Search arXivSearch

arXiv · 2505.01466

BreakLoops: A New Feature for the Multi-Gene, Multi-Cancer Family History-Based Model, Fam3Pro

Abstract

Previously, we presented PanelPRO, now known as Fam3PRO, an open-source R package for multi-gene, multi-cancer risk modeling with pedigree data. The initial release could not handle pedigrees that contained cyclic structures called loops, which occur when relatives mate. Here, we present a graph-based function called breakloops that can detect and break loops in any pedigree. The core algorithm identifies the optimal set of loop breakers when individuals in a loop have exactly one parental mating, and extends to handle cases where individuals have multiple parental matings. The algorithm transforms complex pedigrees by strategically creating clones of key individuals to disrupt cycles while minimizing computational complexity. Our extensive testing demonstrates that this new feature can handle a wide variety of pedigree structures. The breakloops function is available in Fam3Pro version 2.0.0. This advancement enables Fam3Pro to assess cancer risk in a wider range of family structures, enhancing its applicability in clinical settings

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Nicolas Kubista, Ryan Hernandez-Cancela, Jianfeng Ke, Romain Berquet, Gavin Lee, Giovanni Parmigiani, Danielle Braun. 2025-05-02. BreakLoops: A New Feature for the Multi-Gene, Multi-Cancer Family History-Based Model, Fam3Pro. https://arxiv.org/abs/2505.01466

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related papers

Wasserstein mixing of a systematic-scan random rotation sampler

We study the mixing time of a systematic-scan analogue of Kac's walk that was proposed as a fast surrogate for Haar-distributed orthogonal matrices in randomized high-dimensional algorithms and was conjectured to approach Haar measure after only logarithmically many sweeps. We show that this conjectured speed-up does not occur for convergence of the full matrix law to Haar measure in Frobenius Wasserstein distance. At fixed normalized accuracy, the mixing time lies between order $n/\log n$ and order $n$ sweeps; at fixed absolute Frobenius accuracy, the corresponding bounds are between order $n$ and order $n\log n$. More strongly, below the scale $n/\log n$, the normalized Wasserstein distance remains asymptotically at its extremal value. We also show that the output law is singular with respect to Haar measure for fewer than $n/2$ sweeps. Thus the sampler may provide effective application-specific randomization without exhibiting the much faster full-Haar mixing.

stat.CO

Bayesian Calibration with Functional Outputs Using Elastic Partial Matching

Calibrating a simulation model involves estimating its parameters by comparing model outputs with experimental data, so that simulation results faithfully reproduce the experimental observations. When the outputs are functions of time, there are multiple ways to quantify the discrepancy between experimental and simulated curves. A recent approach based on elastic functional data analysis decomposes a functional output into two components: a function temporally aligned to a template, and the corresponding warping function. This decomposition splits the problem into two independent calibration tasks, thereby addressing functional misalignment. However, it assumes that experimental and simulated curves share the same temporal support, an assumption often violated in practice when initial or end times are themselves uncertain or depend on the calibration parameters. In this work, we reinterpret the decomposition step as an approximation to a more general Bayesian calibration problem that incorporates an error term on the time axis. This perspective allows us to naturally extend the framework to a broader family of time warpings with varying initial or end times, using partial elastic alignment. We illustrate the method on a synthetic test case, comparing it with existing Bayesian calibration methods and demonstrating improved surrogate performance and error modeling. We then apply the proposed approach to the calibration of an equation of state (a thermodynamic equation relating the state variables of a material).

stat.CO

Delayed Acceptance Slice Sampling

Slice sampling is a well-established Markov chain Monte Carlo method for approximate sampling of target distributions which are only known up to a normalizing constant. The method is based on choosing a new state on a slice, i.e., a superlevel set of the given unnormalized target density (with respect to a reference measure). However, slice sampling algorithms usually require per step multiple evaluations of the target density, and thus can become computationally expensive. This is particularly the case for Bayesian inference with costly likelihoods. In this paper, we exploit deterministic approximations of the target density, which are relatively cheap to evaluate, and propose delayed acceptance versions of several common (hybrid) slice samplers. We show ergodicity of the resulting slice sampling methods, discuss the superiority of delayed acceptance (ideal) slice sampling over delayed acceptance Metropolis-Hastings algorithms, and illustrate the benefits of our novel approach in terms of improved computational efficiency in numerical experiments.

stat.CO