Hunter Gaudio - Dr. Elemento, Dr. Cristofanilli - Summer Immersion Term, Week 4

This was another productive week focused on liquid biopsy research and clinical implementation. On Monday, the Circulating Tumor Cell (CTC) lab team met with members from the Institute of Computational Biology (ICB) to discuss an analysis plan for the whole exome sequencing (WES) dataset we are receiving from Natera. This data was generated from the primary tumors of patients who underwent circulating tumor DNA testing using the Signatera platform. We learned that the ICB already has a pipeline built that uses and cross-checks several methods for variant identification. Running the data through this pipeline should provide us with a comprehensive mutational profile of each patient's tumor, that we will then be able to evaluate, contextualized with clinical information. The initial goal of this analysis will be to characterize the performance of Signatera's liquid biopsy test across different mutational profiles. In the afternoon we had Dr. Cristofanilli's lab meeting where we discussed all of the different projects that will have abstracts submitted to the San Antonio Breast Cancer Symposium. 

On Tuesday, we attended a lecture by Dr. Mert Sabuncu on his lab's work building computational platforms for the analysis of medical images. He discussed compress sensing, which enables missing measurements to be inferred via computation. He also spoke about "time order" projects which involves training a model to temporally order a set of images, and then analyzing the features with the greatest importances to determine "irreversible change". This could be the processes of aging or the degenerative behavior of certain diseases. Lastly, he spoke about a project that focuses on the value of longitudinal data from mammograms. He explained that the temporal dynamics of these images may be able to identify small lesion growth over time that radiologists could miss by just evaluating a single image. After the lecture I shadowed Dr. Cristofanilli and Dr. Gianni in the outpatient breast cancer clinic. 

The rest of the week I spent learning how to use different WES analysis and data visualization packages (Mutect2 and maftools for R) and reviewing literature on CTC clusters. I will be joining a project that is looking to quantify the amount of these clusters, which are not detected by current clinically approved CTC detection platforms. It is believed that these cells are mesenchymal cells, grouped together, with larger potential to initiate metastasis. If they are mesenchymal in nature, they would not express the cell-surface markers typically targeted by current liquid biopsy platforms that are utilized to identify the presence of cancer in the blood. The goal is to eventually develop a machine learning model that incorporates clinical data, liquid biopsy data generated via commercially available platforms, and CTC clusters data generated within the CTC lab to predict local and regional recurrence. 

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