Biology subjects

Pandey, M. K.

Publications and source records attributed to Pandey, M. K..

12 recordsLinked to original sources

bioRxiv2025

Whole genome sequencing-based multi-locus association mapping for kernel iron, zinc and protein content in groundnut

Malnutrition is a major global challenge, especially in the developing regions, where improving the nutritional content of staple crops is a significant step towards alleviating hidden hunger. Groundnut, a nutrient rich legume contains several mineral nutrients, high protein, essential amino-acids and vitamins that are required for human health. In this study, multi-season phenotyping data for kernel iron (Fe), zinc (Zn) content and protein content (PC) and whole genome re-sequencing (WGRS) data on mini-core collection, were used to perform genome-wide association study (GWAS) analysis. Phenotypic variability analysis revealed a large variation in the Fe (7.6 - 42.8 ppm), Zn (10.9 - 62.4 ppm) and PC (12.7 - 33.6%). GWAS analysis identified a total of 15 marker-trait associations (MTAs) and 28 candidate genes for pooled season data, as well as 44 MTAs and 62 candidate genes for individual seasons. Key candidate genes like MYB transcription factor (Arahy.QI0PHV, Arahy.1I6ZSS), Zn finger MYM type protein, RING finger MYM type protein (Arahy.7P97F6, Arahy.9R964H, Arahy.I3B88T) and NAC domain protein (Arahy.LV3APC), associated with the Fe and Zn homeostasis pathway, genes related to protein homeostasis, such as protein kinase family protein (Arahy.4D7KBI), and E3 ubiquitin-protein ligase (Arahy.PE3CF6), were also identified within significant MTA regions. These findings provide basis for the detection and characterization of the possible candidate genes related to the nutritional quality traits. Single nucleotide polymorphism (SNP)-based KASP (Kompetitive Allele Specific Polymerase Chain Reaction) markers for 9 SNPs were designed and validated. Of these, three markers (snpAH00636, snpAH00641 and snpAH00644) showed polymorphism which could be deployed in the genomics-assisted breeding for the development of nutrient-rich groundnut varieties.

plant biology↗

bioRxiv2025

Genomic analysis uncovers unique haplotype signatures from subspecies and agronomic types associated with blanchability in groundnut

Blanchability, defined as the ease of seed coat removal after roasting, is a vital trait for enhancing processing efficiency and product quality in groundnut (Arachis hypogaea L.). To enable a comprehensive haplotype-level genetic dissection of this trait, SNPs derived from whole-genome resequencing (WGRS) were used to perform genome-wide association study (GWAS) using multi-locus models (BLINK and FarmCPU) on a diverse groundnut mini-core collection phenotyped across two crop seasons. A total of 26 significant SNP-trait associations (STAs) were identified across multiple chromosomes, with major loci on chromosomes Ah05, Ah06, and Ah17, some of which were further validated using KASP (Kompetitive Allele-Specific PCR) markers. Candidate genes, such as those involved in cell wall biosynthesis (e.g., galactoside 2-alpha-L-fucosyltransferase-like protein, protein kinase superfamily members, and glycerophosphoryl diester phosphodiesterase 3), were found to be within linkage disequilibrium (LD) of the identified STAs, suggesting their plausible association with blanchability. Haplo-pheno analyses identified superior high-blanchability haplotypes; Ah05HapBL3, Ah06HapBL5, Ah06HapBL10, and Ah17HapBL6, which were predominantly found in the fastigiata subspecies (including Valencia and Spanish bunch agronomic types) from South Asia and South America, while the low-blanchability haplotypes were from hypogaea subspecies (including Virginia runner and Virginia bunch agronomic types) from Africa. Overall, this study provides valuable insights for customizing blanchability through haplotype-based breeding of processing-grade cultivars thereby improving groundnut value chains to meet diverse industrial demands.

genomics↗

bioRxiv2025

Mapping Fusarium Wilt and Sterility Mosaic Disease Resistance-Associated Genomic Regions and Haplotype Variants in Pigeonpea

