phylaGAN: data augmentation through conditional GANs and autoencoders for improving disease prediction accuracy using microbiome data.

MOTIVATION: Research is improving our understanding of how the microbiome interacts with the human body and its impact on human health. Existing machine learning methods have shown great potential in discriminating healthy from diseased microbiome states. However, Machine Learning based prediction using microbiome data has challenges such as, small sample size, imbalance between cases and controls and high cost of collecting large number of samples. To address these challenges, we propose a deep learning framework phylaGAN to augment the existing datasets with generated microbiome data using a combination of conditional generative adversarial network (C-GAN) and autoencoder. Conditional generative adversarial networks train two models against each other to compute larger simulated datasets that are representative of the original dataset. Autoencoder maps the original and the generated samples onto a common subspace to make the prediction more accurate. RESULTS: Extensive evaluation and predictive analysis was conducted on two datasets, T2D study and Cirrhosis study showing an improvement in mean AUC using data augmentation by 11% and 5% respectively. External validation on a cohort classifying between obese and lean subjects, with a smaller sample size provided an improvement in mean AUC close to 32% when augmented through phylaGAN as compared to using the original cohort. Our findings not only indicate that the generative adversarial networks can create samples that mimic the original data across various diversity metrics, but also highlight the potential of enhancing disease prediction through machine learning models trained on synthetic data. AVAILABILITY AND IMPLEMENTATION: https://github.com/divya031090/phylaGAN.

Literature mining discerns latent disease-gene relationships.

MOTIVATION: Dysregulation of a gene's function, either due to mutations or impairments in regulatory networks, often triggers pathological states in the affected tissue. Comprehensive mapping of these apparent gene-pathology relationships is an ever-daunting task, primarily due to genetic pleiotropy and lack of suitable computational approaches. With the advent of high throughput genomics platforms and community scale initiatives such as the Human Cell Landscape project, researchers have been able to create gene expression portraits of healthy tissues resolved at the level of single cells. However, a similar wealth of knowledge is currently not at our finger-tip when it comes to diseases. This is because the genetic manifestation of a disease is often quite diverse and is confounded by several clinical and demographic covariates. RESULTS: To circumvent this, we mined ∼18 million PubMed abstracts published till May 2019 and automatically selected ∼4.5 million of them that describe roles of particular genes in disease pathogenesis. Further, we fine-tuned the pretrained bidirectional encoder representations from transformers (BERT) for language modeling from the domain of natural language processing to learn vector representation of entities such as genes, diseases, tissues, cell-types, etc., in a way such that their relationship is preserved in a vector space. The repurposed BERT predicted disease-gene associations that are not cited in the training data, thereby highlighting the feasibility of in silico synthesis of hypotheses linking different biological entities such as genes and conditions. AVAILABILITY AND IMPLEMENTATION: PathoBERT pretrained model: https://github.com/Priyadarshini-Rai/Pathomap-Model. BioSentVec-based abstract classification model: https://github.com/Priyadarshini-Rai/Pathomap-Model. Pathomap R package: https://github.com/Priyadarshini-Rai/Pathomap.

Integrating Patient-Reported Outcomes Into Prognostication in Gastroesophageal Cancer: Results of a Population-Based Retrospective Cohort Analysis.

BACKGROUND: Patient-reported outcomes measures (PROM) are self-reflections of an individual's physical functioning and emotional well-being. The Edmonton Symptom Assessment Scale (ESAS) is a simple and validated PRO tool of 10 common symptoms and a patient-reported functional status (PRFS) measure. The prognostic value of this tool is unknown in patients with gastroesophageal cancer (GEC). In this study, we examined the association between the ESAS score and overall survival (OS) in patients with GEC, the prognostication difference between ESAS and Eastern Cooperative Oncology Group (ECOG), and assessed the correlation between PRFS and the physician-reported ECOG performance status (PS). METHODS: The study was a retrospective cohort study of 211 patients with GEC with localized (stages I-III) and metastatic disease who completed at least one baseline ESAS prior to treatment. Patients were grouped into 3 cohorts based on ESAS score. OS was assessed using the Kaplan-Meier method, and the concordance index (c-index) was calculated for ESAS and physician-reported ECOG. The agreement between PRFS and physician-ECOG was also assessed. RESULTS: In total, 211 patients were included. The median age was 60.8 years; 90% of patients were ECOG PS 0-1; 38% of patients were stages I-III, while 62% were de novo metastatic patients. Median OS in low, moderate, high symptom burden (SB) patients' cohorts was 19.17 m, 16.39 mm, and 12.68 m, respectively (P < .04). The ability to predict death was similar between physician-ECOG and ESAS (c-index 0.56 and 0.5753, respectively) and PRFS and physician-ECOG (c-index of 0.5615 and 0.5545, respectively). The PS agreement between patients and physicians was 50% with a weighted Kappa of 0.27 (95% CI: 0.17-0.38). CONCLUSION: Patient's SB seems to carry a prognostic significance. ESAS and physician-reported ECOG exhibit comparable prognostic values. Physicians and patients can frequently have divergent opinions on PS. ESAS takes a patient-centered approach and should be encouraged in practice among patients with GEC as an additional tool for prognostication.

