT

Complete spontaneous tumor regression (without treatment) is well documented to occur in animals and humans as epidemiological analysis show, whereby the malignancy is permanently eliminated. We have developed a novel computational systems biology model for this unique phenomenon to furnish insight into the possibility of therapeutically replicating such regression processes on tumors clinically, without toxic side effects. We have formulated oncological informatics approach using cell-kinetics coupled differential equations while protecting normal tissue. We investigated three main tumor-lysis components: (ⅰ) DNA blockade factors, (ⅱ) Interleukin-2 (IL-2), and (ⅲ) Cytotoxic T-cells (CD8+ T). We studied the temporal variations of these factors, utilizing preclinical experimental investigations on malignant tumors, using mammalian melanoma microarray and histiocytoma immunochemical assessment. We found that permanent tumor regression can occur by: 1) Negative-Bias shift in population trajectory of tumor cells, eradicating them under first-order asymptotic kinetics, and 2) Temporal alteration in the three antitumor components (DNA replication-blockade, Antitumor T-lymphocyte, IL-2), which are respectively characterized by the following patterns: (a) Unimodal Inverted-U function, (b) Bimodal M-function, (c) Stationary-step function. These provide a time-wise orchestrated tri-phasic cytotoxic profile. We have also elucidated gene-expression levels corresponding to the above three components: (ⅰ) DNA-damage G2/M checkpoint regulation [genes: CDC2-CHEK], (ⅱ) Chemokine signaling: IL-2/15 [genes: IL2RG-IKT3], (ⅲ) T-lymphocyte signaling (genes: TRGV5-CD28). All three components quantitatively followed the same activation profiles predicted by our computational model (Smirnov-Kolmogorov statistical test satisfied, α = 5%). We have shown that the genes CASP7-GZMB are signatures of Negative-bias dynamics, enabling eradication of the residual tumor. Using the negative-biasing principle, we have furnished the dose-time profile of equivalent therapeutic agents (DNA-alkylator, IL-2, T-cell input) so that melanoma tumor may therapeutically undergo permanent extinction by replicating the spontaneous tumor regression dynamics.

PMID:37161256 | DOI:10.3934/mbe.2023420

Nat Commun. 2023 May 9;14(1):2463. doi: 10.1038/s41467-023-37863-5.

ABSTRACT

Chimeric antigen receptors (CARs) and synthetic Notch (synNotch) receptors are engineered cell-surface receptors that sense a target antigen and respond by activating T cell receptor signaling or a customized gene program, respectively. Here, to expand the targeting capabilities of these receptors, we develop "universal" receptor systems for which receptor specificity can be directed post-translationally via covalent attachment of a co-administered antibody bearing a benzylguanine (BG) motif. A SNAPtag self-labeling enzyme is genetically fused to the receptor and reacts with BG-conjugated antibodies for covalent assembly, programming antigen recognition. We demonstrate that activation of SNAP-CAR and SNAP-synNotch receptors can be successfully targeted by clinically relevant BG-conjugated antibodies, including anti-tumor activity of SNAP-CAR T cells in vivo in a human tumor xenograft mouse model. Finally, we develop a mathematical model to better define the parameters affecting universal receptor signaling. SNAP receptors provide a powerful strategy to post-translationally reprogram the targeting specificity of engineered cells.

PMID:37160880 | DOI:10.1038/s41467-023-37863-5

Eur Biophys J. 2023 May 9. doi: 10.1007/s00249-023-01652-1. Online ahead of print.

ABSTRACT

The biotech industry has great interest in investigating therapeutic proteins in high concentration environments like human serum. The fluorescence detection system (Aviv-FDS) allows the performance of analytical ultracentrifuge (AUC) sedimentation velocity (SV) experiments in tracer or BOLTS protocols. Here, we compare six pooled human serum samples by AUC SV techniques and demonstrate the potential of this technology for characterizing therapeutic antibodies in serum. Control FDS SV experiments on serum alone reveal a bilirubin-HSA complex whose sedimentation is slowed by solution nonideality and exhibits a Johnston-Ogston (JO) effect due to the presence of high concentrations of IgG. Absorbance SV experiments on diluted serum samples verify the HSA-IgG composition as well as a significant IgM pentamer boundary at 19 s. Alexa-488 labeled Simponi (Golimumab) is used as a tracer to investigate the behavior of a therapeutic monoclonal antibody (mAb) in serum, and the sedimentation behavior of total IgG in serum. Serum dilution experiments allow extrapolation to zero concentration to extract so, while global direct boundary fitting with SEDANAL verifies the utility of a matrix of self- and cross-term phenomenological nonideality coefficients (ks and BM1) and the source of the JO effect. The best fits include weak reversible association (~ 4 × 103 M-1) between Simponi and total human IgG. Secondary mAbs to human IgG and IgM verify the formation of a 10.2 s 1:1 complex with human IgG and a 19 s complex with human IgM pentamers. These results demonstrate that FDS AUC allows a range of approaches for investigating therapeutic antibodies in human serum.

