Clonality inference in multiple tumor samples using phylogeny
Computer applications in the biosciences : CABIOS
Intra-tumor heterogeneity presents itself through the evolution of subclones during cancer progression. While recent research suggests that this clonal diversity is a key factor in therapeutic failure, the determination of subclonal architecture of human tumors remains a challenge. To address the problem of accurately determining subclonal frequencies in tumors as well as their evolutionary history, we have developed a novel combinatorial method named CITUP (Clonality Inference in Tumors Using
... hylogeny). An important feature of CITUP is its ability to exploit data from multiple time-point and/or regional samples from a single patient in order to improve estimates of mutational profiles and subclonal frequencies. Using extensive simulations and real datasets comprising tumor samples from two leukemia drugresponse studies, we show that CITUP can infer the evolutionary trajectory of human tumors with high accuracy. keywords: Cancer progression, intra-tumor heterogeneity, combinatorial methods iv To my beloved parents Faiz and Sadeta, and my dear sister Faiza v You can't connect the dots looking forward; you can only connect them looking backwards. So you have to trust that the dots will somehow connect in your future. You have to trust in something: your gut, destiny, life, karma, whatever. This approach has never let me down, and it has made all the difference in my life.