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Singh, M. P.

Publications and source records attributed to Singh, M. P..

11 recordsLinked to original sources

An open field phenomics resource for multimodal maize yield prediction across divergent environments

Temporal drone phenotyping captures crop development, but irregular flight schedules complicate comparisons across environments. We release curated imagery from 356 flights across 19 Genomes to Fields environments containing 1,180 maize (Zea mays L.) hybrids. To evaluate its utility, we integrated functional principal components of vegetation index and weather trajectories with genomic information. Combinined genomic and phenomic kernels improved yield prediction, reaching correlations up to r = 0.501 for held-out hybrids in environments represented in training and 0.408 when environments were also withheld. Accumulated growing degree days offered no consistent predictive advantage over days after planting, and weather contributed modest, task-dependent gains. A transformer neural process learned directly from irregular observations, serving as a novel application of neural process models in agriculture. Mapping vegetation index functional principal components identified recurrent quantitative trait loci on chromosomes 3 and 7. This resource and its reproducible analyses guide the use of temporal spectral data for crop prediction and genetic discovery.

plant biology↗

Gene-by-Environment Interaction Significantly Drives Bacterial Endophyte Communities in Maize Stalks

1.BackgroundMany microbes are known to boost the performance of crop plants, and their use as crop treatments ("biologicals") is an active area of research and commercialization. Although many identified microbes can boost plant production under laboratory settings, most fail to translate to field settings, and even the ones that are commercialized are often unreliable. While many factors likely underlie these issues, one that has been underexplored is the idea that interactions between plants and microbes can vary across both different host genetics and different environments, and that specific combinations of host and environment can result in very different microbial outcomes. ResultsTo quantify how a plant microbiome can change across host genotype and environment and to determine the relative importance of these factors, we sampled maize stalks from 20 specific hybrid varieties grown at 15 locations in the United States. Using 16S rRNA gene sequencing, we find that the stalk microbiome is highly variable, with a handful of bacterial taxa conserved at broader taxonomic levels (Phylum, Class) and almost none at finer levels (Genus, Species). Local environment and gene-by-environment interactions both had consistently large and significant effects on the microbial community (measured by alpha-and beta-diversity summary statistics, individual taxa, and inferred functional capacity), whereas host genotype had little to no consistent effect across environments. We also identified specific soil factors (pH and potassium) as the most significant environmental drivers of the community, even though these communities were living inside the stalks. ConclusionsTaken together, our results indicate that while host genetics can significantly affect the stalk microbial community, these effects are almost entirely predicated on interactions with the environment. These results imply that reliable deployment of microbes for crop production will require significant investment in trials across many locations and genetic backgrounds, either to estimate the GxE effects directly or to screen for microbes whose effects are less dependent on these two factors.

microbiology↗

Erythrocytic plasma membrane calcium ATPase (PMCA4b) variations mediate redox imbalance to determine artemisinin sensitivity in malaria

Artemisinin resistance in Plasmodium falciparum remains a major public health challenge for the ongoing malaria elimination programs. Till now, artemisinin resistance is linked with the variations in the genome of P. falciparum which are mainly clustered in the Pfkelch13 gene. Several studies reported artemisinin resistance in the malaria endemic areas without finding any evidence of genetic variation in parasite for this occurrence. This study interrogated whether host genetic variations have any association with artemisinin sensitivity of malaria parasite. We investigated the relationship of 1) genetic variations in the human ATP2B4 gene and 2) the resultant surface expression of plasma membrane calcium ATPase (PMCA4b) with the intraerythrocytic levels of calcium, reactive oxygen species (ROS) and the resistance towards artemisinin in the intraerythrocytic parasite. This study found negative correlation of PMCA4b expression level with intraerythrocytic calcium and ROS levels. Further in-vitro growth assays revealed that artemisinin sensitivity is reduced in the parasites growing within the RBCs having low PMCA4b and high oxidative stress. Overall, this study highlights the strong association of host PMCA4b in cellular calcium mediated redox imbalance, which significantly contributes to artemisinin resistance in malaria parasite. Hence, this is the first study to document the effect of host variations on artemisinin sensitivity of the parasite. We further emphasize that many redox modulating RBC polymorphisms that are prevalent in malaria endemic areas could influence artemisinin resistance and can serve as potential biomarkers for predicting therapeutic response. Thus, detailed population specific research may provide new insights for personalized malaria treatment and may inform future drug development strategies. SignificanceThe human host and malaria parasite share a closely interconnected relationship hence host variations could influence parasite drug resistance. This study demonstrates that reduced PMCA4b expression, the primary calcium efflux pump in RBCs, significantly increases the erythrocytic calcium and reactive oxygen species (ROS) levels, thereby decreasing the P. falciparum growth as well as artemisinin sensitivity. Many ROS inducing RBC polymorphisms, such as sickle cell, thalassemia, G6PD deficiency, PMCA4b variations etc. have emerged as strong malaria protective traits in several studies in malaria endemic areas. But these traits could also influence artemisinin resistance and can serve as potential biomarkers for predicting therapeutic response and highlights the importance of host erythrocytes oxidative microenvironment surveillance in monitoring antimalarial drug resistance.

