@article {164790, title = {Comparative transcriptomic insights into iron deficiency response in contrasting rice varieties at the seedling stage reveal distinct response strategies and identify novel candidate genes}, journal = {Frontiers in Plant Science}, volume = {17}, year = {2026}, month = {12 March 2026}, abstract = {

Iron deficiency is a major constraint in rice cultivation, particularly under direct-seeded rice (DSR) systems, where aerobic soil conditions reduce iron availability in plant-accessible forms. In this study, the experiment was initiated with screening of 116 germplasm lines of two weeks old line under hydroponics iron-deficient and sufficient conditions. Based on morphological and SPAD (Soil Plant Analysis Development) values, two contrasting rice genotypes - RA23 (tolerant) and LalatMas (susceptible) were selected and investigated to determine the molecular basis of iron deficiency response through comparative transcriptome analyses. A substantial number of differentially expressed genes (DEGs) were identified in each genotype, revealing distinct transcriptional reprogramming associated with iron acquisition, transport, and homeostasis. Functional classification and enrichment analyses uncovered genotype-specific regulation of pathways related to iron ion transport, general defense and stimulus-response functions, and ADP-binding activity, indicating the involvement of signaling and regulatory proteins. A subset of candidate genes, including both known iron-responsive regulators and previously uncharacterized proteins, was further prioritized based on differential expression patterns, interaction predictions, structural features and expression profiles. Quantitative real-time PCR validation confirmed the expression patterns of selected DEGs, supporting their relevance in iron stress adaptation. Notably, the greater induction of iron transporters in LalatMas likely reflects its stronger compensatory drive to acquire iron relative to RA23. This study provides the first report of leaf-specific transcriptomic signatures associated with iron deficiency in rice and offers a valuable set of candidate genes for functional analysis and breeding of iron-efficient cultivars optimized for DSR and other nutrient-limited agroecosystems.

}, doi = {10.3389/fpls.2026.1764898}, url = {https://www.frontiersin.org/journals/plant-science/articles/10.3389/fpls.2026.1764898/full}, author = {Ananya Sinha and Mohd Fayaz and Siddharth Panda and Ramanathan Sowdhamini} } @article {166873, title = {Emerging strategies for computational identification of protein{\textendash}protein interaction hotspots}, journal = {Current Opinion in Structural Biology}, volume = {98}, year = {2026}, pages = {103241}, abstract = {

A small number of residues at protein{\textendash}protein interfaces, commonly referred to as hotspots, dominate binding free energy and play a decisive role in stabilizing protein complexes. Identifying these residues is central to understanding the energetic architecture of protein{\textendash}protein interactions and to developing strategies for therapeutic intervention. Although experimental approaches such as alanine scanning have provided critical insights, they are often impractical for large or dynamic systems. This has positioned computational approaches at the forefront of hotspot analysis. This review highlights recent developments in molecular dynamics simulations and machine-learning{\textendash}based predictors for hotspot identification, discusses current challenges, and outlines emerging directions in the field. Finally, we suggest that combining these complementary approaches could offer a powerful framework for capturing the dynamic and energetic complexity of protein interfaces, making hotspot predictions more robust and interpretable.

}, issn = {0959-440X}, doi = {https://doi.org/10.1016/j.sbi.2026.103241}, url = {https://www.sciencedirect.com/science/article/pii/S0959440X26000230}, author = {Aditi Pathak and Vikas Tiwari and Ramanathan Sowdhamini} } @article {164008, title = {GRAYU: graph-based database integrating Ayurvedic formulations, medicinal plants, phytochemicals and diseases}, journal = {frontiers}, volume = {16}, year = {2026}, month = {22 January 2026}, abstract = {

The translation of India{\textquoteright}s extensive traditional knowledge on indigenous medicinal plants into modern therapeutic solutions is contingent upon a systematic framework. While traditional Indian medicine offers a rich source of therapeutic leads, this knowledge is often not structured for modern computational analysis, creating a barrier to systematic drug discovery.
To this end, we present GRAYU, a curated and comprehensive online database that integrates data across multiple categories, connecting 1,039 traditional formulations to 12,743 indigenous plants, 129,542 phytochemicals, and 13,480 indicated diseases.\ 
GRAYU provides insights into 1,370,257 plant-phytochemical, 116,531 plant-disease, 2,389 plant-formulation, and 4,087 formulation-disease associations. We show potential applications on phytochemical analogs, sustainable plant substitution, and disease-network analysis, highlighting the potential of integrative graphs to decode shared molecular signatures and therapeutic networks across traditional Ayurvedic formulations.
GRAYU represents a user-friendly resource for researchers to investigate complex bio-associations and formulate novel therapeutic hypotheses, with insights from traditional Indian medicine. GRAYU organises reported associations and computational relationships and can hint at mechanistic causality or biological activity; however, all outputs require contextual interpretation and further experimental validation.

