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Alex Aravanis is a leader in research and development of technologies and clinical tests utilizing the latest tools in DNA analysis and data science. In this episode, Alex delves into two interconnected topics: liquid biopsies and epigenetics. He begins by tracing the trajectory of genome sequencing and tumor sequencing, setting the stage for a detailed exploration of liquid biopsies as an early cancer detection method. The discussion encompasses key concepts such as cell-free DNA, DNA methylation, sensitivity, specificity, and the predictive values associated with liquid biopsies. Transitioning to epigenetics, Alex examines the intricate interplay of DNA methylation and aging biology and explores the possibility of using cellular reprogramming to reverse epigenetic changes that occur with aging.

We discuss:

• Alex’s background in applying engineering to problems in medicine [3:15];
• A primer on human genetics, and the history and current landscape of DNA sequencing [11:00];
• The advent and evolution of liquid biopsies for early detection of cancer [23:15];
• The role of cell-free DNA in cancer detection: how incidental findings in non-invasive prenatal testing led to the development of liquid biopsies [40:15];
• The development of a universal blood test for cancer detection and a discussion of specificity of tests [46:00];
• Advancements in cell-free DNA analysis and development of a multi-cancer screening test at GRAIL [51:00];
• DNA methylation explained [58:15];
• Optimizing cancer detection with methylation analysis of cfDNA in small blood samples [1:02:45];
• The importance of understanding sensitivity, specificity, positive predictive value, and negative predictive value in cancer screening [1:08:00];
• The performance of the GRAIL Galleri test and its ability to detect various types and stages of cancer [1:21:00];
• Do early cancer detection methods, like liquid biopsies, translate to improvement in overall survival? [1:27:45];
• The role of epigenetics in aging [1:39:30];
• How cell-free DNA methylation patterns can help identify a cancer’s tissue of origin [1:45:30];
• Cellular and epigenetic reprogramming and other exciting work in the field of aging [1:52:30]; and
• More.

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