Human physiology is an ensemble of various biological processes spanning from intracellular molecular interactions to the whole-body phenotypic response. Systems biology endures to decipher these multi-scale biological networks and bridge the link between genotype to phenotype. The structure and dynamic properties of these networks are responsible for controlling and deciding the phenotypic state of a cell. Several cells and various tissues coordinate together to generate an organ level response which further regulates the ultimate physiological state. The overall network embeds a hierarchical regulatory structure, which when unusually perturbed can lead to undesirable pathophysiological state. At MetFlux, we have developed an Investigative Physiology Platform for specific states which integrates several data types from genomic to metabolomics to diagnostic biomarkers. The application of such an analysis is illustrated in the case of metabolic syndrome/NAFLD, Gut health and Skin pathophysiology. The work emphasizes the importance of integrating data structures, knowledge graphs, expert systems to physiological readouts, especially aligning multi-omics datasets.

Externalizing disorders (ED) are marked by impulsivity and aggression, often stemming from adverse childhood experiences. These experiences increase susceptibility to impulse control disorders in adulthood, though underlying biological mechanisms are not fully understood. Metabolomics offers insight into disease-related pathways, potentially identifying biomarkers for early ED diagnosis. This study aims to discover novel early-life metabolomic markers linked to neurodevelopment and cognitive regulation, forming a predictive biomarker panel for psychiatric vulnerability. Children under 18 with familial ED risk will be recruited from the c-VEDA cohort, which explores genomic impacts on neurodevelopment and vulnerability to externalizing disorders. Using LC-MS for global metabolomic profiling and GC-MS for Short Chain Fatty Acids (SCFA) and fatty acid analysis on plasma samples, results will be correlated with neurocognitive and MRI data to assess vulnerability to ED. This study uniquely examines early-life metabolomic signatures in relation to cognitive and neurodevelopmental markers, providing pioneering insights into ED susceptibility in India. By analyzing early-life metabolomic profiles, this research aims to establish an economical biomarker panel for screening ED risk, offering potential diagnostic and therapeutic applications for those susceptible to externalizing disorders.

With lifestyle-related metabolic disorders on the rise, effective personalized nutrition approaches are essential. Ayurveda offers a structured framework through the tridosha and prakriti system, classifying individuals into metabolic types—vata, pitta, and kapha—each with distinct physiological and metabolic profiles. Emerging research links prakriti types to specific nuclear receptors that regulate gene expression, impacting metabolic pathways, homeostasis, and phenotype. Studies associate prakriti with gene polymorphisms, inflammation markers, and oxidative stress pathways, suggesting a direct connection between an individual’s genetic profile and metabolic functions. This Ayurveda-based view aligns with metabolomics findings, providing a foundation for targeted health interventions. Additionally, Ayurvedic principles of Rasa (taste-based) therapies highlight variations in taste receptor interactions, affecting nutrient metabolism and bioavailability. By exploring these molecular interactions, we can better understand how diet influences genetic and metabolic pathways, aligning with personalized nutrikinetics. Combining Ayurveda with metabolomics insights promises a holistic approach to precision nutrition. This fusion supports developing tailored dietary interventions to enhance health outcomes, particularly in metabolic and lifestyle diseases.

This talk explores genetic influences on childhood obesity and metabolic syndrome (MetS). Findings highlight significant associations between obesity-related polygenic risk scores (PRS) and MetS markers, including BMI and waist circumference, with variations by lifestyle and sociodemographic factors such as dietary fiber intake and parental education. Notably, SNPs in the FTO and CETP genes emerge as key drivers of genetic predisposition to MetS. These results suggest that early risk identification using PRS, combined with targeted lifestyle interventions, may help mitigate long-term metabolic health risks in high-risk children.

Metabolomics and lipidomics are pivotal in understanding phenotypic variations beyond genomics. The workflow of experiment follows several interdependent phases. The scientific question determines the study model and the type of metabolite detection. Sample identity, preanalytics, sample matrix, confounders, sampling time, sample randomization, contingency plan, legal issues, and replication are important considerations in the study design phase. Metabolomics and lipidomics require special quality control and quality assurance procedures because of the many variables involved in sample preparation and analysis. However, quantification and comparability of mass spectrometry (MS)-derived data are challenging. Standardized assays can enhance data comparability, enabling applications in multi-center epidemiological and clinical studies. We evaluated the performance and reproducibility of the MxP® Quant 500 kit across 14 laboratories worldwide. Overall, the kit exhibited high reproducibility with a median coefficient of variation (CV) of 14.3%. CVs in NIST SRM 1950 reference plasma were below 25% and 10% for 494 and 138 metabolites, respectively. Comparisons with previous studies on the performance of MS-based kits (including AbsoluteIDQ p180 and Lipidyzer) revealed good concordance of reproducibility results and measured absolute concentrations in NIST SRM 1950 for most metabolites, except for fatty acids, confirming the validity of the MxP® Quant 500.