microbiology↗

PANOMIQ: A Unified Approach to Whole-Genome, Exome, and Microbiome Data Analysis

The integration of whole-genome sequencing (WGS), whole-exome sequencing (WES), and microbiome analysis has become essential for advancing our understanding of complex biological systems. However, the fragmented nature of current analytical tools often complicates the process, leading to inefficiencies and potential data loss. To address this challenge, we present PANOMIQ, a comprehensive software solution that unifies the analysis of WGS, WES, and microbiome data into a single, streamlined pipeline. PANOMIQ is designed to facilitate the entire analysis process from raw data to interpretable results. It is the fastest algorithm that can achieve results much more quickly compared to traditional pipeline approaches of WGS and WES analysis. It incorporates advanced algorithms for high-accuracy variant calling in both WGS and WES, along with robust tools for characterizing microbial communities. The softwares modular architecture allows for seamless integration of these diverse data types, enabling researchers to uncover complex interactions between host genomics and microbiomes. In this study, we demonstrate the capabilities of PANOMIQ by applying it to a series of datasets encompassing a wide range of applications, including disease association studies and environmental microbiome profiling. Our results highlight PANOMIQs ability to deliver comprehensive insights, significantly reducing the time and computational resources required for multi-omic analysis. By providing a unified platform for WGS, WES, and microbiome analysis, PANOMIQ offers a powerful tool for researchers aiming to explore the full spectrum of genomic and microbial diversity. This software not only simplifies the analytical workflow but also enhances the depth of biological interpretation, paving the way for more integrated and holistic studies in genomics and microbiology.

bioinformatics↗

ACSL4 activity drives TNBC metastasis by positively regulating Histone H3 Acetylation mediated SNAIL expression

Triple-Negative Breast Cancer (TNBC) has profound unmet medical need globally for its devastating clinical outcome associated with rapid metastasis and lack of targeted therapies. Recently, lipid metabolic reprogramming has emerged as a major driver of breast cancer metastasis. Here, we unveil a strong association between the heightened expression of fatty acid metabolic enzyme, acyl-CoA synthetase 4 (ACSL4) and TNBC, which is primarily attributed by the selective absence of progesterone receptor (PR). Loss of ACSL4 function, either through genetic ablation or pharmacological inhibition significantly reduces metastatic potential of TNBC. Global transcriptome analysis reveals that ACSL4 activity markedly influences the gene expression pattern associated with TNBC migration. Mechanistically, ACSL4 alters fatty acid oxidation (FAO) and cellular acetyl-CoA levels, leading to the hyper-acetylation of particularly H3K27Ac and H3K9Ac marks resulting in overexpression of SNAIL during the course of TNBC metastatic spread to lymph node and lungs. Further, human TNBC metastasis exhibits positive correlation between ACSL4 and SNAIL expression. Altogether, our findings provide new molecular insights regarding the intricate interplay between metabolic alterations and epigenetic modifications, intertwined to orchestrate TNBC metastasis and posit a rational understanding for the development of ACSL4 inhibitors as a targeted therapy against TNBC.

cancer biology↗

Harnessing genetic variations improving seedling vigor for successful crop establishment in deep sown direct-seeded rice

Improving seedling vigour remains key objective for breeders working with direct-seeded rice (DSR). To understand the genetic control of seedling vigour in deep sown DSR, combined genome-wide association mapping, linkage mapping, fine mapping, RNA-sequencing to identify candidate genes and validation of putative candidate genes was performed. Significant phenotypic variations were observed among genotypes in both F3:4:5 and BC2F2:3 populations. The mesocotyl length showed significant positive correlation with %germination, root and shoot length. The 3.79 Mb region on chromosome 7 reported to be associated with mesocotyl elongation. RNA-seq data and RT-PCR results identified and validated seven potential candidate genes. The potential candidate gene, LOC_Os07g25150 codes for Myb-30-related transcription factor. The LOC_Os07g25150 codes for Myb 30-related transcription factor, LOC_Os07g17689 annotated as protein translation factor, LOC_Os07g17770 as tryptophanyl-tRNA synthetase, LOC_Os07g15440 as alanyl-tRNA synthetase family protein, LOC_Os07g24100 as retrotransposon protein and the remaining others as expressed proteins. The antagonistic relationship between Myb-30 and ethylene-mediated signalling (EIN-3) in regulating mesocotyl elongation have been observed. The functional characterization and knocking of LOC_Os07g25150 codes for Myb 30-related transcription factor may provide better understanding of the mechanism behind mesocotyl elongation. The four promising introgression lines with longer mesocotyl length, longer root length and semi-dwarf plant height have been identified.

