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Raúl Rabadán

Publications and source records attributed to Raúl Rabadán.

3 recordsLinked to original sources

Quantifying Genetic Innovation: Mathematical Foundations for the Topological Study of Reticulate Evolution

A topological approach to the study of genetic recombination, based on persistent homology, was introduced by Chan, Carlsson, and Rabadán in 2013. This associates a sequence of signatures called barcodes to genomic data sampled from an evolutionary history. In this paper, we develop theoretical foundations for this approach. First, we present a novel formulation of the underlying inference problem. Specifically, we introduce and study the novelty profile, a simple, stable statistic of an evolutionary history which not only counts recombination events but also quantifies how recombination creates genetic diversity. We propose that the (hitherto implicit) goal of the topological approach to recombination is the estimation of novelty profiles. We then study the problem of obtaining a lower bound on the novelty profile using barcodes. We focus on a low-recombination regime, where the evolutionary history can be described by a directed acyclic graph called a galled tree, which differs from a tree only by isolated topological defects. We show that in this regime, under a complete sampling assumption, the $1^\mathrm{st}$ barcode yields a lower bound on the novelty profile, and hence on the number of recombination events. For $i>1$, the $i^{\mathrm{th}}$ barcode is empty. In addition, we use a stability principle to strengthen these results to ones which hold for any subsample of an arbitrary evolutionary history. To establish these results, we describe the topology of the Vietoris--Rips filtrations arising from evolutionary histories indexed by galled trees. As a step towards a probabilistic theory, we also show that for a random history indexed by a fixed galled tree and satisfying biologically reasonable conditions, the intervals of the $1^{\mathrm{st}}$ barcode are independent random variables. Using simulations, we explore the sensitivity of these intervals to recombination.

math.AT↗

Predicting Clinical Outcomes in Glioblastoma: An Application of Topological and Functional Data Analysis

Glioblastoma multiforme (GBM) is an aggressive form of human brain cancer that is under active study in the field of cancer biology. Its rapid progression and the relative time cost of obtaining molecular data make other readily-available forms of data, such as images, an important resource for actionable measures in patients. Our goal is to utilize information given by medical images taken from GBM patients in statistical settings. To do this, we design a novel statistic---the smooth Euler characteristic transform (SECT)---that quantifies magnetic resonance images (MRIs) of tumors. Due to its well-defined inner product structure, the SECT can be used in a wider range of functional and nonparametric modeling approaches than other previously proposed topological summary statistics. When applied to a cohort of GBM patients, we find that the SECT is a better predictor of clinical outcomes than both existing tumor shape quantifications and common molecular assays. Specifically, we demonstrate that SECT features alone explain more of the variance in GBM patient survival than gene expression, volumetric features, and morphometric features. The main takeaways from our findings are thus twofold. First, they suggest that images contain valuable information that can play an important role in clinical prognosis and other medical decisions. Second, they show that the SECT is a viable tool for the broader study of medical imaging informatics.

stat.AP↗

Fast and Accurate Semi-Automatic Segmentation Tool for Brain Tumor MRIs

Segmentation, the process of delineating tumor apart from healthy tissue, is a vital part of both the clinical assessment and the quantitative analysis of brain cancers. Here, we provide an open-source algorithm (MITKats), built on the Medical Imaging Interaction Toolkit, to provide user-friendly and expedient tools for semi-automatic segmentation. To evaluate its performance against competing algorithms, we applied MITKats to 38 high-grade glioma cases from publicly available benchmarks. The similarity of the segmentations to expert-delineated ground truths approached the discrepancies among different manual raters, the theoretically maximal precision. The average time spent on each segmentation was 5 minutes, making MITKats between 4 and 11 times faster than competing semi-automatic algorithms, while retaining similar accuracy.

q-bio.QM↗