The occurrence of fusarium wilt and sterility mosaic disease in genial conditions causes significant yield losses in pigeonpea. The present genome-wide association study (GWAS) was employed on 176-genotype panel to identify candidate genomic regions associated with FW and SMD resistance in pigeonpea. A total of 869,447 filtered SNP markers were used for GWAS analysis. GWAS analysis identified significant genomic regions for FW on chromosomes 05, 10, and 11 and for SMD on chromosome 09. Four resistant sources, namely, ICP20096, ICP20097, ICPL87119 and ICP13304 were identified as a resistance source for both FW and SMD. Total 12 markers from chromosome 11 for FW and 4 markers from chromosome 09 for SMD were validated using the KASP genotyping approach. We have identified resistant haplotypes for FW on chromosome 10 and 11 and for SMD on chromosome 09. Moreover, we have identified four InDels for FW on chromosome 5 in Two component response regulator gene (Cc_11098) and four InDels for SMD on chromosome 9 in genes, namely, LRR and NB-ARC domain disease resistance protein (Cc_21069), Flavonoid 3, 5-hydroxylase (Cc_21070) respectively. For FW, Cc_10507586 region from chromosome 5 is identified in ICPL87119 and ICPL20096 donors. A region Cc_21637656 from chromosome 11 is identified in the ICPL87119 but not in the ICPL20096. Similarly, a region Cc_4438493 from chromosome 10 is identified in the ICPL20096 but not in the ICPL87119. For SMD, Cc_24131177 region is identified in both the SMD resistance donors (ICPL20096 and ICPL87119). Ccsmd04 region from chromosome 4 has been identified in ICPL87119 but not in the ICPL20096. These genomic regions can be brought together into single elite genetic background with the help of the markers identified in this study. The validated markers and donor lines in this study offer valuable tools and resources for the genetic improvement of pigeonpea cultivars with enhanced FW and SMD resistance.

genomics↗

bioRxiv2025

InDels in an intronic region of gene Ccsmd04 coding for dormancy/auxin-associated protein controls sterility mosaic disease resistance in pigeonpea

Sterility mosaic disease presents a significant challenge to pigeonpea cultivation in the Indian subcontinent, potentially leading to total crop failure. The development of diagnostic molecular markers for SMD resistance can aid in improving SMD-resistant varieties. In this context, a QTL-seq approach identified genomic regions associated with SMD resistance using a recombinant inbred line generated from ICP8863 x ICPL87119. In total, 6,105 high-confidence variants were identified in the genomic region, namely, smdCc04 based on the delta SNP index. A genomic region smdCc04 on chromosome Cc04 spans 3.2 Mb (9.3 - 12.5 Mb) comprised of 6 missense variants and eight indels. A total of 211 candidate genes were identified from this region. 1 bp insertion, 21 bp insertion, 9 bp deletion, and 3 bp insertion at different intronic positions in 22 susceptible line leads to downregulation of Dormancy/auxin associated protein (Ccsmd04) resulting in loss of signaling in disease resistance pathways. The identified sites recognize four important disease and plant growth related transcription factors. A total of 4 Indels and 8 SNPs were validated from smdCc04 genomic regions using whole genome re-sequencing data and KASP genotyping on resistant and susceptible pigeonpea lines respectively. These markers will be used in pigeonpea breeding programs.

genomics↗

bioRxiv2025

Genomic analysis reveals the interplay between ABA-GA in determining dormancy duration in groundnut

