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Biology subjects

Khanna, V.

Publications and source records attributed to Khanna, V..

3 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↗

Chromosomal position of ribosomal protein genes impacts long term evolution of Vibrio cholerae.

It is unclear how gene order within the chromosome influences bacterial evolution. The genomic location of genes encoding the flow of genetic information is biased towards the replication origin (oriC) in fast-growing bacteria. To study the role of chromosomal location on cell physiology we relocated the S10-spec- locus (S10), harboring half of ribosomal protein genes, to different chromosomal positions in the fast-growing pathogen V. cholerae. We found that growth rate, fitness and infectivity inversely correlated the distance between S10 and oriC. To gain insight into the evolutionary effect of ribosomal protein genomic position, we evolved strains bearing S10 at its current oriC-proximal location or derivatives where the locus far from it, at the chromosomal termini. All populations increased their growth rate along the experiment regardless S10 genomic location. However, the growth rate advantage of an oriC-proximal location persisted along experimental evolution indicating that suppressor mutations cannot compensate S10 genomic position. An increment in biofilm forming capacity was another common trait observed along the experiment. Deep sequencing of populations showed on average 1 mutation fixed each 100 generations, mainly at genes linked to flagellum biosynthesis regulation, lipopolysaccharide synthesis, chemotaxis, biofilm and quorum sensing. We selected fast-growing clones displaying a [~]10% growth rate increment. We found that they harbored inactivating mutations at, among other sites, the flagellum master regulators flrAB. The introduction of these mutations into naive V. cholerae strains resulted in a [~]10% increase of growth rate. Our study therefore demonstrates that the location of ribosomal protein genes conditions the evolutionary trajectory of growth rate in the long term. While genomic content is highly plastic in prokaryotes, gene order is an underestimated factor that conditions cellular physiology and lineage evolution. The lack of suppression enables artificial gene relocation for genetic circuit reprogramming.

microbiology↗

A SKI subcomplex specifically required for the degradation of ribosome-free RNA regions

The Ski2-Ski3-Ski8 (SKI) complex assists the RNA exosome during the 3-5 degradation of cytoplasmic transcripts. Previous reports showed that the SKI complex is involved in the 3-5 degradation of mRNA, including 3 untranslated regions (UTRs), devoid of ribosomes. Paradoxically, we recently showed that the SKI complex directly interacts with ribosomes during the co-translational mRNA decay and that this interaction is necessary for its RNA degradation promoting activity. Here, we characterized a new SKI-associated factor, Ska1, which antagonizes the SKI-ribosome interaction. We showed that the SKI-Ska1-subcomplex is specifically involved in the degradation of ribosome-free RNA regions such as long mRNA 3UTRs and cytoplasmic lncRNAs. We propose a model in which the SKI-exosome complex first targets ribosome-free RNA 3ends in its Ska1-associated form. When the complex reaches the mRNA coding sequence, the Ska1-SKI-exosome complex is exchanged for the SKI-exosome, which interacts directly with ribosomes in order to resume the degradation process.

molecular biology↗