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Anand Anbarasu

Publications and source records attributed to Anand Anbarasu.

7 recordsLinked to original sources

Multimodal artificial intelligence and machine learning in oncology: from data integration to precision cancer care.

Cancer remains a major global health burden, with approximately 20 million new cases and 9.7 million cancer-related deaths reported globally in 2022. While advances in radiological imaging, molecular profiling, and clinical data have enhanced the interpretation of disease progression, the availability of multiple such modalities still does not meet the needs of a large patient population. This narrative review focuses on the role of multimodal artificial intelligence and machine learning in bridging the gap in interpreting heterogeneous modalities to improve risk prediction, prognostic assessment, and treatment decision-making in precision oncology. Multimodal frameworks such as Pathomic Fusion illustrate how complementary histopathological and genomic information can be integrated for cancer diagnosis and prognostic modeling. Multimodal models have demonstrated potential in virtual biopsy, cancer screening, prognostic prediction, radiotherapy planning, intraoperative guidance, and clinical-trial design using digital twins and synthetic control arms. The major limitations of incorporating multimodal artificial intelligence and machine learning in oncology include data heterogeneity, demographic or institutional biases, and reproducibility challenges that hinder translation. Accordingly, appropriate data-governance strategies, fairness audits, and privacy-preserving approaches such as federated learning should be considered where appropriate. Future progress will depend on the development of standardized benchmarking datasets, robust external validation, seamless integration with electronic health records and picture archiving and communication systems, and the implementation of explainable, secure, and clinically validated multimodal artificial intelligence frameworks that support precision oncology in routine clinical practice.

deep learning↗

Genomic and structural analysis of dacB variants associated with cephalosporin resistance in Pseudomonas aeruginosa.

The rise of resistance to fourth-generation cephalosporin in Pseudomonas aeruginosa (P. aeruginosa) is a global concern. The resistance is largely driven by variants of chromosomally encoded AmpC β-lactamase, known as Pseudomonas-derived cephalosporinase (PDC), which arise from the mutations in the ampC gene. In addition, alteration in dacB, which encode the penicillin-binding protein 4 (PBP4), can lead to the overexpression of ampC, thereby contributing to β-lactam resistance. Present work analyzed 208 clinical isolates of P. aeruginosa using whole-genome sequencing (WGS) and detected multiple nonsynonymous single nucleotide polymorphisms (nsSNPs), such as Y264C, G444D, and a double mutation (A394P-T428P). All nsSNPs were predicted to be deleterious by several prediction program. Molecular dynamics (MD) simulations suggested that these substitutions destabilize PBP4, increase structural flexibility, and contribute to the resistance mechanism, which favored their selection. To determine the effective therapeutics against these mutations, molecular docking was conducted with various antibiotics. Cefoperazone exhibited the highest binding affinity (-7.3 kcal/mol) among multiple PBP4 variants. The Molecular dynamics (MD) simulations and Molecular Mechanics Poisson Boltzmann Surface Area calculations (MMPBSA) further confirmed the favorable interactions between cefoperazone and PBP4 variants. In vitro MIC analyses supported these findings, indicating that cefoperazone displayed significant activity against clinical dacB mutants of P. aeruginosa. The study offers structural insight of dacB variants leading to antibiotic resistance and emphasizes the need to prioritize specific antibiotics to address the challenges arising from protein mutations.

Pseudomonas aeruginosa↗

Influence of cation-pi interactions on RNA-binding proteins.

The energy contribution due to cation-pi interactions has been computed for 37 RNA binding proteins. The contribution of these cation-pi interacting residues in sequential separation, secondary structure involvement, solvent accessibility, and stabilization centers has been evaluated. Sequential separation of the cation-pi involving residues show that, long range contacts predominates in all the proteins studied. Lys and Arg prefers to be in helical structures. Of the cation-pi interacting residues, Arg and Lys were in the exposed regions and the aromatic residues (Phe, Tyr and Trp) were in the buried and partially buried regions in the protein structures. Stabilization centers for these proteins showed that all the five residues found in cation-pi interactions are important in locating one or more of such centers. On the whole, the results presented in this work will be very useful for further investigations on the specificity and selectivity of RNA binding proteins and also for their structural studies.