ReGeNNe: genetic pathway-based deep neural network using canonical correlation regularizer for disease prediction.

MOTIVATION: Common human diseases result from the interplay of genes and their biologically associated pathways. Genetic pathway analyses provide more biological insight as compared to conventional gene-based analysis. In this article, we propose a framework combining genetic data into pathway structure and using an ensemble of convolutional neural networks (CNNs) along with a Canonical Correlation Regularizer layer for comprehensive prediction of disease risk. The novelty of our approach lies in our two-step framework: (i) utilizing the CNN's effectiveness to extract the complex gene associations within individual genetic pathways and (ii) fusing features from ensemble of CNNs through Canonical Correlation Regularization layer to incorporate the interactions between pathways which share common genes. During prediction, we also address the important issues of interpretability of neural network models, and identifying the pathways and genes playing an important role in prediction. RESULTS: Implementation of our methodology into three real cancer genetic datasets for different prediction tasks validates our model's generalizability and robustness. Comparing with conventional models, our methodology provides consistently better performance with AUC improvement of 11% on predicting early/late-stage kidney cancer, 10% on predicting kidney versus liver cancer type and 7% on predicting survival status in ovarian cancer as compared to the next best conventional machine learning model. The robust performance of our deep learning algorithm indicates that disease prediction using neural networks in multiple functionally related genes across different pathways improves genetic data-based prediction and understanding molecular mechanisms of diseases. AVAILABILITY AND IMPLEMENTATION: https://github.com/divya031090/ReGeNNe.

An insight to treat cardiovascular diseases through phytochemicals targeting PPAR-α.

Peroxisome proliferator-activated receptor-α (PPAR-α) belonging to the nuclear hormone receptor superfamily is a promising target for CVDs which mechanistically improves the production of high-density lipid as well as inhibit vascular smooth muscle cell proliferation. PPAR-α mainly interferes with adenosine monophosphate-activated protein kinase, transforming growth factor-ß-activated kinase, and nuclear factor-κB pathways to protect against cardiac complications. Natural products/extracts could serve as a potential therapeutic strategy in CVDs for targeting PPAR-α with broad safety margins. In recent years, the understanding of naturally derived PPAR-α agonists has considerably improved; however, the information is scattered. In vitro and in vivo studies on acacetin, apigenin, arjunolic acid, astaxanthin, berberine, resveratrol, vaticanol C, hispidulin, ginsenoside Rb3, and genistein showed significant effects in CVDs complications by targeting PPAR-α. With the aim of demonstrating the tremendous chemical variety of natural products targeting PPAR-α in CVDs, this review provides insight into various natural products that can work to prevent CVDs by targeting the PPAR-α receptor along with their detailed mechanism.

Links between gut microbiome, metabolome, clinical variables and non-alcoholic fatty liver disease severity in bariatric patients.

