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Sebastian, K. R.

Publications and source records attributed to Sebastian, K. R..

2 recordsLinked to original sources

Deep learning on reflectance confocal microscopy improves Raman spectral diagnosis of basal cell carcinoma

SignificanceRaman spectroscopy may be useful to assist Mohs micrographic surgery for skin cancer diagnosis; however, the specificity of Raman spectroscopy is limited by the high spectral similarity between tumors and normal tissues structures such as epidermis and hair follicles. Reflectance confocal microscopy (RCM) can provide imaging guidance with morphological and cytological details similar to histology. Combining Raman spectroscopy with deep-learning-aided RCM has the potential to improve the diagnostic accuracy of Raman without requiring additional input from the clinician. AimWe seek to improve the specificity of Raman for basal cell carcinoma (BCC) by integrating information from RCM images using an Artificial Neural Network. ApproachA Raman biophysical model was used in prior work to classify BCC tumors from surrounding normal tissue structures. 191 RCM images were collected from the same site as the Raman data and served as inputs to train two ResNet50 networks. The networks selected the hair structure images and epidermis images respectively within all the images corresponding to the positive predictions of the Raman Biophysical Model. ResultsDeep learning on RCM images removes 54% of false positive predictions from the Raman Biophysical Model result and keeps the sensitivity as 100%. The specificity was improved from 84.8% by using Raman spectra alone to 93.0% by integrating Raman spectra with RCM images ConclusionsCombining Raman spectroscopy with deep-learning-aided RCM imaging is a promising tool to guide tumor resection surgery.

bioengineering↗

High-Throughput and High-Dimensional Single Cell Analysis of Antigen-Specific CD8+ T cells

Although critical to T cell function, antigen specificity is often omitted in high-throughput multi-omics based T cell profiling due to technical challenges. We describe a high-dimensional, tetramer-associated T cell receptor sequencing (TetTCR-SeqHD) method to simultaneously profile TCR sequences, cognate antigen specificities, targeted gene-expression, and surface-protein expression from tens of thousands of single cells. Using polyclonal CD8+ T cells with known antigen specificity and TCR sequences, we demonstrated over 98% precision for detecting the correct antigen specificity. We also evaluated gene-expression and phenotypic differences among antigen-specific CD8+ T cells and characterized phenotype signatures of influenza- and EBV-specific CD8+ T cells that are unique to their pathogen targets. Moreover, with the high-throughput capacity of profiling hundreds of antigens simultaneously, we applied TetTCR-SeqHD to identify antigens that preferentially enrich cognate CD8+ T cells in type 1 diabetes patients compared to healthy controls, and discovered a TCR that cross reacts between diabetic and microbiome antigens. TetTCR-SeqHD is a powerful approach for profiling T cell responses.

immunology↗