Throughout the preceding century, two principles have been used to quantify synergy of drug combinations: the Dose Equivalence Principle (DEP), introduced by Loewe 1, 2, and the Multiplicative Survival Principle (MSP), introduced by Bliss 3. Thus the proposed formalism can provide a consistent, unbiased interpretation of drug synergy, and accelerate the translatability of synergy studies. We show how these biases systematically impact synergy classification in large combination screens, potentially misleading discovery efforts. Specifically, we describe how traditional metrics mask consequential synergistic interactions, and contain biases dependent on the Hill-slope and maximal effect of single-drugs. From this, we show how biases emerge due to intrinsic assumptions which hinder their broad applicability and impact the interpretation of synergy in discovery efforts. With this formalism, we clarify the relationship between the dominant drug synergy principles, and present a mapping of commonly used frameworks onto a unified synergy landscape. Here we present a mass-action based formalism to quantify synergy. The fragmented state of the field confounds analysis, impedes reproducibility, and delays clinical translation of potential combination treatments. ĭrug combination discovery depends on reliable synergy metrics but no consensus exists on the correct synergy criterion to characterize combined interactions. The code for the interactive Jupyter notebook demonstration of MuS圜 is available at. A web application to calculate MuS圜 parameters is available at. Īll code required for recreating manuscript analyses from the MuS圜 fits are available for review in the repository. The synergy datasets generated in this study are available in a repository at. Clinical trial data was collected from the Drug Combination Database (DCDB) (10.1093/database/bau124,, Figs. The datasets analyzed in this study were obtained from publicly available sources with DOIs Mott (10.1038/srep13891, Figs. Schreeder hopes that MAT can save lives and prevent certain emergencies altogether.GUID: 3F92AD8E-B9FA-4523-9AE3-5F50216D4A83 Data Availability Statement By responding to the crises of treatment-resistant depression, substance use disorders and addiction, chronic pain, and PTSD, Dr. Later, after moving to Huntsville with his wife Caroline, he wanted to respond to the opioid overdose and suicide crisis in a preventative way and continued education and certifications in medication-assisted therapy or MAT. Schreeder worked in the field of Urgent Care. Schreeder continues to practice Emergency Medicine, but he began practicing in urgent and non-emergent outpatient clinic services over the years. He completed his medical training and residency in Emergency Medicine at Louisiana State University School of Medicine in Shreveport, Louisiana.ĭr. Upon graduation, he continued his studies at the University of Alabama School of Medicine. In 2006, he graduated from Washington and Lee University with a Bachelor of Science in Chemistry – Engineering. Schreeder, a native of Huntsville, AL, is a board-certified Emergency Medicine physician. Chang enjoys physical fitness, watching football, and spending time with family in his spare time.ĭr. Chang also serves as a team physician for the Houston Texans. Chang also brought his business expertise to the practice of medicine, as he was instrumental in the start-up and management of several free-standing ERs in Texas. His clinical interests also include wellness and addiction medicine, which stems from his passion for helping others live healthier and happier lives. Chang brings more than 20 years of experience managing and treating sick patients, from sports injuries to heart attacks. Trained and boarded in Emergency Medicine, Dr. Chang completed his General Surgery internship at the University of Texas in Houston, and in 2000, he completed an Emergency Medicine residency at Vanderbilt University. He received his Bachelors of Science at Stanford University, then went on to the University of California San Francisco School of Medicine, where he obtained his Doctorate of Medicine in 1996. Michael Chang is a native of Houston, TX.
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