Groundnut is an important leguminous crop however; its productivity and seed quality are frequently reduced due to lack of fresh seed dormancy (FSD). To address this challenge, a mini-core collection of 184 accessions was phenotyped to identify donors in each agronomic type, in addition to analysing data on whole genome re-sequencing and multi-season phenotypic evaluations to identify stable marker-trait associations (MTAs) associated with FSD. Phenotypic analysis revealed substantial variability in dormancy durations, with days to 50% germination (DFG) ranging from 1 to 30 days. Multi-locus genome-wide association studies (ML-GWAS) identified 27 MTAs in individual seasons and 12 MTAs in pooled seasons data, respectively. Key candidate genes identified included Cytochrome P450 superfamily proteins, protein kinase superfamily proteins, and MYB transcription factors involved in the Abscisic acid (ABA) pathway, as well as F-box interaction domain proteins, ATP-binding ABC transporters, associated with the Gibberellic acid (GA) pathway. SNP-based KASP (Kompetitive Allele-Specific Polymerase chain reaction) markers for 12 SNPs were developed and validated, of these 6 markers (snpAH00577, snpAH00580, snpAH00582, snpAH00585, snpAH00586 and snpAH00588) showed polymorphism between dormant and non-dormant lines. Incorporating favourable dormant alleles into breeding strategies could enable the development of high-yielding cultivars with a dormancy period of 2-3 weeks.

genomics↗

bioRxiv2025

Identification of High Blanchability Donors, Candidate genes and Markers in Groundnut

Blanchability in groundnut, the ability of seeds to shed their seed coat (testa), is a trait of economic importance in the food processing industry, yet remains underexplored in breeding programs. This study aimed to assess blanchability in 184 accessions from the ICRISAT minicore collection and identify associated genomic regions, candidate genes, and molecular markers. Significant variability was observed over two seasons, with blanchability ranging from 3.98% to 70.08%. Ten genotypes, including ICG10890, ICG9507, ICG13982, and ICG297, exhibited good blanchability, with ICG297 emerging as a promising donor based on cluster analysis of blanchability and agronomic traits. Genome-wide association studies (GWAS) using the 58K Axiom_Arachis SNP array revealed 58 significant SNP-trait associations and important candidate genes such as isocitrate dehydrogenase and ubiquitin ligase, which influence seed coat structure and cell wall integrity. Nine SNPs were validated via allele mining, with four markers--on chromosomes A01 (snpAH00551), A06 (snpAH00554), B04 (snpAH00558), and B07 (snpAH00559), effectively distinguishing between high and low blanchability genotypes. These validated SNPs present valuable tools for genomics-assisted breeding. Overall, the findings is the first study contributing to a better understanding of the genomics and genetic basis of blanchability and offer resources for improving processing traits in groundnut.

genomics↗

bioRxiv2025

Novel Pan-ALDH Inhibitor KS100 Effectively Targets ALDH+/CD138- Stem-like Cells to Overcome Relapse in Multiple Myeloma

Multiple myeloma (MM), a clonal plasma cell disorder is the second most frequent hematological malignancy in the United States. This malignancy is characterized by a series of symptoms such as bone lesions, hypercalcemia, renal failure, and anemia. The current clinical drugs in the market are successful in treating multiple myeloma patients into remission but does not address relapse where a more aggressive phenotype of the cancer remains untreatable. We hypothesize that a small subset of multiple myeloma stem-like cells (MMSLCs) that overexpress aldehyde dehydrogenases (ALDH+) is the cause of the relapse. Overexpression of ALDH bolsters drug resistance via detoxification and stemness via the retinoic acid signaling pathway. The phenotype of MMSLCs is not yet known for certainty but there are a few well established markers such CD138 negative (CD138neg) cells that are known to overexpress ALDH. In this study, we target regular MM cells and bortezomib resistant ALDH+/CD138neg MMSLCs with a novel, potent, pan-ALDH inhibitor, KS100. Here we report KS100 effectively lowered ALDH expression in regular and bortezomib resistant ALDH+/CD138neg cells, MM cell viability as well as proteins associated with MMSLCs. Most importantly we showed that KS100 lowered ALDH+ populations in regular, bortezomib resistant and CD138neg cells via ALDEFLUOR assay.

molecular biology↗

bioRxiv2025

Highly Pathogenic Avian Influenza A (H5N1) Clade 2.3.2.1a virus infection in domestic cats, India, 2025