}, keywords = {Data integration, Drug repurposing, Endangered plants, Knowledge graph, Network pharmacology, Traditional foods}, doi = {https://doi.org/10.3389/fphar.2025.1727224}, author = {Sarthak Joshi and Aditi Pathak and Dheemanth Reddy Regati and Revathy Menon and Deepthi S. Ajith and Aditya Sheshadri and Neerja Viswanathan and Poulomi Ray and Vimarishi Koul and Pratishruti Panda and Shriya Anand Bhambore and Shailya Verma and Ananya Sinha and K. Mohamed Shafi and Murugavel Pavalam and Ramanathan Sowdhamini} } @article {154149, title = {BPS2025 - Structural network comparison of domains across remote homologs}, journal = {Biophysical Journal}, volume = {124}, year = {2025}, month = {13 February 2025}, pages = {215a-216a}, chapter = {215a}, abstract = {

Protein domains serve as essential structural and functional units within proteins, with their organization largely defined by a limited set of domain architectures. Traditional structural comparison metrics like RMSD, TM-score, and GDT scores focus on protein backbones and often fail to capture the subtleties of inter-domain interactions and intradomain communication, which are crucial for diverse protein functions. Our work employs the use of protein structural network (PSN) analysis, which includes main-chain and side-chain atoms to investigate homologous domains. The PSN is a node and edge representation of amino acid residues, where an edge is defined between a pair of nodes (residues) that are within the interaction distance threshold. We examined the homologous domain pairs, in association with another homologous domain pair within and across proteins (type 1 and 2), vs. homologous domain pairs connected to structurally unrelated domains (type 2) by comparing their PSN. The study revealed significant variability in the network parameters (like degree change, hub preservation) between these types of domain comparisons. These findings may suggest mechanisms of having different domain functionality and structural integrity albeit maintaining similar structures. Furthermore, through graph spectral analysis, the networks of domain pairs in different types were studied to understand residue organization within individual domains and how the domain interaction partnership affects the domain structure and function. The network of two domains interacting permanently and transiently was also studied to reveal striking differences in their interfaces and beyond. This study would pave to better understand domain interactions in monomeric multi-domain proteins and eventually enable better homology differentiation of domains, thereby shedding light of folding of small multi-domain proteins.

}, doi = {10.1016/j.bpj.2024.11.1190}, url = {https://www.cell.com/biophysj/fulltext/S0006-3495(24)01914-3}, author = {Sidhanta Swayam Prakash Das and Vasam Manjveekar Prabantu and Ramanathan Sowdhamini and Narayanaswamy Srinivasan} } @article {158496, title = {Uncovering the transcription factors and metabolic pathways unique to proso millet and foxtail millet under salt stress through a comparative transcriptome approach}, year = {2025}, abstract = {

Salt stress causes major losses to crop production all over the globe. Millets being the climate-resilient crop possess the potential to overcome adverse abiotic stress conditions including salinity in comparison with other crops. Molecular level understanding of gene expressions that confer resistance to salt stress will increase food production as well as security. In addition to climatic resilient properties, they provide a high level of protein as well as important minerals like magnesium, phosphorus, and iron. In this study, we have compared the salt resistance responsible genes between proso millet and foxtail millet. The findings of this study compare the responses of foxtail and proso millets to salt stress and reveal a common metabolic network with 137 metabolic pathways that support salt tolerance. Pathways such as amino sugar and nucleotide sugar metabolism, phenylpropanoid biosynthesis, and different fundamental metabolism and energy-generating routes are examples of shared metabolic pathways. Salt stress signal conversion and energy metabolism under stress are both explained by the shared "Calcium signaling pathway" and "Oxidative phosphorylation pathway", respectively. Both species have distinctive metabolic pathways, which may indicate that they have each evolved differently in response to environmental forces. Notably, the species-specific transcription factors such as\ HD-ZIP\ and\ NAC\ in foxtail millet, and bHLH, ERF, and MYB-related in proso millet, highlight unique regulatory networks tailored to their environmental adaptations. The study also identified important transcription factors, including\ WRKY,\ bHLH,\ GRAS,\ Dof, and\ C3H, emphasizing their potential roles in increasing salinity tolerance and modifying stress responses. The enzymatic landscape includes both typical and unusual enzymes that take part in various pathways and are essential for metabolic adaptation.

}, keywords = {Proso millet {\textperiodcentered} Foxtail millet {\textperiodcentered} Metabolic pathways {\textperiodcentered} Transcription factor {\textperiodcentered} And abiotic stress}, doi = {10.1007/s44372-025-00237-w}, url = {https://link.springer.com/article/10.1007/s44372-025-00237-w}, author = {Anitha Ravichandran and Saranya Nallusamy and Selva Babu Selvamani and Ramanathan Sowdhamini} }