BACKGROUND AND AIMS: Bacterial species and microbial pathways along with metabolites and clinical parameters may interact to contribute to non-alcoholic fatty liver disease (NAFLD) and disease severity. We used integrated machine learning models and a cross-validation approach to assess this interaction in bariatric patients. METHODS: 113 patients undergoing bariatric surgery had clinical and biochemical parameters, blood and stool metabolite measurements as well as faecal shotgun metagenome sequencing to profile the intestinal microbiome. Liver histology was classified as normal liver obese (NLO; n = 30), simple steatosis (SS; n = 41) or non-alcoholic steatohepatitis (NASH; n = 42); fibrosis was graded F0 to F4. RESULTS: We found that those with NASH versus NLO had an increase in potentially harmful E. coli, a reduction of potentially beneficial Alistipes putredinis and an increase in ALT and AST. There was higher serum glucose, faecal 3-(3-hydroxyphenyl)-3-hydroxypropionic acid and faecal cholic acid and lower serum glycerophospholipids. In NAFLD, those with severe fibrosis (F3-F4) versus F0 had lower abundance of anti-inflammatory species (Eubacterium ventriosum, Alistipes finegoldii and Bacteroides dorei) and higher AST, serum glucose, faecal acylcarnitines, serum isoleucine and homocysteine as well as lower serum glycerophospholipids. Pathways involved with amino acid biosynthesis and degradation were significantly more represented in those with NASH compared to NLO, with severe fibrosis having an overall stronger significant association with Superpathway of menaquinol-10 biosynthesis and Peptidoglycan biosynthesis IV. CONCLUSIONS: In bariatric patients, NASH and severe fibrosis were associated with specific bacterial species, metabolic pathways and metabolites that may contribute to NAFLD pathogenesis and disease severity.

Association Between MR Elastography Liver Stiffness and Histologic Liver Fibrosis in Children and Young Adults With Autoimmune Liver Disease.

BACKGROUND. Liver fibrosis is an important clinical endpoint of the progression of autoimmune liver disease (AILD); its monitoring would benefit from noninvasive imaging tools. OBJECTIVE. The purpose of this study was to assess the relationship between MR elastography (MRE) liver stiffness measurements and histologic liver fibrosis, as well as to evaluate the performance of MRE and biochemical-based clinical markers for stratifying histologic liver fibrosis severity, in children and young adults with AILD. METHODS. This retrospective study used an existing institutional registry of children and young adults diagnosed with AILD (primary sclerosing cholangitis [PSC], autoimmune sclerosing cholangitis [ASC], or autoimmune hepatitis [AIH]). The registry was searched to identify patients who underwent both a research abdominal 1.5-T MRI examination that included liver MRE (performed for registry enrollment) and a clinically indicated liver biopsy within 6 months of that examination. MRE used a 2D gradient-recalled echo sequence. One analyst measured mean liver shear stiffness (in kilopascals) for each examination. Laboratory markers of liver fibrosis (aspartate aminotransferase-to-platelet ratio index [APRI] and fibrosis-4 [FIB-4] score) were recorded. For investigational purposes, one pathologist, blinded to clinical and MRI data, determined histologic Metavir liver fibrosis stage. The Spearman rank order correlation coefficient was calculated between MRE liver stiffness and Metavir liver fibrosis stage. ROC analysis was used to evaluate diagnostic performance for identifying advanced fibrosis (i.e., differentiating Metavir F0-F1 from F2-F4 fibrosis), and sensitivity and specificity were calculated using the Youden index. RESULTS. The study included 46 patients (median age, 16.6 years [IQR, 13.7-17.8 years]; 20 female patients, 26 male patients); 12 had PSC, 10 had ASC, and 24 had AIH. Median MRE liver stiffness was 2.9 kPa (IQR, 2.2-4.0 kPa). MRE liver stiffness and Meta-vir fibrosis stage showed strong positive correlation (ρ = 0.68). For identifying advanced liver fibrosis, MRE liver stiffness had an AUC of 0.81, with sensitivity of 65.4% and specificity of 90.0%; APRI had an AUC of 0.72, with sensitivity of 64.0% and specificity of 80.0%; and FIB-4 score had an AUC of 0.71, with sensitivity of 60.0% and specificity of 85.0%. CONCLUSION. MRE liver stiffness measurements were associated with histologic liver fibrosis severity. CLINICAL IMPACT. The findings support a role for MRE in noninvasive monitoring of liver stiffness, a surrogate for fibrosis, in children and young adults with AILD. TRIAL REGISTRATION. ClinicalTrials.gov NCT03175471.

Size-induced exchange bias in single-phase CoO nanoparticles.

