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Biology subjects

Agar, N.

Publications and source records attributed to Agar, N..

2 recordsLinked to original sources

Deep Learning on Multimodal Chemical and Whole Slide Imaging Data for Predicting Prostate Cancer Directly from Tissue Images

Prostate cancer is one of the most common cancers globally and is the second most common cancer in the male population in the US. Here we develop a study based on correlating the H&E-stained biopsy data with MALDI mass-spectrometric imaging of the corresponding tissue to determine the cancerous regions and their unique chemical signatures, and variation of the predicted regions with original pathological annotations. We spatially register features obtained through deep learning from high-resolution optical micrographs of whole slide H&E stained data with MSI data to correlate the chemical signature with the tissue anatomy of the data, and then use the learned correlation to predict prostate cancer from observed H&E images using trained co-registered MSI data. We found that this system is more robust than predicting from a single imaging modality and can predict cancerous regions with[~] 80% accuracy. Two chemical biomarkers were also found to be predicting the ground truth cancerous regions. This will improve on generating patient treatment trajectories by more accurately predicting prostate cancer directly from H&E-stained biopsy images.

cancer biology↗

A druggable addiction to de novo pyrimidine biosynthesis in diffuse midline glioma

Diffuse midline glioma (DMG) is a uniformly fatal pediatric cancer driven by oncohistones that do not readily lend themselves to drug development. To identify druggable targets for DMG, we conducted a genome-wide CRISPR screen that reveals a DMG selective dependency on the de novo pathway for pyrimidine biosynthesis. This metabolic vulnerability reflects an elevated rate of uridine/uracil degradation that depletes DMG cells of substrates for the alternate salvage pathway for pyrimidine biosynthesis. A clinical stage inhibitor of DHODH (rate limiting enzyme in the de novo pathway) diminishes UMP pools, generates DNA damage, and induces apoptosis through suppression of replication forks--an "on target" effect, as shown by uridine rescue. MALDI mass spectroscopy imaging demonstrates that this DHODH inhibitor (BAY2402234) accumulates in brain at therapeutically relevant concentrations, suppresses de novo pyrimidine biosynthesis in vivo, and prolongs survival of mice bearing intracranial DMG xenografts, highlighting BAY2402234 as a promising therapy against DMGs.

cancer biology↗