Biology subjects

Sowdhamini, R.

Publications and source records attributed to Sowdhamini, R..

At least 19 recordsLinked to original sources

bioRxiv2026

Comparative Modelling of Actin-Tropomyosin Interfaces

Tropomyosins are coiled-coil dimers that polymerize head-to-tail along actin filaments. They stabilize distinct filament populations and regulate the access of myosins and actin-binding proteins in both muscle and non-muscle contexts. Despite their central regulatory role, how filament length and isoform identity of different tropomyosin homologues might modulate actin affinity is not completely understood, especially across species. Here, we present a stepwise computational docking pipeline combining AlphaFold2-Multimer coiled-coil models, experimentally informed residue-level restraints, and pseudo-energy analysis via PPCheck to build and evaluate actin-tropomyosin co-polymer models for three isoforms: human TPM1 (hTPM1; 284 residues), human TPM4 (hTPM4; 248 residues), and Schizosaccharomyces pombe Cdc8 (SpCdc8; 161 residues). Interface energetics reveal a consistent hierarchy in which the shortest filament, SpCdc8, achieves the most stabilizing and residue-rich actin contacts, consistent with reduced cumulative geometric penalty along the actin helix. Among human isoforms, hTPM1 forms stronger interfaces with actin than hTPM4. The hTPM1-actin model also exhibits higher contact density and additional energetic hotspots, in agreement with the experimentally established slower exchange kinetics of TPM1 isoforms on actin filaments relative to TPM4. Hotspot mapping identifies conserved acidic residues at equivalent positions across all three isoforms, emphasizing the importance of electrostatic anchor points in maintaining interface integrity across diverse evolutionary contexts. Modeling of four temperature-sensitive SpCdc8 mutations (A18T, R21H, E31K and E129K) reveals that these substitutions substantially destabilize the coiled-coil dimer without significantly affecting actin interactions, suggesting that subtle regulatory failure arises from compromised longitudinal cable continuity rather than from direct loss of actin affinity. Taken together, our results support a hierarchical model of tropomyosin dimer stability, actin-tropomyosin recognition in which filament length imposes a geometric baseline on interface stability, onto which isoform-specific sequence evolution superimposes functional tuning. The tropomyosin homologues we studied appear to retain conserved electrostatic hotspots thereby providing a common structural scaffold across tissues and organisms.

bioinformatics↗

bioRxiv2026

HORI-EN: Atomic-level energetic profiling and higher-order network identification in protein structures

MotivationCharacterizing atomic-level stability and cooperative interaction networks is essential for understanding protein function and evolution. However, existing tools often lack the precision to integrate detailed physicochemical energies with higher-order graph-theoretic analyses. ResultsWe present HORI-EN, an updated implementation to the HORI framework, featuring hybrid energetic scoring (Physicochemical + Knowledge-Based) and a Normalized Interaction Score (NIS) based on cumulative distribution functions. HORI-EN identifies higher-order cliques of interacting residues, revealing cooperative stabilization networks. Validation on the SKEMPI v2 dataset demonstrates that HORI-EN shows discriminative performance in identifying mutational hotspots, achieving an ROC-AUC of 0.780 on the full dataset and 0.844 on a clean benchmark. Enrichment analysis indicates a 3.1-fold increase in precision for the top 1% of predictions. Furthermore, analysis of the residue interaction network recovers 77.4% of non-contacting hotspots by identifying one-hop bridging interactions to the partner chain. Beyond hotspot prediction, HORI-EN distinguishes native structures from decoys and captures conserved energetic signatures in evolutionary case studies of serine proteases and lipases. Availability and ImplementationThe web server is freely available at https://caps.ncbs.res.in/HORI-EN and source code is available at https://github.com/thesixeyedknight/HoriPy. Contactmini@ncbs.res.in

bioinformatics↗

bioRxiv2025

Structural network comparison of domains across remote homologues arising from different domain architectures