The tuning of exchange bias (EB) in nanoparticles has garnered significant attention due to its diverse range of applications. Here, we demonstrate EB in single-phase CoO nanoparticles, where two magnetic phases naturally emerge as the crystallite size decreases from 34.6 ± 0.8 to 10.8 ± 0.9 nm. The Néel temperature (TN) associated with antiferromagnetic ordering decreases monotonically with the reduction in crystallite size, highlighting the significant influence of size effects. The 34.6 nm nanoparticles exhibit magnetization irreversibility between zero-field cooled (ZFC) and field-cooled (FC) states belowTN. With further reduction in size this irreversibility appears well aboveTN, resulting in the absence of true paramagnetic regime which indicates the occurnace of an additional magnetic phase. The frequency-dependent ac-susceptibility in 10.8 nm nanoparticles suggests slow dynamics of disordered surface spins aboveTN, coinciding with the establishment of long-range order in the core. The thermoremanent magnetization (TRM) and iso-thermoremanent magnetization (IRM) curves suggest a core-shell structure: the core is antiferromagnetic, and the shell consists of disordered surface spins causing ferromagnetic interaction. Hence, the EB in these CoO nanoparticles results from the exchange coupling between an antiferromagnetic core and a disordered shell that exhibits unconventional surface spin characteristics.

Prevalence of human papillomavirus in head and neck cancer patients in India: a systematic review and meta-analysis.

BACKGROUND: Human papillomavirus (HPV) is increasingly recognized as a significant risk factor in the development of head and neck cancers (HNCs), with varying prevalence and impact. This study aims to systematically review and analyze the prevalence of HPV in HNCs in India, providing insights into regional variations. METHODS: A comprehensive literature search was carried out using PubMed, Embase, and Web of Science up to November 10, 2023. Inclusion criteria focused on original research reporting HPV-positive cases among HNC patients in India. We used Nested-Knowledge software, for screening, and data extraction. The modified Newcastle-Ottawa Scale was used for quality assessment of included studies. We pooled the prevalence of HPV among HNC patients and performed a random-effects model meta-analysis using R software (version 4.3). RESULTS: The search yielded 33 studies, encompassing 4654 HNC patients. The pooled prevalence of HPV infection was found to be 33% (95% CI: 25.8-42.6), with notable heterogeneity (I² = 95%). Analysis of subgroups according to geographical location indicated varying prevalence rates. Specifically, the prevalence was 47% (95% CI: 32.2-62.4) in the eastern regions and 19.8% (95% CI: 10.8-33.4) in the western regions. No evidence of publication bias was detected. CONCLUSION: The observed considerable regional disparities on the prevalence of HPV in HNC patients in India emphasizes the need for integrated HPV vaccination and screening programs in public health strategies. The findings underline the necessity for further research to explore regional variations and treatment responses in HPV-associated HNCs, considering the impact of factors such as tobacco use and the potential benefits of HPV vaccination.

Validation of no-biopsy pathway for the diagnosis of celiac disease in Asian adults: a multicenter retrospective study.

BACKGROUND AND AIM: While European Society of Pediatric Gastroenterology Hepatology and Nutrition advocates a no-biopsy pathway for the diagnosis of celiac disease (CeD) in children if IgA anti-tissue transglutaminase antibody (anti-tTG ab) titer is ≥10-fold upper limit of normal (ULN) and have a positive IgA anti-endomysial antibody (EMA); the data for anti-tTG Ab titer-based diagnosis of CeD in adults is still emerging. We planned to validate if IgA anti-tTG Ab titer ≥10-fold predicts villous abnormalities of modified Marsh grade ≥2 in Asian adult patients with CeD. METHODS: We recruited 937 adult patients with positive anti-tTG Ab from two databases, including AIIMS Celiac Clinic and Indian National Biorepository. The diagnosis of definite CeD was made on the basis of a positive anti-tTG Ab and the presence of villous abnormalities of modified Marsh grade ≥2. RESULTS: Of 937 adult patients with positive anti-tTG Ab, 889 (91.2%) showed villous abnormalities of modified Marsh grade ≥2. Only 47.6% of 889 adults with CeD had anti- tTG Ab titers of ≥10-fold. The positive predictive value (PPV) and specificity of anti tTG Ab titer ≥10-fold for predicting modified Marsh grade ≥2 were 99.8% and 98%, respectively. At anti-tTG Ab titer ≥11-fold, specificity and PPV were 100% for predicting villous abnormalities of modified Marsh grade ≥2. CONCLUSIONS: Approximately 50% of adults with CeD may benefit from the no biopsy pathway, reducing the health burden and risks of gastroscopy/anesthesia.