Atherosclerosis is a severe chronic inflammatory disease involving multiple cell types that causes plaques to accumulate in the arteries. Atherosclerotic plaques are rich in oxidized lipid and include many cell types, including macrophages and other immune cells, fibroblasts, endothelial and vascular smooth muscle cells all of which can secrete mediators. Essential human metabolic mediators, lipids are also linked to cancer, heart and kidney ailments, neurological and hepatic problems, and metabolic disorders. However, spatial information of lipid and protein mediators in plaques during disease development are limited. Therefore, using imaging mass spectrometry, we aim to analyze lipids and protein in plaques from hyperlipidemic mice fed a high fat diet. LIPIDMAPS software was employed for characterization of lipids by examining MS/MS fragments. Pathways enrichment analysis was performed using Lipid Pathway Enrichment Analysis. This study leverages to illuminate the intricate connections between lipid and protein with disease progression in atherosclerosis in male and female mice. These insights paving the way for precision interventions and transformative advancements in cardiovascular diseases.

T. gondii infection during pregnancy can cause abortion or congenital disease. Events in the maternal-foetal interface, where immunological changes occur, are critical in determining the pregnancy outcome. Several studies cover the serum biochemical/metabolic changes following T. gondii infection, but limited information exists concerning changes to the placental metabolome or the foetus while in utero. For the first time, this study covers the metabolomic profile and potential underlying mechanisms in the maternal-foetal interface, the developing foetus and maternal serum in BALB/c mice in a T. gondii congenital infection model. Results demonstrate the highest number of metabolite changes in the maternal serum, however a subset of these changes to tryptophan degradation pathway, arginine metabolic pathway was also found in the maternal-foetal interface and the developing foetus. In addition, some metabolites from microbiome origin including indoxylsulfate and 4-guanidinobutanoate were changed compared with the controls, suggesting the potential of T. gondii to change the host microbiome. However, preliminary metagenomics analysis did not demonstrate such changes, albeit in a different model of T. gondii infection. Comparison of alterations of metabolites between the developing foetus and the brain from adult mice born to infected mothers was carried out to determine whether the changes observed in early foetal life were still evident in later life. The most significant finding of this study is that increased kynurenine levels are found in early foetal life. This metabolite was found to be increased in the brains of adult mice with congenital T. gondii infection, but not in uninfected litter mates exposed to maternal-immune activation. This suggests that raised kynurenine levels in foetuses in utero might be maternally derived and short lived, but ultimately endogenously produced in congenitally infected mice. This metabolite has been implicated in psychoneurological diseases, but the consequences of kynurenine exposure in these circumstances remain to be determined.

Cholesterol is pivotal to mammalian lipid metabolism, and its dysregulation is associated with several human diseases. Physiologically, cholesterol is tightly regulated through the flux between cholesterol and cholesteryl esters (Fatty acid esters of cholesterol intended for storage and transport). Over the years, in vivo concentrations of cholesterol have been of important clinical significance and several mass spectrometry-based methods have been developed for detecting cholesterol and cholesteryl esters. However, due to their chemically inert nature, their extreme hydrophobicity, and poor ionization, these neutral lipids have often proved a challenge in developing lipidomics compatible liquid chromatography-mass spectrometry (LC-MS) methods to study them. To address this, we have developed a simple reverse-phase LC-MS method that is compatible with existing high-throughput lipidomics strategies and capable of identifying and quantifying cholesterol and cholesteryl esters from mammalian cells and tissues. Using this sensitive yet robust LC-MS method, we have profiled different mammalian cell lines and tissues and have obtained a comprehensive picture of cholesterol and cholesteryl esters content in them. Specifically, among cholesteryl esters, we found that mammalian cells and tissues largely possess monounsaturated and polyunsaturated variants. Taken together, our lipidomics compatible LC-MS method to study this lipid class opens new avenues in understanding systemic and tissue-level cholesterol metabolism under various physiological conditions.

In today’s rapidly evolving scientific landscape, publishing groundbreaking research is just the first step. Ensuring that your work gains the visibility it deserves is crucial for advancing your career and the field of metabolomics as a whole. This lecture will explore innovative strategies for marketing your research effectively, focusing on increasing citations and enhancing your academic footprint. We will delve into the power of content marketing, digital platforms, and strategic dissemination, providing a roadmap to elevate your research from the bench to a global audience. Attendees will leave with actionable insights to amplify their research impact and a deeper understanding of how modern marketing techniques can catalyze scientific success.

Representation is vital in advancing equity and innovation across scientific fields. South Asians in Mass Spectrometry (SAMS) is a community-driven initiative that champions diversity within mass spectrometry by empowering South Asian professionals and fostering inclusion. SAMS aims to create an inclusive network where South Asian scientists can connect, collaborate, and contribute to the field’s evolution. Through mentorship, networking opportunities, and a commitment to promoting diverse perspectives, SAMS is dedicated to shaping a more representative scientific community. By highlighting the talent and contributions of South Asians in mass spectrometry, SAMS inspires the next generation of scientists and drives forward-thinking research.