The homology of protein domains indicates an evolutionary relationship between them. Remote homologues, on the other hand, share very low sequence similarity while maintaining a highly similar structural topology. These similar structures can be compared using several metrices, but a comparison of networks built from amino acid residues to mimic non-covalent interactions provides a better understanding of their similarities or minute differences. Comparison of structurally related domains are studied to some extent, while the impact of domain combinations is poorly studied. In this study, several types of pairs of domains, arising from different multi-domain proteins were compared to understand the effect of cognate domain on the structural architecture of remote homologues. Several network parameters were compared among these domains. We found that an interacting domain of unrelated structure exerts higher structural and evolutionary pressure on the remote homologues, leading to structural embellishments and functional modifications. This exerted change is mediated by local rearrangements of the amino acid residues in the structure. Case studies were conducted to understand these effects. These results will assist in re-defining the homology among domains, which would rather help in better functional annotations and structural modelling.

bioinformatics↗

bioRxiv2025

GRAYU: Graph-based Database integrating Ayurvedic formulations, medicinal plants, phytochemicals and diseases

The translation of Indias 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 1039 traditional formulations to 12,949 indigenous plants, 129,542 phytochemicals, and 13,480 indicated diseases. It also provides insights into 1,382,362 plant-phytochemical, 116,824 plant-disease, 2,405 plant-formulation, and 4,087 formulation-disease associations. Case studies on phytochemical analogs, sustainable plant substitution, and disease-network pharmacology showcased 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 is available at https://caps.ncbs.res.in/GRAYU/.

bioinformatics↗

bioRxiv2025

SIRT2 attenuates stress-induced skeletal muscle atrophy by inhibiting glucocorticoid receptor signaling

Skeletal muscle atrophy occurs in several diseases and is associated with chronic stress. Studies indicate that glucocorticoid receptor signalling is the major signalling pathway that mediates stress-induced muscle degeneration. Although the glucocorticoid signalling pathway is relatively well characterized, there is a need to identify modulators of this pathway that may be useful for drug targeting to ameliorate muscle atrophy. SIRT2 is a mammalian Sirtuin isoform known to mediate the longevity benefits of calorie restriction and exercise. Currently, the role of SIRT2 in regulating stress-induced skeletal muscle atrophy is unclear. Our study found that SIRT2 is a critical regulator of muscle homeostasis and is required to protect against stress-induced muscle atrophy. Interestingly, SIRT2 levels are reduced during glucocorticoid-induced muscle atrophy in mice. SIRT2 depletion exacerbates glucocorticoid-induced reduction in myotube diameter and atrophy gene expression. In contrast, SIRT2 overexpression ameliorates myotube atrophy in primary myotubes. Our findings indicate that SIRT2 knockout mice are susceptible to glucocorticoid-induced muscle atrophy, while muscle-specific SIRT2-transgenic mice exhibit improved muscle function and are protected from glucocorticoid-induced atrophy. Mechanistically, SIRT2 binds to the glucocorticoid receptor to negatively regulate its activity, possibly via deacetylation of critical residues in its DNA-binding domain. Our findings suggest that SIRT2 activation may protect against glucocorticoid-induced skeletal muscle atrophy and serve as a potential therapeutic target for treating muscle atrophy.

pathology↗

bioRxiv2025

GenDiS3 database: census on prevalence of protein domain superfamilies of known structure in the entire sequence database

Despite the vast amount of sequence data available, a significant disparity exists between the number of protein sequences identified and the relatively few structures that have been resolved. This disparity highlights the challenge in structural biology to bridge the gap between sequence information and three-dimensional structural data, and the necessity for robust databases capable of linking distant homologues to known structures. Studies have indicated that there is a limited number of structural folds, despite the vast diversity of proteins. Hence, computational tools can enhance our ability to classify protein sequences, much before their structures are determined or their functions characterised, thereby bridging the gap between sequence and structural data. GenDiS is a repository with information on Genomic Distribution of protein domain superfamilies, involving a one-time computational exercise to search for trusted homologues of protein domains of known structures against the vast sequence database. We have updated this database employing advanced bioinformatics tools, including DELTA-BLAST for initial detection of hits and HMMSCAN for validation, significantly improving the accuracy of domain identification. Using these tools, over 151 million sequence homologues for 2060 superfamilies (SCOPe) were identified and 116 million out of them were validated as true positives. Through a case study on glycolysis-related enzymes, variations in domain architectures of these enzymes are explored, revealing evolutionary changes and functional diversity amongst these essential proteins. We present another case, LoG gene, where there one can tune-in and find significant mutations across the evolutionary lineage. The GenDiS database, GenDiS3, and the associated tools made available at https://caps.ncbs.res.in/gendis3/, offer a powerful resource for researchers in functional annotation and evolutionary studies. Database URL: https://caps.ncbs.res.in/gendis3/

bioinformatics↗

bioRxiv2025

Rational design and comparative docking and simulation of modified FLT3 inhibitors: A study on enhanced binding stability and inhibition potency