Impact of delay in the diagnosis on the severity of celiac disease.

BACKGROUND AND AIM: Celiac disease (CeD) has now become a global disease with a worldwide prevalence of 0.67%. Despite being a common disease, CeD is often not diagnosed and there is a significant delay in its diagnosis. We reviewed the impact of the delay in the diagnosis on the severity of manifestations of CeD. METHODS: We reviewed clinical records of 726 consecutive patients with CeD from the Celiac Clinic database and the National Celiac Disease Consortium database. We extracted specific data including the demographics, symptoms at presentation, time of onset of symptoms, time to diagnosis from the onset of the symptoms, and relevant clinical data including fold-rise in anti-tissue transglutaminase antibody (IgA anti-tTG Ab) and severity of villous and crypt abnormalities as assessed using modified Marsh classification. RESULTS: The median duration between the onset of symptoms and the diagnosis of CeD was 27 months (interquartile range 12-60 months). A longer delay in the diagnosis of CeD from the onset of symptoms was associated with lower height for age, lower hemoglobin, higher fold rise in IgA Anti tTG titers, and higher severity of villous and crypt abnormalities. About 18% of patients presented with predominantly non-gastrointestinal complaints and had a longer delay in the diagnosis of CeD. CONCLUSIONS: There is a significant delay in the diagnosis of CeD since the onset of its symptoms. The severity of celiac disease increases with increasing delay in its diagnosis. There is a need to keep a low threshold for the diagnosis of CeD in appropriate clinical settings.

Refining Field Cancerization: An Institutional Cohort Analysis of Patient Characteristics in a Validation Cohort.

BACKGROUND: Field cancerization is poorly defined in dermatology. The author group previously proposed and applied a classification system in an original cohort to risk-stratify patients with field cancerization. OBJECTIVE: Apply the authors' classification system within a validation cohort. METHODS: Patients with keratinocyte carcinoma history completed a survey regarding demographic information, medical history, and chemoprevention use. Patients were assigned a field cancerization class, and differences between validation and original cohorts were assessed. RESULTS: A total of 363 patients were enrolled (mean age 67.4; 61.7% male). After comparing validation and original cohorts, there were differences in age between class II (p = .02) and class IVb (p = .047), and differences in chemoprevention use in class III (p = .04). Similar to the original cohort, the validation cohort was associated with increases in total number of skin cancers in the last year (p < .001), 5 years (p < .001), lifetime (p < .001), years since first skin cancer (p < .001), and chemoprevention use (p < .001). In the validation cohort, there were increases in age (p = .03) and immunocompromised status (p = .04) with increasing class, which were not observed in the original cohort. CONCLUSION: Differences among field cancerization classes were similar in a validation cohort, further highlighting the importance of class-specific treatment and management.

Production performance, haematological parameters, serum biochemistry, and expression of HSP-70 in broiler chickens fed dietary ascorbic acid during heat stress.

An experiment was carried out to assess the efficacy of supplemental ascorbic acid (AA) on broiler chicken production performance, blood haematological profile, biochemical profile, and carcass traits under heat stress conditions. A total of 192-day-old broiler chicks were divided into four groups, each with six replicates of eight each (4 × 6 × 8). Four corn-based dietary treatments were formulated: T1 (control diet), T2 (T1 + AA at 200 mg/kg), T3 (T1 + AA at 400 mg/kg), and T4 (T1 + AA at 600 mg/kg) for a period of 42 days. Despite the high temperature and humidity, the 600 mg AA supplemental groups (T4) gained significantly (P ≤ 0.05) more body weight and had a higher feed intake and better feed conversion ratio (FCR) than the control group (T1). After 28 days of feeding the three AA-supplemented diets, antibody titres (humoral immune response) were significantly higher (P ≤ 0.05). The response to intradermally injected phyto-haemagglutinin (PHA-P), an index of the in vivo cell-mediated immune response, was found to be increased (P ≤ 0.05) in the 400 and 600 mg AA-supplemented groups after 35 days. Higher levels of AA (T4) supplementation significantly (P ≤ 0.05) improved haematological values such as haemoglobin (Hb), total erythrocyte count (TEC), total leukocyte count (TLC), and differential leukocyte count (DLC), heterophil:lymphocyte (H:L) in comparison to the control group (T1). The supplemented group improved the serum biochemical profile of the birds, with an increase (P ≤ 0.05) in total serum protein, albumin, and globulin and a decrease in serum cholesterol and corticosterone levels in the T4 group compared to the control group. Heat shock protein-70 (HSP-70) was gradually elevated after increasing the ascorbic acid concentration (P ≤ 0.05) at 14 and 21 days. As a result, it can be concluded that supplementing ascorbic acid at 600 mg/kg is beneficial for improving the performance, immunity, and blood haematological biochemical profile and upregulating the HSP-70 gene of broiler chickens under heat stress conditions.