PMID:37160443 | DOI:10.1007/s00249-023-01652-1

Immunity. 2023 May 2:S1074-7613(23)00177-2. doi: 10.1016/j.immuni.2023.04.013. Online ahead of print.

ABSTRACT

Glial cells and central nervous system (CNS)-infiltrating leukocytes contribute to multiple sclerosis (MS). However, the networks that govern crosstalk among these ontologically distinct populations remain unclear. Here, we show that, in mice and humans, CNS-resident astrocytes and infiltrating CD44hiCD4+ T cells generated interleukin-3 (IL-3), while microglia and recruited myeloid cells expressed interleukin-3 receptor-ɑ (IL-3Rɑ). Astrocytic and T cell IL-3 elicited an immune migratory and chemotactic program by IL-3Rɑ+ myeloid cells that enhanced CNS immune cell infiltration, exacerbating MS and its preclinical model. Multiregional snRNA-seq of human CNS tissue revealed the appearance of IL3RA-expressing myeloid cells with chemotactic programming in MS plaques. IL3RA expression by plaque myeloid cells and IL-3 amount in the cerebrospinal fluid predicted myeloid and T cell abundance in the CNS and correlated with MS severity. Our findings establish IL-3:IL-3RA as a glial-peripheral immune network that prompts immune cell recruitment to the CNS and worsens MS.

PMID:37160117 | DOI:10.1016/j.immuni.2023.04.013

Med J Islam Repub Iran. 2022 Dec 24;36:170. doi: 10.47176/mjiri.36.170. eCollection 2022.

ABSTRACT

BACKGROUND: Lower respiratory tract infections, chronic obstructive pulmonary disease (COPD), tuberculosis, and lung cancer are among the leading 10 causes of death worldwide. The Board of Respiratory Diseases Research Network (RDRN), a sub-committee of the Iranian Non-Communicable Diseases Committee (INCDC) is particularly concerned that there should be a coordinated National strategy to address the burden caused by chronic respiratory diseases.

METHODS: Iranian Ministry of Health and Medical Education (MoHME) has decided to give promotion to the establishment of research networks and use them as the milestones for research management, particularly for the national health priorities.

RESULTS: National Service Framework (NSF), which was designed for Chronic Respiratory Diseases, is one of the main outcomes of the chronic respiratory diseases sub-committee of INCDC. The main seven strategies were represented by the Steering Committee in 2010 for a period of 10 years. Successful development and implementation of our goals provide the CRDs sub-committee of INCDC with the opportunity to develop a paradigm to prevent chronic respiratory diseases.

CONCLUSION: A stronger national plan for controlling chronic respiratory diseases will ensure stronger advocacy to support respiratory health at national, sub-national, and regional levels.

PMID:37159756 | PMC:PMC10163208 | DOI:10.47176/mjiri.36.170

J Clin Endocrinol Metab. 2023 May 9:dgad258. doi: 10.1210/clinem/dgad258. Online ahead of print.

ABSTRACT

CONTEXT: Sleep disruption is associated with poorer glucose metabolic control and altered gut microbiota in animal models.

OBJECTIVE: We aimed to evaluate the possible links among REM sleep duration, continuous glucose levels and gut microbiota composition.

DESIGN: This is an observational, prospective, real-life, cross-sectional case-control study.

SETTING: Tertiary Hospital recruiting healthy volunteers.

PATIENTS OR OTHER PARTICIPANTS: One-hundred and eighteen (60 with obesity), middle-aged (39.1-54.8) subjects.