The FLT3 protein is a well-established therapeutic target in the treatment of Acute Myeloid Leukemia (AML), with its inhibition playing a crucial role in disease management. In this study, we identify and propose a novel FLT3 inhibitor that demonstrates superior binding affinity, stability, and pharmacokinetic properties compared to currently available inhibitors. We initially characterized the binding interactions of known FLT3 inhibitors through molecular docking and then strategically modified functional groups to enhance binding affinity, optimize drug-likeness, and minimize toxicity. The resulting analogue exhibits improved metabolic stability, lower toxicity, higher intestinal absorption, and superior permeability. Molecular dynamics simulations further confirm that the novel inhibitor forms stable and persistent interactions with FLT3, as evidenced by reduced conformational fluctuations and compact structural integrity. Free energy calculations reveal stronger ligand stabilization, while dynamic correlation analysis suggests enhanced engagement with critical residues, reinforcing its potential as an effective therapeutic agent. These findings highlight a promising candidate for further experimental validation and potential development in AML treatment.

cancer biology↗

bioRxiv2025

S9BactDB: A database for S9 family of proteases in bacterial genomes

S9 family proteins are serine proteases, divided into four subfamilies, involved in several functions associated with cell signalling, defence response and development. However, the annotation, characterization and statistical information are lacking. This is compounded by the huge number of bacterial genomes available. Hence, we have performed computational searches for S9 family peptidases as a step towards organising, curating the sequences and classifying into subfamilies. We have analysed annotated S9 family sequences from [~]32000 bacterial genomes/proteomes. All the curated information are presented as S9BacDB database (http://caps.ncbs.res.in/S9BactDB), provided in a user friendly way. The database provides various features such as information on the assemblies used (assembly, BioProject and BioSample details of each strain), the annotated POPs and their statistical distribution, unique domain architectures and the associated sequences and curated phylogenetic analysis. In addition, it provides the unique motifs and the associated information for Prolyl OligoPeptidases (POP) subtypes. An ML model is also integrated that can classify recognised sequences into a S9 sub family category. In conclusion, S9BactDb is a comprehensive platform that provides meticulously curated data on statistical/bioinformatics analysis of all S9 family proteins originating from fully sequenced bacterial genomes in the RefSeq database.

bioinformatics↗

bioRxiv2024

Syntaxin11 Deficiency Inhibits CRAC Channel Priming To Suppress Cytotoxicity And Gene Expression In FHLH4 Patient T Lymphocytes.

Mutations in Syntaxin11, a Q-SNARE, result in a fatal immune disorder known as familial hemophagocytic lymphohistiocytosis 4 (FHLH4) in human patients. A key diagnostic feature of FHLH4 is defective T and natural killer (NK) cell cytotoxicity. Here we show that Syntaxin11 directly binds and regulates Orai1, the pore forming subunit of calcium release activated calcium (CRAC) channels. CRAC channels enable store-operated calcium entry (SOCE) from the extracellular space and are crucial for granule exocytosis and nuclear factor of activated T cell (NFAT) dependent gene expression in activated lymphocytes. Syntaxin11 depletion strongly inhibited SOCE, CRAC currents, NFAT activation, interleukin-2 gene expression and degranulation in FHLH4 patient T lymphocytes and cell lines without affecting membrane trafficking. Remarkably, defects of cytolytic granule exocytosis as well as interleukin-2 expression could be reversed by ionomycin in patient T lymphocytes and a constitutively active, H134S, mutant of Orai1 rescued calcium entry in Syntaxin11 depleted cells. Further analyses showed that Syntaxin11 primes Orai1 for optimal on-site multimeric assembly which was Stim independent but required for gating. Priming of ion channel pore subunits is, therefore, a primary function of specific SNAREs which may have preceded their role in membrane trafficking and vesicle fusion.

cell biology↗

bioRxiv2024

Identification and study of Prolyl Oligopeptidases and related sequences in bacterial lineages