In January 2025, the highly pathogenic avian influenza A(H5N1) virus clade 2.3.2.1a infection was detected in domestic cats and whole-genome sequencing of two cat H5N1 isolates was performed using the Oxford Nanopore MinION sequencing platform. Phylogenetic analysis revealed the circulation of triple reassortant viruses in cats. Although cat viruses lacked classic mammalian adaptation markers they carried mutations associated with enhanced polymerase activity in mammalian cells and increased affinity for 2-6 sialic acid receptor suggesting their potential role in facilitating infection in cats. The identification of reassortant HPAI H5N1 clade 2.3.2.1a viruses in domestic cats in India highlights the urgent need for enhanced surveillance in domestic poultry, wild birds, and mammals, including humans, to track genomic diversity and molecular evolution of circulating strains.

microbiology↗

bioRxiv2024

Assembly of branched chain amino acid (BCAA) to toxic fibrils may be related to pathogenesis of Maple syrup urine disease (MSUD)

Inborn errors of metabolism (IEMs) are a group of diseases caused by mutations in single genes, leading to the buildup of metabolites that are typically toxic or disrupt normal cellular function. The etiological relation of metabolic disorders has been uncovered through the study of metabolite amyloids. Various metabolites that accumulate in IEMs have been reported to self-assemble into organized structures. These structures exhibit similar physicochemical properties as proteinaceous amyloid fibrils. In this context, our study illustrated the aggregation properties of Branched chain amino acid (BCAA) i.e. Isoleucine, Leucine and Valine that accumulate in Maple syrup urine disease (MSUD) to investigate their propensities to assemble into amyloid-like fibrils. The structural morphologies of BCAA were studied via. microscopic techniques like Scanning electron microscopy (SEM), optical microscopy and phase contrast microscopy. Further, characterization techniques were employed to understand the physicochemical properties of the self-assemblies and its underlying mechanism. The amyloid-like nature of these aggregates was confirmed using Thioflavin T (ThT) and Congo Red (CR) assays, indicating a possible cytotoxic effect. The MTT assay reveals BCAAs were cytotoxic and significantly decrease cell viability. Our study plays a key role in understanding the physicochemical properties of MSUD in association to amyloid disease, possibly paving the way for the development of therapeutic solutions in the future. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=122 SRC="FIGDIR/small/616096v1_ufig1.gif" ALT="Figure 1"> View larger version (33K): org.highwire.dtl.DTLVardef@13f26daorg.highwire.dtl.DTLVardef@10fdef5org.highwire.dtl.DTLVardef@f6e1d7org.highwire.dtl.DTLVardef@64f608_HPS_FORMAT_FIGEXP M_FIG C_FIG The self-assembly of BCAA-Ile, Leu, Val was investigated and the findings indicate that their aggregation may follow an amyloidogenic pathway.

bioengineering↗

bioRxiv2023

A new efficacious Mcl-1 inhibitor maximizes bortezomib and venetoclax responsiveness in resistant multiple myeloma cells

Despite a record number of clinical studies investigating various anti-cancer drugs, the 5-year survival rate for multiple myeloma (MM) patients in the United States is only 55%, and nearly all patients relapse. Poor patient outcomes demonstrate that myeloma cells are "born to survive," which means they can adapt and evolve following treatment. As a result, new therapeutic approaches to combat this survival mechanism and target treatment-resistant malignant cells are required. Mcl-1, an anti-apoptotic protein, is required for the development of MM and resistance to therapy. This study looks at the possibility of KS18, a Mcl-1 inhibitor derived from pyoluteorin, to treat resistant MM. We show that KS18 inhibits Mcl-1 selectively and promotes post-translational modifications, resulting in UPS-dependent Mcl-1 degradation. Our findings show that KS18-induced Mcl-1 degradation results in caspase-dependent apoptosis. Importantly, KS18 triggered apoptosis in MM patient samples and bortezomib-resistant cells, synergizing with venetoclax to boost apoptosis. Furthermore, KS18 inhibits colony formation in bortezomib-resistant cells. KS18 treated NSG mice displayed significant tumor shrinkage without significant toxicity after four weeks of therapy with a single acceptable dose each week, indicating its powerful anti-neoplastic and anti-resistance characteristics. This study strongly implies that KS18 may treat MM and provide new hope to patients who are experiencing recurrence or resistance. Key pointsO_LIGiven that KS18 is a robust Mcl-1 inhibitor that targets Mcl-1 efficiently, it has the potential to be a novel treatment for multiple myeloma. C_LIO_LIKS18 has shown promise in re-sensitizing myeloma cells to chemotherapy as well as in overcoming resistance to bortezomib, venetoclax, and ABT-737. C_LI

