From the point of view of patient care, your recent debate over classical genetics123 makes it clear that any form of current classical one-by-one gene status assessment will not be adequately informative to assess an actual patient's genetic risks.

Before there were tests to identify specific genetic mutations, cancer geneticists relied primarily on cancer family pedigrees, and interrelated family pedigrees, to suggest the cancer-risk status of an individual. These interconnected family cancer pedigrees were in effect a dynamic system-wide read-out of the outcome cancer-risk status of that individual, accommodating the actual vast variability and uncertainty inherent in the genetic expression as Goodman et al. have outlined.2 Remarkably this old corpus of interconnected family pedigree information may be just the "new" data form we seek to address the recognized enormous complexity, if not molecular uncertainty, in an individual's genetic profile.

We have demonstrated that one can apply a normative-model-driven...

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