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Biology subjects

Khandekar, N.

Publications and source records attributed to Khandekar, N..

2 recordsLinked to original sources

NoisyFlow: Differentially Private Optimal Transport Using Neural Networks for Secure Biomedical Data Sharing

MotivationAdvancing data sharing in biomedical research, particularly for sensitive genomic and clinical datasets, is crucial for improving model performance across diverse patient populations. However, stringent privacy concerns hinder collaboration and limit insights derived from multi-institutional datasets. Current approaches to privacy-preserving data sharing fail to address gaps between data distributions. ResultsWe introduce NoisyFlow, a differentially private neural network-based optimal transport framework designed to enable secure and unbiased biomedical data sharing. By integrating optimal transport theory with neural networks and differential privacy mechanisms, our framework aligns data distributions across institutions while preserving individual privacy. NoisyFlow eliminates the need for direct data sharing and reduces distribution shifts caused by covariate and batch effects. Empirical evaluations demonstrate the frameworks effectiveness in handling high-dimensional single-cell genomic data and histopathology images, achieving superior privacy guarantees while maintaining high utility in downstream tasks such as disease classification. Availability and implementationThe implementation of NoisyFlow is available at https://github.com/liyy2/NoisyFlow. Contactmark@gersteinlab.org. Supplementary informationSupplementary data are available online.

bioinformatics↗

Structural characterization of antibody-responses from Zolgensma treatment provides the blueprint for the engineering of an AAV capsid suitable for redosing

Monoclonal antibodies (mAbs) are useful tools to dissect the neutralizing antibody response against the adeno-associated virus (AAV) capsids used as gene therapy delivery vectors. This study structurally characterizes the interactions of 21 human-derived antibodies from patients treated with the AAV9 vector, Zolgensma(R), utilizing high-resolution cryo-electron microscopy. The majority of the bound antibodies do not conform to the icosahedral symmetry of the capsid, thus requiring localized reconstructions. These complex structures provide unprecedented details of the mAbs binding interfaces, with some antibodies inducing structural perturbations of the capsid upon binding. Key surface capsid amino acid residues were identified facilitating the design of capsid variants with an antibody escape phenotype, with the potential to expand the patient cohort treatable with AAV9 vectors to include those that were previously excluded due to their pre-existing neutralizing antibodies, and possibly also to those requiring redosing.

immunology↗