Valorization of wheat straw into paper by ultrafiltered enzymatic bleaching approach.

In this study, the potential of ultrafiltered xylano-pectinolytic enzymatic bleaching approach was investigated, for manufacturing wheat straw-based paper. The enzymatic step was found to be most effective, with xylanase-pectinase dose of 4-1.7 IU/g pulp and time period of 180 min. The absorption spectra of the pulp free filtrate samples obtained after treatment of the pulp with ultrafiltered enzymes showed the removal of more impurities, in comparison to the treatment with crude enzymes. Microscopic analysis also showed the removal of lignin impurities in enzymatically bleached pulp samples. This bleaching approach using enzymes resulted in 27% reduction in ClO2 dose. Ultrafiltered enzymes treated pulp samples also showed improved quality-related parameters, and Gurley porosity, burst index, breaking length, double fold, tear index, and viscosity increased by 19.05, 13.70, 8.18, 29.27, 4.41, and 13.27%, respectively. The lignin content, TDS, TSS, BOD and COD values also decreased in the effluent samples obtained after enzymatic bleaching plus 73% chemical bleaching dose. The BOD and COD values of the effluent samples improved by 23.01 and 23.66%, respectively. Thus, indicating the potential of ultrafiltered xylano-pectinolytic enzymes in reducing pollution during bleaching of wheat straw. This is the first study, mentioning the efficacy of ultrafiltered enzymes in the bleaching of wheat straw-based paper with better optical-strength-related properties and effluent characteristics.

Dietary supplementation of ark clams protects gut health and modifies gut microbiota in d-galactose-induced aging rats.

BACKGROUND: Ark clams, a seafood abundant in various nutrients, are widely consumed worldwide. This study aimed to investigate the protective benefits of two common ark clams in Korea, Scapharca subcrenata (SS) and Tegillarca granosa (TG), on gut health in d-galactose (d-gal)-induced aging rats. RESULTS: Thirty-two Wistar rats (11 weeks old) were randomly allocated into four groups: a CON group (normal diet + saline intraperitoneal (i.p.) injection), a CD group (normal diet + d-gal i.p. injection), an SS group (normal diet with 5% SS supplementation + d-gal i.p. injection), and a TG group (normal diet with 5% TG supplementation + d-gal i.p. injection). After 12 weeks of treatment, histopathological results showed that gut barrier damage was alleviated in rats of the SS and TG groups, as evidenced by increases in mucus layer thickness and goblet cell numbers. Meanwhile, the two groups supplemented with ark clams showed an evident reduction in oxidative stress biomarkers (malondialdehyde and protein carbonyl content levels in the colon) and an increase in the immune-related factor (immunoglobulin A level in the plasma) in rats. The 16S ribosomal RNA analysis revealed that SS and TG ark clams significantly increased the proliferations of Bacteroidetes at the phylum level and Parabacteroides at the genus level. Additionally, the levels of the three main short-chain fatty acids in the cecal contents were also significantly increased in the SS and TG groups. CONCLUSION: Our results indicated a potent preventive effect of SS and TG ark clams on d-gal-induced gut injury, suggesting that ark clams may be a promising dietary component for intervening in aging. © 2023 Society of Chemical Industry.

Comparative transcriptome profiling of near isogenic lines PBW343 and FLW29 to unravel defense related genes and pathways contributing to stripe rust resistance in wheat.