INTERVENTION(S): Glucose variability and REM sleep duration were assessed by 10-day continuous glucose monitoring (CGM) (Dexcom G6®) and wrist-actigraphy (Fitbit Charge 3®), respectively.

MAIN OUTCOME MEASURE(S): . Glucose variability was evaluated through standard deviation (SD), coefficient of variation (CV) and interquartile range (IQR). The percentage of time in range (% TIR), 126-139 mg/dL (TIR2) and 140-199 mg/dL (TIR3) were calculated. Shotgun metagenomics sequencing was applied to study gut microbiota taxonomy and functionality.

RESULTS: Increased glycemic variability (SD, CV and IQR) was observed among subjects with obesity in parallel to increased % TIR2 and % TIR3. REM sleep duration was independently associated with the % TIR3 (β=-0.339; p < 0.001) and glucose variability (SD, β=-0.350; p < 0.001). Microbial taxa from Christensenellaceae family (Firmicutes phylum) were positively associated with REM sleep and negatively with glucose continuous monitoring levels, while bacteria from Enterobacteriacea family and bacterial functions involved in iron metabolism showed opposite associations.

CONCLUSIONS: Decreased REM sleep duration was independently associated with a worse glucose profile. The associations of species from Christensenellaceae and Enterobacteriaceae families with REM sleep duration and continuous glucose values suggest an integrated picture of metabolic health.

PMID:37159524 | DOI:10.1210/clinem/dgad258

Plant J. 2023 May 9. doi: 10.1111/tpj.16269. Online ahead of print.

ABSTRACT

Wind, rain, herbivores, obstacles, neighbouring plants, etc. provide important mechanical cues to steer plant growth and survival. Mechanostimulation to stimulate yield and stress resistance of crops is of significant research interest, yet a molecular understanding of transcriptional responses to touch is largely absent in cereals. To address this, we performed whole-genome transcriptomics following mechano-stimulation of wheat, barley and the recently genome-sequenced oat. The largest transcriptome changes occurred ±25 min after touching, with the majority of genes being upregulated. While most genes returned to basal expression level by 1-2h in oat, many genes retained high expression even 4 h post-treatment in barley and wheat. Functional categories like transcription factors, kinases, phytohormones and Ca2+ -regulation were affected. Also cell wall-related genes involved in (hemi)cellulose, lignin, suberin and callose biosynthesis were touch-responsive, providing molecular insight into mechanically-induced changes in cell wall composition. Furthermore, several cereal-specific transcriptomic footprints were identified that were not observed in Arabidopsis. In oat and barley, we found evidence for systemic spreading of touch-induced signalling. Finally, we provide evidence that both jasmonic acid (JA)-dependent and JA-independent pathways underlie touch-signalling in cereals, providing a detailed framework and marker genes for further study of (a)biotic stress responses in cereals.

PMID:37159480 | DOI:10.1111/tpj.16269

Biotechnol Bioeng. 2023 May 9. doi: 10.1002/bit.28421. Online ahead of print.

ABSTRACT

Fermentation employing Saccharomyces cerevisiae has produced alcoholic beverages and bread for millennia. More recently, S. cerevisiae has been used to manufacture specific metabolites for the food, pharmaceutical, and cosmetic industries. Among the most important of these metabolites are compounds associated with desirable aromas and flavors, including higher alcohols and esters. Although the physiology of yeast has been well-studied, its metabolic modulation leading to aroma production in relevant industrial scenarios such as winemaking is still unclear. Here we ask what are the underlying metabolic mechanisms that explain the conserved and varying behavior of different yeasts regarding aroma formation under enological conditions? We employed dynamic flux balance analysis (dFBA) to answer this key question using the latest genome-scale metabolic model (GEM) of S. cerevisiae. The model revealed several conserved mechanisms among wine yeasts, for example, acetate ester formation is dependent on intracellular metabolic acetyl-CoA/CoA levels, and the formation of ethyl esters facilitates the removal of toxic fatty acids from cells using CoA. Species-specific mechanisms were also found, such as a preference for the shikimate pathway leading to more 2-phenylethanol production in the Opale strain as well as strain behavior varying notably during the carbohydrate accumulation phase and carbohydrate accumulation inducing redox restrictions during a later cell growth phase for strain Uvaferm. In conclusion, our new metabolic model of yeast under enological conditions revealed key metabolic mechanisms in wine yeasts, which will aid future research strategies to optimize their behavior in industrial settings.