Proteases are enzymes that break down proteins, and serine proteases are an important subset of these enzymes. Prolyl oligopeptidase (POP) is a family of serine proteases (S9 family) that has the ability to cleave peptide bonds involving proline residues and it is unique for its ability to cleave various small oligopeptides shorter than 30 amino acids. The S9 family from the MEROPS database, is classified into four subfamilies based on active site motifs. These S9 subfamilies assume a crucial position owing to their diverse biological roles and potential therapeutic applications in various diseases. In this study, we have examined [~]32000 completely annotated bacterial genomes from the NCBI RefSeq Assembly database to identify annotated S9 family proteins. This results in the discovery of [~]53,000 bacterial S9 family proteins (referred to as POP homologues). These sequences are classified into distinct subfamilies through various machine-learning approaches and comprehensive analysis of their distribution across various phyla and species and domain architecture analysis are also conducted. Distinct subclusters and class-specific motifs of POPs were identified, suggesting differences in substrate specificity in POP homologues. This study can enable future research of these gene families that are involved in many important biological processes.

bioinformatics↗

bioRxiv2024

Exploration of Natural Products for Targeting IDH1 and IDH2 Mutations in Acute Myeloid Leukemia Through Ligand-Based Pharmacophore Screening and Molecular Dynamic Simulation Approaches

BackgroundMutations in isocitrate dehydrogenase 1 (IDH1) and 2 (IDH2) are prevalent drivers of acute myeloid leukemia (AML). While targeted therapies exist, resistance can emerge. This study explored the potential of natural products to identify novel dual IDH inhibitors. MethodsIn-silico screening of the COCONUT database was performed using Lipinskis Rule of Five. Pharmacophore modelling identified crucial features for IDH binding. Docking simulations with Glide (Schrodinger) assessed binding affinity, followed by MM-GBSA calculations for free energy estimation. The most promising candidate underwent ADME/T and toxicity analysis. Finally, molecular dynamics (MD) simulations evaluated the stability of protein-ligand complexes and binding interactions, followed by trajectory analysis using DCCM and PCA. ResultsThe study identified Ternstroside D (CNP0166496) as a potential dual inhibitor for IDH1 and IDH2 mutations. Docking simulations and MM-GBSA calculations predicted favourable binding affinities. MD simulations revealed stable protein-ligand complexes, and in-silico ADME/T analysis suggested good drug-like properties and a favorable safety profile for CNP0166496. ConclusionThis in-silico study provides compelling evidence for Ternstroside D (CNP0166496) as a promising dual inhibitor for IDH1 and IDH2 mutations in AML. Further in-vitro and in-vivo studies are warranted to validate these findings.

bioinformatics↗

bioRxiv2024

Understanding the roles of secondary shell hotspots in protein-protein complexes

Hotspots are interfacial residues in protein-protein complexes that contribute significantly to complex stability. Methods for identifying interfacial residues in protein-protein complexes are based on two approaches, namely, (a) distance-based methods, which identify residues that form direct interactions with the partner protein and (b) Accessibility Surface Area (ASA)-based methods, which identify those residues which are solvent-exposed in the isolated form of the protein and become buried upon complex formation. In this study, we introduce the concept of secondary shell hotspots, which are hotspots uniquely identified by the distance-based approach, staying buried in both the bound and isolated forms of the protein and yet forming direct interactions with the partner protein. From the analysis of the dataset curated from Docking Benchmark 5.5, comprising of 94 protein-protein complexes, we find that secondary shell hotspots are more evolutionarily conserved and have distinct Chou-Fasman propensities and interaction patterns compared to other hotspots. Finally, we present detailed case studies to show that the interaction network formed by the secondary shell hotspots is crucial for complex stability and activity. Further, they act as potentially allosteric propagators and bridge interfacial and non-interfacial sites in the protein. Their mutations to any other amino acid types cause significant destabilization. Overall, this study sheds light on the uniqueness and importance of secondary shell hotspots in protein-protein complexes.

bioinformatics↗

bioRxiv2024

The conserved biochemical activity and function of an early metazoan phosphatidylinositol 5 phosphate 4-kinase regulates growth and development.

