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Rabbani, N.

Publications and source records attributed to Rabbani, N..

2 recordsLinked to original sources

A synthetic MALDI-TOF MS atlas for microbial classification across hospitals

Matrix-Assisted Laser Desorption/Ionization Time-of-Flight (MALDI-TOF) mass spectrometry (MS) is central to routine clinical microbiology for species identification. Its combination with machine learning is constrained by fragmented public datasets, species imbalance and acquisition-related variability. Synthetic datasets could provide more training data, but they must preserve the spectral information needed to make predictions on real samples. Here, we present an open, synthetic MALDI-TOF MS atlas comprising 4.3 million spectra across 43 clinically relevant bacterial species. To construct the atlas, we harmonised public repositories from three countries and trained a species- and institution-conditioned concept-bottleneck generative variational autoencoder (CBGM-VAE) on 179,086 measured spectra. We assessed the atlas as both a stand-alone training resource and a complement to real data, using bacterial species classification as a functional benchmark. Evaluation comprised 7,269 real spectra from more than 7 countries, 24 institutions and multiple acquisition platforms, covering: temporal, technical, biological and combined shifts. A neural network trained only on synthetic spectra achieved F1 scores ranging from 0.788 to 1.000 across external cohorts. When synthetic spectra were combined with real training data, classification performance improved or matched using real data only. These findings demonstrate that the atlas retains transferable information and can complement measured data. The openly released atlas provides a reusable resource for supervised learning and benchmarking. It can also be explored for pretraining representation-learning and foundation models in MALDI-TOF MS research.

microbiology↗

Vulnerabilities of the SARS-CoV-2 virus to proteotoxicity -- opportunity for repurposed chemotherapy of COVID-19 infection

The global pandemic of COVID-19 disease caused by infection with the SARS-CoV-2 coronavirus, has produced an urgent requirement and search for improved treatments whilst effective vaccines are developed. A strategy for improved drug therapy is to increase levels of endogenous reactive metabolites for selective toxicity to SARS-CoV-2 by preferential damage to the viral proteome. Key reactive metabolites producing major quantitative damage to the proteome in physiological systems are: reactive oxygen species (ROS) and the reactive glycating agent methylglyoxal (MG); cysteine residues and arginine residues are their most susceptible targets, respectively. From sequenced-based prediction of the SARS-CoV-2 proteome, we found 0.8-fold enrichment or depletion of cysteine residues in functional domains of the viral proteome; whereas there was a 4.6-fold enrichment of arginine residues, suggesting SARS-CoV-2 is resistant to oxidative agents and sensitive to MG. For arginine residues of the SARS-CoV-2 predicted to be in functional domains, we examined which are activated towards modification by MG - residues with predicted or expected low pKa by neighbouring group in interactions. We found 25 such arginine residues, including 2 in the spike protein and 10 in the nucleoprotein. These sites were partially conserved in related coronaviridae: SARS-COV and MERS. Finally, we identified drugs which increase cellular MG concentration to virucidal levels: antitumor drugs with historical antiviral activity, doxorubicin and paclitaxel. Our findings provide evidence of potential vulnerability of SARS-CoV-2 to inactivation by MG and a scientific rationale for repurposing of doxorubicin and paclitaxel for treatment of COVID-19 disease, providing efficacy and adequate therapeutic index may be established.

biochemistry↗