genomics↗

PERK arm of UPR selectively regulates ferroptosis in colon cancer cells by modulating the expression of SLC7A11 (System Xc-)

Ferroptosis, a genetically and biochemically distinct form of programmed cell death, is characterised by an iron-dependent accumulation of lipid peroxides. Therapy-resistant tumor cells display vulnerability toward ferroptosis. Endoplasmic Reticulum (ER) stress and Unfolded Protein Response (UPR) play a critical role in cancer cells to become therapy resistant. Tweaking the balance of UPR to make cancer cells susceptible to ferroptotic cell death could be an attractive therapeutic strategy. To decipher the emerging contribution of ER-stress in the ferroptotic process, we observe that ferroptosis inducer RSL3 promotes UPR (PERK, ATF6, and IRE1), along with overexpression of cystine-glutamate transporter SLC7A11 (System Xc-). Exploring the role of a particular UPR arm in modulating SLC7A11 expression and subsequent ferroptosis, we notice that PERK is selectively critical in inducing ferroptosis in colorectal carcinoma. PERK inhibition reduces ATF4 expression and recruitment to the promoter of SLC7A11 and results in its downregulation. Loss of PERK function not only primes cancer cells for increased lipid peroxidation but also limits in vivo colorectal tumor growth, demonstrating active signs of ferroptotic cell death in situ. Further, by performing TCGA data mining and using colorectal cancer patient samples, we demonstrate that the expression of PERK and SLC7A11 is positively correlated. Overall, our experimental data indicate that PERK is a negative regulator of ferroptosis and loss of PERK function sensitizes colorectal cancer cells to ferroptosis. Therefore, small molecule PERK inhibitors hold huge promise as novel therapeutics and their potential can be harnessed against the apoptosis-resistant condition.

cancer biology↗

Identification of prognostic biomarkers for suppressing tumorigenesis and metastasis of Hepatocellular carcinoma through transcriptome analysis

Cancer is one of the deadliest diseases developed through tumorigenesis and could be fatal if reached at metastatic phase. The novality of present investigation is to explore the prognostic biomarkers in hepatocellular carcinoma (HCC) that could develop glioblastoma multiforme (GBM) due to metastasis. The analysis was done using RNA-Seq datasets for both HCC (PRJNA494560 and PRJNA347513) and GBM (PRJNA494560 and PRJNA414787) from Gene Expression Omnibus (GEO). This study identified 13 hub genes found to be overexpressed in both GBM and HCC. Promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability leading to improper chromosome segregation causing aneuploidy. A 13-gene predictive model was obtained and validated using KM plot. These hub genes could be prognostic biomarkers and potential therapeutic targets, inhibition of which could suppress tumorigenesis and metastasis.

bioinformatics↗

Demystifying the role of prognostic biomarkers in breast cancer through integrated transcriptome and pathway enrichment analyses

Breast cancer (BC) is the most commonly diagnosed cancer and the leading cause of death in women. There has been discovered an increasing number of molecular targets for BC prognosis and therapy. However, it is still urgent to identify new biomarkers. Therefore, we evaluated biomarkers that may contribute to the diagnosis and treatment of BC. We searched TCGA datasets and identified differentially expressed genes (DEGs) by comparing tumor (100 samples) and non-tumor (100 samples) tissues using the Deseq2 package. Pathway and functional enrichment analysis of the DEGs were done using DAVID (The Database for Annotation, Visualization, and Integrated Discovery) database. The protein-protein interaction (PPI) network was identified using the STRING database and visualized through Cytoscape software. Hub gene analysis of the PPI network was done using Cytohubba plugins. The associations between the identified genes and overall survival (OS) were analyzed using Kaplan-Meier plot. Finally, we have identified hub genes at the transcriptome level. A total of 824 DEGs were identified, which were mostly enriched in cell proliferation, signal transduction, and cell division. The PPI network comprised 822 nodes and 12145 edges. Elevated expression of the 5 hub genes AURKA, BUB1B, CCNA2, CCNB2, and PBK are related to poor OS in breast cancer patients. A promoter methylation study showed these genes to be hypomethylated. Validation through genetic alteration and missense mutations resulted in chromosomal instability leading to improper chromosome segregation causing aneuploidy. The enriched functions and pathways included the cell cycle, oocyte meiosis, and the p53 signaling pathway. The identified five hub genes in breast cancer have the potential to become useful targets for the diagnosis and treatment of breast cancer.