The ability to co-ordinate function between multiple cells is a critical requirement for multi-cellularity. This co-ordination is mediated by hormones or growth factors, molecules secreted by one cell type that can convey information to the other cells and influence their behaviour. Hormone-dependent signalling is mediated by second messenger systems;phosphoinositides (PIs) generated by lipid kinase activity are one such key second messenger system. Phosphatidylinositol 5 phosphate 4-kinase (PIP4K) is a lipid kinase that phosphorylates phosphatidylinositol 5-phosphate (PI5P) to generate phosphatidylinositol 4,5 bisphosphate [PI(4,5)P2]. Following a comprehensive bioinformatics analysis of ca. 23296 proteomes covering the tree of life, we find that PIP4K is a metazoan-specific enzyme, although its homologs are also found in choanoflagellate genomes. To understand their function in early metazoans, we experimentally analysed the biochemical activity and physiological function of PIP4K from several early metazoans. We find that the PIP4K enzyme from an early branching metazoan sponge Amphimedon queenslandica (AqPIP4K), regarded as the earliest evolved metazoan, shows a biochemical activity highly conserved with human PIP4K; AqPIP4K is able to selectively phosphorylate PI5P to generate PI(4,5)P2 just as effectively as the human enzyme. Further, AqPIP4K was able to rescue the reduced cell size, growth and development phenotype in larvae of a null mutant in Drosophila PIP4K. These phenotypes are regulated through activity of the hormone insulin, acting via the cell surface insulin receptor, a member of the receptor tyrosine kinase family, that is unique to metazoans. Together, our findings indicate that in early metazoans, AqPIP4K is likely to function in a signal transduction pathway that is required for receptor tyrosine kinase signalling. Overall, our work defines PIP4K as a signal transduction motif required to regulate receptor tyrosine kinase signalling for intercellular communication in the earliest forms of metazoa.

biochemistry↗

bioRxiv2024

Sequence and structural analysis of adaptors of Toll-like receptor 4 sheds light on the evolutionary trajectory and functional emergence

1.Type 4 Toll-like receptors 4 (TLR4) recognise lipopolysaccharides (LPS) from bacteria as their conventional ligands and undergo downstream signalling to produce cytokines. They mediate the signalling either by the TIRAP-MyD88 complex or by the TRAM-TRIF complex. The MyD88 pathway is common to all other TLRs, whereas the TRAM-TRIF complex is largely exclusive to TLR4. We studied the TIR domain of TRAM and TRIF homologue proteins, that are crucial for downstream signalling. From our previous work on pan-genome-wide survey, we find Callorhincus milli to be the ancestral organism with both TRAM and TRIF proteins. To gain a deeper insight about the functioning of these proteins and comparison with the adaptor proteins in Homo sapiens, we performed TRAM and TRIF dimer docking to model the TRAM-TRIF complex of representative organisms across various taxa. These provide us insights to ascertain a possible interaction surface, calculate the energetics, electrostatic potential, and then employ Normal Mode Analysis (NMA) to examine fluctuating, interacting and specific residue clusters which can be important for the protein functioning in both organisms. We also performed molecular dynamics simulations of these complexes and cross validated the functionally important residues using network parameters. While the critical residues of TIRAP, TRIF, and MyD88 were preserved, we found that the important residues of TRAM signalling were not conserved in Callorhincus milli. This suggests the presence of functional TIRAP-MyD88 mediated TLR4 signalling and TRIF mediated TLR3 signalling in the ancestral species. The overall biological function of this signalling domain appears to be gradually acquired through the orchestration of several motifs through evolutionary scale.

bioinformatics↗

bioRxiv2023

Single-Site Phosphorylation Elicits Structural, Dynamic, and Accessibility Changes in Proteins at both Proximal and Distal Regions to the Phosphosite.

Phosphorylation, a fundamental cellular mechanism, intricately regulates protein function and signaling pathways. Our study employs extensive computational analyses on a curated dataset of phosphorylated and unphosphorylated protein structures to explore the multifaceted impact of phosphorylation on protein conformation. Our findings reveal that phosphorylation induces not only local changes at the phosphorylation site but also extensive alterations in distant regions, showcasing its far-reaching influence on protein structure-dynamics. Using Normal Mode Analysis (NMA), we investigate changes in protein flexibility post-phosphorylation, highlighting an enhanced level of structural dynamism. Through in-depth case studies on Polyubiquitin-B and Glycogen Synthase Kinase-3 Beta, we elucidate how phosphorylation at distinct sites leads to variable structural and dynamic modifications, potentially dictating functional outcomes. While phosphorylation largely preserves residue motion correlation, it significantly disrupts low-frequency global modes, presenting a dualistic impact on protein dynamics. We also explore alterations in the total accessible surface area (ASA), emphasizing region-specific changes around phosphorylation sites. This study sheds light on phosphorylation-induced conformational changes, dynamic modulation, and surface accessibility alterations, contributing to a comprehensive understanding of cellular regulation and suggesting promising avenues for therapeutic interventions.