PMID:37159408 | DOI:10.1002/bit.28421

STAR Protoc. 2023 May 8;4(2):102289. doi: 10.1016/j.xpro.2023.102289. Online ahead of print.

ABSTRACT

The current abundance of immunotherapy clinical trials presents an opportunity to learn about the underlying mechanisms and pharmacodynamic effects of novel drugs on the human immune system. Here, we present a protocol to study how these immune responses impact clinical outcomes using large-scale high-throughput immune profiling of clinical cohorts. We describe the Human Immune Profiling Pipeline, which comprises an end-to-end solution from flow cytometry results to computational approaches and unsupervised patient clustering based on lymphocyte landscape. For complete details on the use and execution of this protocol, please refer to Lyudovyk et al. (2022).1.

PMID:37159385 | DOI:10.1016/j.xpro.2023.102289

Virol J. 2023 May 8;20(1):91. doi: 10.1186/s12985-023-02048-5.

ABSTRACT

Viral hepatitis, the most common cause of inflammatory liver disease, affects hundreds of millions of people worldwide. It is most commonly associated with one of the five nominal hepatitis viruses (hepatitis A-E viruses). HBV and HCV can cause acute infections and lifelong, persistent chronic infections, while HAV and HEV cause self-limiting acute infections. HAV and HEV are predominantly transmitted through the fecal-oral route, while diseases transmitted by the other forms are blood-borne diseases. Despite the success in the treatment of viral hepatitis and the development of HAV and HBV vaccines, there is still no accurate diagnosis at the genetic level for these diseases. Timely diagnosis of viral hepatitis is a prerequisite for efficient therapeutic intervention. Due to the specificity and sensitivity of clustered regularly interspaced short palindromic repeat (CRISPR)/CRISPR-associated sequences (Cas) technology, it has the potential to meet critical needs in the field of diagnosis of viral diseases and can be used in versatile point-of-care (POC) diagnostic applications to detect viruses with both DNA and RNA genomes. In this review, we discuss recent advances in CRISPR-Cas diagnostics tools and assess their potential and prospects in rapid and effective strategies for the diagnosis and control of viral hepatitis infection.

PMID:37158910 | DOI:10.1186/s12985-023-02048-5

BMC Bioinformatics. 2023 May 8;24(1):188. doi: 10.1186/s12859-023-05309-w.

ABSTRACT

BACKGROUND: The limited knowledge of miRNA-lncRNA interactions is considered as an obstruction of revealing the regulatory mechanism. Accumulating evidence on Human diseases indicates that the modulation of gene expression has a great relationship with the interactions between miRNAs and lncRNAs. However, such interaction validation via crosslinking-immunoprecipitation and high-throughput sequencing (CLIP-seq) experiments that inevitably costs too much money and time but with unsatisfactory results. Therefore, more and more computational prediction tools have been developed to offer many reliable candidates for a better design of further bio-experiments.

METHODS: In this work, we proposed a novel link prediction model based on Gaussian kernel-based method and linear optimization algorithm for inferring miRNA-lncRNA interactions (GKLOMLI). Given an observed miRNA-lncRNA interaction network, the Gaussian kernel-based method was employed to output two similarity matrixes of miRNAs and lncRNAs. Based on the integrated matrix combined with similarity matrixes and the observed interaction network, a linear optimization-based link prediction model was trained for inferring miRNA-lncRNA interactions.

RESULTS: To evaluate the performance of our proposed method, k-fold cross-validation (CV) and leave-one-out CV were implemented, in which each CV experiment was carried out 100 times on a training set generated randomly. The high area under the curves (AUCs) at 0.8623 ± 0.0027 (2-fold CV), 0.9053 ± 0.0017 (5-fold CV), 0.9151 ± 0.0013 (10-fold CV), and 0.9236 (LOO-CV), illustrated the precision and reliability of our proposed method.

CONCLUSION: GKLOMLI with high performance is anticipated to be used to reveal underlying interactions between miRNA and their target lncRNAs, and deciphers the potential mechanisms of the complex diseases.

PMID:37158823 | DOI:10.1186/s12859-023-05309-w