Stripe rust (Sr), caused by Puccinia striiformis f. sp. tritici (Pst), is the most devastating disease that poses serious threat to the wheat-growing nations across the globe. Developing resistant cultivars is the most challenging aspect in wheat breeding. The function of resistance genes (R genes) and the mechanisms by which they influence plant-host interactions are poorly understood. In the present investigation, comparative transcriptome analysis was carried out by involving two near-isogenic lines (NILs) PBW343 and FLW29. The seedlings of both the genotypes were inoculated with Pst pathotype 46S119. In total, 1106 differentially expressed genes (DEGs) were identified at early stage of infection (12 hpi), whereas expressions of 877 and 1737 DEGs were observed at later stages (48 and 72 hpi) in FLW29. The identified DEGs were comprised of defense-related genes including putative R genes, 7 WRKY transcriptional factors, calcium, and hormonal signaling associated genes. Moreover, pathways involved in signaling of receptor kinases, G protein, and light showed higher expression in resistant cultivar and were common across different time points. Quantitative real-time PCR was used to further confirm the transcriptional expression of eight critical genes involved in plant defense mechanism against stripe rust. The information about genes are likely to improve our knowledge of the genetic mechanism that controls the stripe rust resistance in wheat, and data on resistance response-linked genes and pathways will be a significant resource for future research.

Ab-CoV: a curated database for binding affinity and neutralization profiles of coronavirus-related antibodies.

SUMMARY: We have developed a database, Ab-CoV, which contains manually curated experimental interaction profiles of 1780 coronavirus-related neutralizing antibodies. It contains more than 3200 datapoints on half maximal inhibitory concentration (IC50), half maximal effective concentration (EC50) and binding affinity (KD). Each data with experimentally known three-dimensional structures are complemented with predicted change in stability and affinity of all possible point mutations of interface residues. Ab-CoV also includes information on epitopes and paratopes, structural features of viral proteins, sequentially similar therapeutic antibodies and Collier de Perles plots. It has the feasibility for structure visualization and options to search, display and download the data. AVAILABILITY AND IMPLEMENTATION: Ab-CoV database is freely available at https://web.iitm.ac.in/bioinfo2/ab-cov/home. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

In silico evaluation of the impact of Omicron variant of concern sublineage BA.4 and BA.5 on the sensitivity of RT-qPCR assays for SARS-CoV-2 detection using whole genome sequencing.

BACKGROUND: Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant of concern (VoC) Omicron (B.1.1.529) has rapidly spread around the world, presenting a new threat to global public human health. Due to the large number of mutations accumulated by SARS-CoV-2 Omicron, concerns have emerged over potentially reduced diagnostic accuracy of reverse-transcription polymerase chain reaction (RT-qPCR), the gold standard diagnostic test for diagnosing coronavirus disease 2019 (COVID-19). Thus, we aimed to assess the impact of the currently endemic Omicron sublineages BA.4 and BA.5 on the integrity and sensitivity of RT-qPCR assays used for coronavirus disease 2019 (COVID-19) diagnosis via in silico analysis. We employed whole genome sequencing data and evaluated the potential for false negatives or test failure due to mismatches between primers/probes and the Omicron VoC viral genome. METHODS: In silico sensitivity of 12 RT-qPCR tests (containing 30 primers and probe sets) developed for detection of SARS-CoV-2 reported by the World Health Organization (WHO) or available in the literature, was assessed for specifically detecting SARS-CoV-2 Omicron BA.4 and BA.5 sublineages, obtained after removing redundancy from publicly available genomes from National Center for Biotechnology Information (NCBI) and Global Initiative on Sharing Avian Influenza Data (GISAID) databases. Mismatches between amplicon regions of SARS-CoV-2 Omicron VoC and primers and probe sets were evaluated, and clustering analysis of corresponding amplicon sequences was carried out. RESULTS: From the 1164 representative SARS-CoV-2 Omicron VoC BA.4 sublineage genomes analyzed, a substitution in the first five nucleotides (C to T) of the amplicon's 3'-end was observed in all samples resulting in 0% sensitivity for assays HKUnivRdRp/Hel (mismatch in reverse primer) and CoremCharite N (mismatch in both forward and reverse primers). Due to a mismatch in the forward primer's 5'-end (3-nucleotide substitution, GGG to AAC), the sensitivity of the ChinaCDC N assay was at 0.69%. The 10 nucleotide mismatches in the reverse primer resulted in 0.09% sensitivity for Omicron sublineage BA.4 for Thai N assay. Of the 1926 BA.5 sublineage genomes, HKUnivRdRp/Hel assay also had 0% sensitivity. A sensitivity of 3.06% was observed for the ChinaCDC N assay because of a mismatch in the forward primer's 5'-end (3-nucleotide substitution, GGG to AAC). Similarly, due to the 10 nucleotide mismatches in the reverse primer, the Thai N assay's sensitivity was low at 0.21% for sublineage BA.5. Further, eight assays for BA.4 sublineage retained high sensitivity (more than 97%) and 9 assays for BA.5 sublineage retained more than 99% sensitivity. CONCLUSION: We observed four assays (HKUnivRdRp/Hel, ChinaCDC N, Thai N, CoremCharite N) that could potentially result in false negative results for SARS-CoV-2 Omicron VoCs BA.4 and BA.5 sublineages. Interestingly, CoremCharite N had 0% sensitivity for Omicron Voc BA.4 but 99.53% sensitivity for BA.5. In addition, 66.67% of the assays for BA.4 sublineage and 75% of the assays for BA.5 sublineage retained high sensitivity. Further, amplicon clustering and additional substitution analysis along with sensitivity analysis could be used for the modification and development of RT-qPCR assays for detecting SARS-CoV-2 Omicron VoC sublineages.

