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Topics expected to influence personalized medicine (PM), where medical decisions, practices, and treatments are tailored to the individual patient, are reviewed. Lack of discrimination due to different biological conditions that express similar values of numerical variables (ambiguity) is regarded to be a major potential barrier for PM. This material explores possible causes and sources of ambiguity and offers suggestions for mitigating the impacts of uncertainties. Three causes of ambiguity are identified: (1) delayed adoption of innovations, (2) inadequate emphases, and (3) inadequate processes used when new medical practices are developed and validated. One example of the first problem is the relative lack of medical research on "compositional data" -the type that characterizes leukocyte data. This omission results in erroneous use of data abundantly utilized in medicine, such as the blood cell differential. Emphasis on data output ‒not biomedical interpretation that facilitates the use of clinical data‒ exemplifies the second type of problems. Reliance on tools generated in other fields (but not validated within biomedical contexts) describes the last limitation. Because reductionism is associated with these problems, non-reductionist alternatives are reviewed as potential remedies. Data structuring (converting data into information) is considered a key element that may promote PM. To illustrate a process that includes data-information-knowledge and decision-making, previously published data on COVID-19 are utilized. It is suggested that ambiguity may be prevented or ameliorated. Provided that validations are grounded on biomedical knowledge, approaches that describe certain criteria - such as non-overlapping data intervals of patients that experience different outcomes, immunologically interpretable data, and distinct graphic patterns - can inform, at personalized bases, earlier and/or with fewer observations., (Copyright © 2022 The Authors. Published by Elsevier Ltd.. All rights reserved.)