Amino Acids, Aromatic↗

Computation of non-covalent interactions in TNF proteins and interleukins.

The roles played by the non-covalent interactions have been investigated for a set of six TNF proteins and nine Interleukins. The stabilizing residues have been identified by a consensus approach using the concepts of available surface area, medium and long-range interactions and conservation of amino acid residues. The cation-pi interactions have been computed based on a geometric approach such as distance and energy criteria. We identified an average of 1 energetically significant cation-pi interactions in every 94 residues in TNF proteins and 1 in every 62 residues in Interleukins. In TNF proteins, the cationic groups Lys preferred to be in helix while Arg preferred to be in strand regions while in Interleukins the Arg residues preferred to be in helix and Lys preferred to be in strand regions. From the available surface area calculations, we found that, almost all the cation and pi residues in TNF proteins and Interleukins were either in buried or partially buried regions and none of them in the exposed regions. Medium and long-range interactions were predominant in both TNF proteins and Interleukins. It was observed that the percentage of stabilizing centers were more in TNF proteins as compared to the Interleukins, while the percentage of conserved residues were more in Interleukins than in TNF proteins. In the stabilizing residues Lys was observed to be a stabilizing residue in both TNF proteins and Interleukins. Among the aromatic group, Phe was seen to be a stabilizing residue in both TNF and Interleukins. We suggest that this study on the computation of cation-pi interactions in TNF proteins and Interleukins would be very helpful in further understanding the structure, stability and functional similarity of these proteins.

Algorithms↗

Septicaemic melioidosis in a tertiary care hospital in south India.

BACKGROUND & OBJECTIVES: Melioidosis and the causative organism Burkholderia pseudomallei are being recognized gradually in various centres in India. In the septicaemic form, melioidosis is a serious and life threatening condition which requires early detection and specific treatment to avoid case fatality. A review of patients with septicaemic melioidosis at a tertiary care hospital in south India was carried out with a view to define the clinical features, predisposing conditions, if any, and the outcome. METHODS: A total of 28 patients with culture proven septicaemic melioidosis during December 1993 to December 2002 were included. Information on clinical details and outcome was obtained and antibiotic susceptibility of the isolates studied. RESULTS: Of the 28 patients of blood culture proven septicaemic melioidosis, the organism was also isolated from pus in two patients. The presenting clinical features were varied, most presenting as pyrexia of unknown origin or visceral abscesses, or septic arthiritis. Associated/predisposing conditions were present in 50 per cent of the patients, and diabetes mellitus was the commonest one. mortality was 58 per cent in our series. INTERPRETATION & CONCLUSION: Melioidosis is an emerging infection in India. The magnitude of the problem can only be assessed by increasing awareness, both of its existence in the clinical setting and its identification in the laboratory.

Adolescent↗

Indirect immunofluorescent antibody test for the rapid diagnosis of melioidosis.

Culture is the only reliable method available at present for the diagnosis of melioidosis. Though serological tests have been described, their value in routine diagnosis is controversial. All indirect immunofluorescent assay (IFA) was therefore evaluated to determine its use in the diagnosis of melioidosis. Whole cell antigen prepared from a laboratory isolate of Burkholderia pseudomallei was used to assay IgG and IgM antibodies. Fourteen of the 22 (63.6%) culture proven cases had IgM antibodies while only 10 (45.5%) had IgG antibodies. Negative predictive value of IgM assay was 92 per cent. Positive predictive value was 100 per cent if both IgM and IgG were considered together. The present study done on a limited number of samples suggests that IFA may be useful in routine diagnosis of melioidosis.

Antibodies, Bacterial↗