biophysics↗

bioRxiv2023

Interfacial residues in protein-protein complexes are in the eyes of the beholder

Interactions between proteins are vital in almost all biological processes. The characterization of protein-protein interactions helps us understand the mechanistic basis of biological processes, thereby enabling the manipulation of proteins for biotechnological and clinical purposes. The interface residues of a protein-protein complex are assumed to have the following two properties: a) they always interact with a residue of a partner protein, which forms the basis for distance-based interface residue identification methods, and b) they are solvent-exposed in the isolated form of the protein and become buried in the complex form, which forms the basis for Accessible Surface Area (ASA)-based methods. The study interrogates this popular assumption by recognizing interface residues in protein-protein complexes through these two methods. The study shows that a few residues are identified uniquely by each method, and the extent of conservation, propensities and their contribution to the stability of protein-protein interaction varies substantially between these residues. The case study analyses showed that interface residues, unique to distance, participate in crucial interactions that hold the proteins together, whereas the interface residues unique to the ASA method have a potential role in the recognition, dynamics and specificity of the complex and can also be a hotspot. Overall, the study recommends applying both distance and ASA methods so that some interface residues missed by either method but crucial to the stability, recognition, dynamics and function of protein-protein complexes are identified in a complementary manner.

bioinformatics↗

bioRxiv2023

Sensing volatiles throughout the body: Geographic and tissue-specific olfactory receptor expression in the fig wasp Ceratosolen fusciceps

An essential adaptive strategy in insects is the evolution of olfactory receptors (ORs) to recognize important volatile environmental chemical cues. Our model species, Ceratosolen fusciceps, a specialist wasp pollinator of Ficus racemosa, likely possesses an OR repertoire that allows it to distinguish fig-specific volatiles in highly variable environments. Using a newly assembled genome-guided transcriptome, we annotated 63 ORs in the species and reconstructed the phylogeny of Ceratosolen ORs in conjunction with other hymenopteran species. Expression analysis showed that though ORs were mainly expressed in the antennae, 20 percent were also expressed in non-antennal tissues such as the head, thorax, abdomen, legs, wings, and ovipositor. Specific upregulated expression was observed in OR30C in the head and OR60C in the wings. We identified OR expression from all major body parts of C. fusciceps, suggesting novel roles of ORs throughout the body. Further examination of OR expression of C. fusciceps in widely separated geographical locations, i.e., south (urban) and northeast (rural) India, revealed distinct OR expression levels in different locations. This discrepancy likely parallels the observed variation in fig volatiles between these regions and provides new insights into the evolution of insect ORs and their expression across geographical locations and tissues.

genomics↗

bioRxiv2022

Transcriptome Data Analysis of Primary Cardiomyopathies Reveals Perturbations in Arachidonic Acid Metabolism

Cardiomyopathies are complex heart diseases with significant prevalence around the world. Among these, primary forms are the major contributor to heart failure and sudden cardiac death. As the high-energy demanding engine, the heart utilizes fatty acids, glucose, amino acid, lactate and ketone bodies as energy to meet its requirement. However, continuous myocardial stress and cardiomyopathies drive towards metabolic impairment that advances heart failure (HF) pathogenesis. So far, metabolic profile correlation across different cardiomyopathies remains poorly understood. In this study, we systematically explore metabolic differences amongst primary cardiomyopathies. By assessing the metabolic gene expression of all primary cardiomyopathies, we highlight the significantly shared and distinct metabolic pathways that may represent specialized adaptations to unique cellular demands. We utilized publicly available RNA-seq datasets to profile global changes in the above diseases and performed Gene set analysis (GSA). Our analysis demonstrates genes in arachidonic acid metabolism (AA) as significantly perturbated across cardiomyopathy. In particular, arachidonic acid metabolism gene PLA2G2A interacts with fibroblast marker genes and can potentially influence fibrosis during cardiomyopathy.

bioinformatics↗