pharmacology and toxicology↗

bioRxiv2022

Development of a Novel Bruton's Tyrosine Kinase Inhibitor that exerts Anti-Cancer Activities Potentiates Response of Chemotherapeutic Agents In Multiple Myeloma Stem Cell-Like Cells

Despite recent improvements in multiple myeloma (MM) treatment, MM remains an incurable disease and most patients experience a relapse. The major reason for myeloma recurrence is the persistent stem cell-like population. It has been demonstrated that overexpression of Brutons tyrosine kinase (BTK) in MM stem cell-like cells is correlated with drug resistance and poor prognosis. We have developed a novel small BTK inhibitor, KS151, which is unique compared to other BTK inhibitors. Unlike ibrutinib, and the other BTK inhibitors such as acalabrutinib, orelabrutinib, and zanubrutinib that covalently bind to the C481 residue in the BTK kinase domain, KS151 can inhibit BTK activities without binding to C481. This feature of KS151 is important because C481 becomes mutated in many patients and causes drug resistance. We demonstrated that KS151 inhibits in vitro BTK kinase activities and is more potent than ibrutinib. Furthermore, by performing a semi-quantitative, sandwich-based array for 71-tyrosine kinase phosphorylation, we found that KS151 specifically inhibits BTK. Our western blotting data showed that KS151 inhibits BTK signaling pathways and is effective against bortezomib-resistant cells as well as MM stem cell-like cells. Moreover, KS151 potentiates the apoptotic response of bortezomib, lenalidomide, and panobinostat in both MM and stem cell-like cells. Interestingly, KS151 inhibits stemness markers and is efficient in inhibiting Nanog and Gli1 stemness markers even when MM cells were co-cultured with bone marrow stromal cells (BMSCs). Overall, our results show that we have developed a novel BTK inhibitor effective against the stem cell-like population, and potentiates the response of chemotherapeutic agents.

molecular biology↗

bioRxiv2019

Ectopic hepatocyte transplantation cures the pig model of tyrosinemia

The effectiveness of cell-based therapies to treat liver failure is limited by the diseased liver environment. Herein we provide preclinical proof-of-concept for the treatment of liver failure through hepatocyte transplantation into lymph nodes in a large-animal model of hereditary tyrosinemia type 1 (HT1), a metabolic liver disease caused by deficiency of fumarylacetoacetate hydrolase (FAH) enzyme. FAH-deficient pigs received autologous hepatocyte transplantation into mesenteric lymph nodes after ex vivo transduction with a lentiviral vector carrying the pig Fah gene. Hepatocytes showed early (6 hour) and durable (8 month) engraftment in lymph nodes, with reproduction of vascular and hepatic microarchitecture. Subsequently, hepatocytes migrated to and repopulated the native diseased liver. The corrected cells generated enough liver mass to clinically ameliorate disease as early as 97 days post-transplantation, with complete normalization of tyrosine levels and liver function tests. Integration site analysis defined the corrected hepatocytes in the liver as a subpopulation of hepatocytes in the lymph nodes, indicating that the lymph nodes served as a source for healthy hepatocytes to repopulate a diseased liver. Ectopic transplantation of hepatocytes cures the pig model of HT1 and presents a promising approach to the treatment of liver disease in patients with pre-existing liver damage and fibrosis.\n\nOne Sentence SummaryTransplantation of corrected hepatocytes in mesenteric lymph nodes can cure fatal metabolic liver disease by providing organized liver tissue and by repopulating the diseased liver in the pig tyrosinemia model.

molecular biology↗