bioinformatics↗

In Silico insight to identify Potential Inhibitors of BUB1B from Mushroom bioactive compounds to Prevent Breast cancer metastasis

BUB1B (BUB1 Mitotic Checkpoint Serine/Threonine Kinase B) gene belongs to the spindle assembly checkpoint protein family, proven to be associated with many kinds of cancers. Protein kinases are crucial in metaphase to anaphase cellular transition. It is a primary element of spindle assembly checkpoint (SAC). This SAC is responsible for guarding the proper chromosomal segregation while any chromosomal instability hinders its normal functioning. The chromosomal instability may lead to cancer progression. And it occurs mainly due to overexpression of BUB1B in many cancer types especially in breast cancer metastasis. This could be controlled by designing proper inhibitor of this gene. For this purpose, there are proved existence of various mushroom compounds possessing some important medicinal properties with proven anti- cancerous effects. Proper screening and identification of molecules having these anti-cancerous effects and showing affinity against BUB1B with inhibition properties could be obtained from these compounds. So this study has incorporated 70 bioactive compounds (handpicked through literature mining) of distinct mushrooms that were considered and explored for identifying a suitable drug candidate. Their ADME/T properties were obtained to predict the drug-likeness of these 70 mushroom compounds based on Lipinskis rule of 5 (RO5). The screening of these bioactive compounds and subsequent molecular docking against BUB1B provided compounds with the best conformation-based binding affinity. The best 2 complexes, i.e., BUB1B- Lepiotaprocerin D and BUB1B-Peptidoglycan, were subjected to the molecular dynamics simulation. Both the complexes were observed for their affinity, stability, and flexibility in protein-ligand complex systems. The MD simulation study revealed that Lepiotaprocerin D has an energetically favorable binding affinity with BUB1B. Results showed that the formation of a hydrogen bond between ASN123, SER157 residue and Lepiotaprocerin D has strengthened the affinity of Lepiotaprocerin D with BUB1B. Hence, this study identified Lepiotaprocerin D as a potential and novel inhibitor for BUB1B that could be a plausible drug candidate for checking and controlling the spread of breast cancer metastasis.

bioinformatics↗

Comparison of two commercial ELISA kits for detection of rubella specific IgM and IgG antibodies

Enzyme linked immunosorbent assay (ELISA) plays an important role in laboratory confirmation of congenital rubella syndrome (CRS), postnatal rubella and seroprevalence studies in different populations. Variation of results are documented for samples tested by different commercial kits. The Enzygnost rubella ELISA, widely used in the WHO network, is expensive and not readily available. In the present study, performance of the Euroimmun ELISA was compared to the Enzygnost ELISA for detection of rubella specific IgM and IgG antibodies.\n\nTwo hundred and eighty five serum samples collected from suspected CRS patients identified through a recently initiated surveillance for CRS at six sentinel hospitals and 435 serum samples from a serosurvey of pregnant women from these sites, were available for testing of rubella specific IgM and IgG antibodies respectively. Qualitative agreement (concordance percentage and Cohens Kappa coefficient -{kappa}) was evaluated for both IgM and IgG assays. Bland - Altman plots were used to assess the difference in quantitative agreement for IgG titers.\n\nGood qualitative agreement between the two ELISA kits was observed for detection of both anti rubella IgM (94.7% agreement and k of 0.86) and IgG (96.3% agreement and k of 0.84). Sensitivity and specificity of Euroimmun assays compared to Enzygnost was 100% and 93.1% for IgM and 95.9% and 100% for IgG respectively. Bland - Altman analysis for paired quantitative results of rubella specific IgG yielded a mean difference of 0.781 IU/ml with majority of values (97.1%) within {+/-} 2 SD of the mean difference. Euroimmun ELISA provided on an average, higher titers as compared to Enzygnost.\n\nOur study findings suggest that Euroimmun ELISA may be considered for detection of rubella specific IgM in suspected CRS cases and rubella specific IgG in surveillance studies.

microbiology↗