Meta-QTL analysis in wheat: progress, challenges and opportunities.

Wheat, an important cereal crop globally, faces major challenges due to increasing global population and changing climates. The production and productivity are challenged by several biotic and abiotic stresses. There is also a pressing demand to enhance grain yield and quality/nutrition to ensure global food and nutritional security. To address these multifaceted concerns, researchers have conducted numerous meta-QTL (MQTL) studies in wheat, resulting in the identification of candidate genes that govern these complex quantitative traits. MQTL analysis has successfully unraveled the complex genetic architecture of polygenic quantitative traits in wheat. Candidate genes associated with stress adaptation have been pinpointed for abiotic and biotic traits, facilitating targeted breeding efforts to enhance stress tolerance. Furthermore, high-confidence candidate genes (CGs) and flanking markers to MQTLs will help in marker-assisted breeding programs aimed at enhancing stress tolerance, yield, quality and nutrition. Functional analysis of these CGs can enhance our understanding of intricate trait-related genetics. The discovery of orthologous MQTLs shared between wheat and other crops sheds light on common evolutionary pathways governing these traits. Breeders can leverage the most promising MQTLs and CGs associated with multiple traits to develop superior next-generation wheat cultivars with improved trait performance. This review provides a comprehensive overview of MQTL analysis in wheat, highlighting progress, challenges, validation methods and future opportunities in wheat genetics and breeding, contributing to global food security and sustainable agriculture.

Solanum nigrum L. in COVID-19 and post-COVID complications: a propitious candidate.

COVID-19 is caused by severe acute respiratory syndrome coronavirus-2, SARS-CoV-2. COVID-19 has changed the world scenario and caused mortality around the globe. Patients who recovered from COVID-19 have shown neurological, psychological, renal, cardiovascular, pulmonary, and hematological complications. In some patients, complications lasted more than 6 months. However, significantly less attention has been given to post-COVID complications. Currently available drugs are used to tackle the complications, but new interventions must address the problem. Phytochemicals from natural sources have been evaluated in recent times to cure or alleviate COVID-19 symptoms. An edible plant, Solanum nigrum, could be therapeutic in treating COVID-19 as the AYUSH ministry of India prescribes it during the pandemic. S. nigrum demonstrates anti-inflammatory, immunomodulatory, and antiviral action to treat the SARS-CoV-2 infection and its post-complications. Different parts of the plant represent a reduction in proinflammatory cytokines and prevent multi-organ failure by protecting various organs (liver, kidney, heart, neuro, and lung). The review proposes the possible role of the plant S. nigrum in managing the symptoms of COVID-19 and its post-COVID complications based on in silico docking and pharmacological studies. Further systematic and experimental studies are required to validate our hypothesis.