PLAS-5k: Dataset of Protein-Ligand Affinities from Molecular Dynamics for Machine Learning Applications

Computational methods and recently modern machine learning methods have played a key role in structure-based drug design. Though several benchmarking datasets are available for machine learning applications in virtual screening, accurate prediction of binding affinity for a protein-ligand complex remains a major challenge. New datasets that allow for the development of models for predicting binding affinities better than the state-of-the-art scoring functions are important. For the first time, we have developed a dataset, PLAS-5k comprised of 5000 protein-ligand complexes chosen from PDB database. The dataset consists of binding affinities along with energy components like electrostatic, van der Waals, polar and non-polar solvation energy calculated from molecular dynamics simulations using MMPBSA (Molecular Mechanics Poisson-Boltzmann Surface Area) method. The calculated binding affinities outperformed docking scores and showed a good correlation with the available experimental values. The availability of energy components may enable optimization of desired components during machine learning-based drug design. Further, OnionNet model has been retrained on PLAS-5k dataset and is provided as a baseline for the prediction of binding affinities

Dissecting the genetic architecture of phenology affecting adaptation of spring bread wheat genotypes to the major wheat-producing zones in India

Spring bread wheat adaptation to diverse environments is supported by various traits such as phenology and plant architecture. A large-scale genome-wide association study (GWAS) was designed to investigate and dissect the genetic architecture of phenology affecting adaptation. It used 48 datasets from 4,680 spring wheat lines. For 8 years (2014–2021), these lines were evaluated for days to heading (DH) and maturity (DM) at three sites: Jabalpur, Ludhiana, and Samastipur (Pusa), which represent the three major Indian wheat-producing zones: the Central Zone (CZ), North-Western Plain Zone (NWPZ), and North-Eastern Plain Zone (NEPZ), respectively. Ludhiana had the highest mean DH of 103.8 days and DM of 148.6 days, whereas Jabalpur had the lowest mean DH of 77.7 days and DM of 121.6 days. We identified 119 markers significantly associated with DH and DM on chromosomes 5B (76), 2B (18), 7D (10), 4D (8), 5A (1), 6B (4), 7B (1), and 3D (1). Our results clearly indicated the importance of the photoperiod-associated gene (Ppd-B1) for adaptation to the NWPZ and the Vrn-B1 gene for adaptation to the NEPZ and CZ. A maximum variation of 21.1 and 14% was explained by markers 2B_56134146 and 5B_574145576 linked to the Ppd-B1 and Vrn-B1 genes, respectively, indicating their significant role in regulating DH and DM. The results provide important insights into the genomic regions associated with the two phenological traits that influence adaptation to the major wheat-producing zones in India

Genome-wide association mapping indicates quantitative genetic control of spot blotch resistance in bread wheat and the favorable effects of some spot blotch loci on grain yield

Spot blotch caused by the fungus Bipolaris sorokiniana poses a serious threat to bread wheat production in warm and humid wheat-growing regions of the world. Hence, the major objective of this study was to identify consistent genotyping-by-sequencing (GBS) markers associated with spot blotch resistance using genome-wide association mapping on a large set of 6,736 advanced bread wheat breeding lines from the International Maize and Wheat Improvement Center. These lines were phenotyped as seven panels at Agua Fria, Mexico between the 2013–2014 and 2019–2020 crop cycles. We identified 214 significant spot blotch associated GBS markers in all the panels, among which only 96 were significant in more than one panel, indicating a strong environmental effect on the trait and highlights the need for multiple phenotypic evaluations to identify lines with stable spot blotch resistance. The 96 consistent GBS markers were on chromosomes 1A, 1B, 1D, 2A, 3B, 4A, 5B, 5D, 6B, 7A, 7B, and 7D, including markers possibly linked to the Lr46, Sb1, Sb2 and Sb3 genes. We also report the association of the 2NS translocation from Aegilops ventricosa with spot blotch resistance in some environments. Moreover, the spot blotch favorable alleles at the 2NS translocation and two markers on chromosome 3BS (3B_2280114 and 3B_5601689) were associated with increased grain yield evaluated at several environments in Mexico and India, implying that selection for favorable alleles at these loci could enable simultaneous improvement for high grain yield and spot blotch resistance. Furthermore, a significant relationship between the percentage of favorable alleles in the lines and their spot blotch response was observed, which taken together with the multiple minor effect loci identified to be associated with spot blotch in this study, indicate quantitative genetic control of resistance. Overall, the results presented here have extended our knowledge on the genetic basis of spot blotch resistance in bread wheat and further efforts to improve genetic resistance to the disease are needed for reducing current and future losses under climate change

Vision, challenges and opportunities for a Plant Cell Atlas

With growing populations and pressing environmental problems, future economies will be increasingly plant-based. Now is the time to reimagine plant science as a critical component of fundamental science, agriculture, environmental stewardship, energy, technology and healthcare. This effort requires a conceptual and technological framework to identify and map all cell types, and to comprehensively annotate the localization and organization of molecules at cellular and tissue levels. This framework, called the Plant Cell Atlas (PCA), will be critical for understanding and engineering plant development, physiology and environmental responses. A workshop was convened to discuss the purpose and utility of such an initiative, resulting in a roadmap that acknowledges the current knowledge gaps and technical challenges, and underscores how the PCA initiative can help to overcome them.</jats:p

Comparative analysis of Magnesium Sulphate Versus Clonidine as an Adjuvant to Epidural Bupivacaine 0.5% in Lower Abdominal and Lower Limb Surgeries

