bioRxiv ScienceSearch

Biology subjects

Bhargava, R.

Publications and source records attributed to Bhargava, R..

2 recordsLinked to original sources

A Fully Automated, Faster Noise Reduction Approach to Increasing the Analytical Capability of Chemical Imaging for Digital Histopathology

High dimensional data, for example from infrared spectral imaging, involves an inherent trade-off in the acquisition time and quality of spatial-spectral data. Minimum Noise Fraction (MNF) developed by Green et al. [1] has been extensively studied as an algorithm for noise removal in HSI (Hyper-Spectral Imaging) data. However, there is a speed-accuracy trade-off in the process of manually deciding the relevant bands in the MNF space, which by current methods could become a person month time for analyzing an entire TMA (Tissue Micro Array). We propose three approaches termed Fast MNF, Approx MNF and Rand MNF where the computational time of the algorithm is reduced, as well as the entire process of band selection is fully automated. This automated approach is shown to perform at the same level of reconstruction accuracy as MNF with large speedup factors, resulting in the same task to be accomplished in hours. The different approximations of the algorithm, show the reconstruction accuracy vs storage (50x) and runtime speed (60x) trade-off. We apply the approach for automating the denoising of different tissue histology samples, in which the accuracy of classification (differentiating between the different histologic and pathologic classes) strongly depends on the SNR (signal to noise ratio) of recovered data. Therefore, we also compare the effect of the proposed denoising algorithms on classification accuracy. Since denoising HSI data is done without any ground truth, we also use a metric that assesses the quality of denoising in the image domain between the noisy and denoised image in absence of ground truth.

bioinformatics

Exome-Capture RNA-Sequencing Of Decade-Old Breast Cancers And Matched Decalcified Bone Metastases Identifies Clinically Actionable Targets

Bone metastases (BoM) are a significant cause of morbidity in patients with Estrogen-receptor (ER)-positive breast cancer, yet characterizations of human specimens are limited. In this study, exome-capture RNA-sequencing (ecRNA-seq) on aged (8-12 years), formalin-fixed paraffin-embedded (FFPE) and decalcified cancer specimens was first evaluated. Gene expression values and RNA-seq quality metrics from FFPE or decalcified tumor RNA showed minimal differences when compared to matched flash-frozen or non-decalcified tumors. ecRNA-seq was then applied on a longitudinal collection of 11 primary breast cancers and patient-matched de novo or recurrent BoM. BoMs harbored shifts to more Her2 and LumB PAM50 intrinsic subtypes, temporally influenced expression evolution, recurrently dysregulated prognostic gene sets and altered expression of clinically actionable genes, particularly in the CDK-Rb-E2F and FGFR-signaling pathways. Taken together, this study demonstrates the use of ecRNA-seq on decade-old and decalcified specimens and defines expression-based tumor evolution in long-term, estrogen-deprived metastases that may have immediate clinical implications.\n\nGrant SupportResearch funding for this project was provided in part by a Susan G. Komen Scholar award to AVL and to SO, the Breast Cancer Research Foundation (AVL and SO), the Fashion Footwear Association of New York, the Magee-Womens Research Institute and Foundation, and through a Postdoctoral Fellowship awarded to RJW from the Department of Defense (BC123242). NP was supported by a training grant from the NIH/NIGMS (2T32GM008424-21) and an individual fellowship from the NIH/NCI (5F30CA203095).\n\nConflicts of Interest DisclosureNo relevant conflicts of interest disclosed for this study.\n\nAuthor ContributionsStudy concept and design (NP, RJW, SO, AVL); acquisition, analysis, or interpretation of data (all authors); drafting of the manuscript (NP, RJW, SO, AVL); critical revision of the manuscript for important intellectual content (all authors); administrative, technical, or material support (PCL, AB, RB, KRW, WH, JK, MR, ZF, AMB).

cancer biology