Introduction: A prospective, randomized, controlled clinical trial was carried out to evaluate the effects ofMagnesium sulphate as an adjuvant to epidural bupivacaine and compared with clonidine along with epidural bupivacaine.Aims and Objective: Main objective to evaluate the efficacy of epidural magnesium sulphate&amp; clonidineused as an adjuvant to bupivacaine.Material and method: After approval from institutional ethical committee 60 patients undergoing lowerabdominal &amp;lower limb surgeries selected and divided in 2 groups Clonidine group and Magnesium group and different parameters observed.Observation: Co-administration of inj. Magnesium sulphate 50 mg. or Clonidine 3μg/kg (150μg maximum) to epidural bupivacaine produced predictable rapid onset of surgical anaesthesia without significant side effects. Addition of clonidine to epidural bupivacaine produced prolonged duration of analgesia with mild sedation compared to magnesium sulphate.Conclusion: From the study it is suggested that magnesium sulphate can be a useful alternative as anadjuvant to epidural bupivacaine without any side effects

Genome-Wide Association Mapping and Genomic Prediction of Anther Extrusion in CIMMYT Hybrid Wheat Breeding Program via Modeling Pedigree, Genomic Relationship, and Interaction With the Environment

Anther extrusion (AE) is the most important male floral trait for hybrid wheat seed production. AE is a complex quantitative trait that is difficult to phenotype reliably in field experiments not only due to high genotype-by-environment effects but also due to the short expression window in the field condition. In this study, we conducted a genome-wide association scan (GWAS) and explored the possibility of applying genomic prediction (GP) for AE in the CIMMYT hybrid wheat breeding program. An elite set of male lines (n = 603) were phenotype for anther count (AC) and anther visual score (VS) across three field experiments in 2017–2019 and genotyped with the 20K Infinitum is elect SNP array. GWAS produced five marker trait associations with small effects. For GP, the main effects of lines (L), environment (E), genomic (G) and pedigree relationships (A), and their interaction effects with environments were used to develop seven statistical models of incremental complexity. The base model used only L and E, whereas the most complex model included L, E, G, A, and G × E and A × E. These models were evaluated in three cross-validation scenarios (CV0, CV1, and CV2). In cross-validation CV0, data from two environments were used to predict an untested environment; in random cross-validation CV1, the test set was never evaluated in any environment; and in CV2, the genotypes in the test set were evaluated in only a subset of environments. The prediction accuracies ranged from −0.03 to 0.74 for AC and −0.01 to 0.54 for VS across different models and CV schemes. For both traits, the highest prediction accuracies with low variance were observed in CV2, and inclusion of the interaction effects increased prediction accuracy for AC only. In CV0, the prediction accuracy was 0.73 and 0.45 for AC and VS, respectively, indicating the high reliability of across environment prediction. Genomic prediction appears to be a very reliable tool for AE in hybrid wheat breeding. Moreover, high prediction accuracy in CV0 demonstrates the possibility of implementing genomic selection across breeding cycles in related germplasm, aiding the rapid breeding cycle

Multi-trait selection of bread wheat ideotypes for adaptation to early sown condition

Genotypes developed for a particular mega environment or management condition may not suit different management or specific local environments. Planting earlier than the recommended planting time is currently a new avenue to improve genotypic performance, supporting horizontal yield increases in the region when winter is shortening. In India, wheat-growers are looking at early planting because it can use residual soil moisture from monsoons and escape terminal heat stress. A BLUP-based multi-environmental stability analysis was conducted on three sets of genotypes across three consecutive years (2017, 2018, and 2019) under early and timely planting dates to identify genotypes for further breeding. A number of traits were studied - phenological (EGC, DTB, DTHD, DAYSMT, BTH, and GFD), plant stature (PH, HUS, and SpkLng), flag leaf (FLGLFL, FLGLFW, and FLGLFA), and yield traits (TGW and GRYLD). A significant genotypic effect was observed for all traits in the single environment analysis. A GEI was observed in the mixed-effect model, except for FLGLFA in season 2 and SpkLng in season 3. Residual components of variation were found to increase under early planting for all studied traits due to exposure of genotypes to early heat and a prolonged growing period. A higher GEI was observed in dissected phenological events such as BTH and GFD. Among phenological traits, it was found that DTB, GFD, and DAYSMT were strongly supporting selection gain throughout all seasons under early planting. The genotypes with a more extended vegetative period and grain filling period were tend to have higher grain yield and TGW under early planting

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Not AvailableMaydis leaf blight (MLB) resistance and days to flowering are the important yield determining traits in maize. Breeding for MLB resistance and days to flowering can be accelerated by understanding their genetics and identifying genomic regions contributing for their expression. Two F2s population with 338 and 349 individuals along with their recombinants inbred lines (RILs) having 283 and 277 individuals were developed from F1 crosses HKIPC4P × CML269 and ESM113 × P72clXbrasil1117 for genetic studies of MLB resistance and flowering. The populations along with their parents were screened under artificially inoculated conditions at hot-spot sites during 2015–17. Race O inoculum was artificially inoculated in the leaf whorl of each plant at 4-6 leaf stage. The inoculation was repeated after 8-10 days of first inoculation to avoid any chance of disease escape. The partial dominance in F1s, normal distribution patterns in F2s and RILs for both the traits has indicated their polygenic nature. Correlation analysis found negative and significant association (P≤0.001) between disease scores and days to flowering across the populations. Total 250 simple sequence repeats (SSR) markers, uniformly selected from all linkage groups were used for parental polymorphism survey between parents of the populations contrasting for target traits. Of total 250 SSRs, 122 (48.8% polymorphism) were identified as polymorphic between either of the parents. Sufficient genetic variation was observed within and between different F2s and RILs mapping populations. The information on inheritance, parental polymorphism survey and genetic materials developed will be useful for fine mapping and systematic breeding of targeted traits in tropical maize germplasm.Not Availabl