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Identifying individuals who are at high risk of cancer due to inherited germline mutations is critical for effective implementation of personalized prevention strategies. Most existing models to identify these individuals focus on specific…

Family history is a major risk factor for many types of cancer. Mendelian risk prediction models translate family histories into cancer risk predictions based on knowledge of cancer susceptibility genes. These models are widely used in…

Machine Learning · Statistics 2021-06-28 Zoe Guan , Giovanni Parmigiani , Danielle Braun , Lorenzo Trippa

Multi-gene panel testing allows many cancer susceptibility genes to be tested quickly at a lower cost making such testing accessible to a broader population. Thus, more patients carrying pathogenic germline mutations in various…

Improving existing widely-adopted prediction models is often a more efficient and robust way towards progress than training new models from scratch. Existing models may (a) incorporate complex mechanistic knowledge, (b) leverage proprietary…

Mendelian randomization (MR) is a pivotal tool in genetics, genomics, and epidemiology, leveraging genetic variants as instrumental variables to infer causal relationships between exposures and outcomes. Traditional MR methods, while…

Methodology · Statistics 2026-01-15 Bitan Sarkar , Yuchao Jiang , Tian Ge , Yang Ni

Mendelian Randomisation (MR) uses genetic variants as instrumental variables to infer causal effects of exposures on an outcome. One key assumption of MR is that the genetic variants used as instrumental variables are independent of the…

Methodology · Statistics 2025-02-21 Maximilian M Mandl , Anne-Laure Boulesteix , Stephen Burgess , Verena Zuber

Background In a study performed on multiplex Multiple Sclerosis (MS) Sardinian families to identify disease causing plasma proteins, application of Mendelian Randomization (MR) methods encounters difficulties due to relatedness of…

Mendelian randomization is the use of genetic variants to assess the existence of a causal relationship between a risk factor and an outcome of interest. Here, we focus on two-sample summary-data Mendelian randomization analyses with many…

Quantitative Methods · Quantitative Biology 2022-09-16 Apostolos Gkatzionis , Stephen Burgess , Paul J. Newcombe

Recently, there has been a resurgence of interest in rigorous algorithms for the inference of cancer progression from genomic data. The motivations are manifold: (i) growing NGS and single cell data from cancer patients, (ii) need for novel…

Machine Learning · Computer Science 2016-02-25 Daniele Ramazzotti

Mendelian randomization uses genetic variants to make causal inferences about the effect of a risk factor on an outcome. With fine-mapped genetic data, there may be hundreds of genetic variants in a single gene region any of which could be…

Methodology · Statistics 2017-07-10 Stephen Burgess , Verena Zuber , Elsa Valdes-Marquez , Benjamin B Sun , Jemma C Hopewell

The vast amount of sequencing data presently available allow the scientific community to explore a range of genetic variables that may drive and progress cancer. A myriad of predictive tools has been proposed, allowing researchers and…

Genomics · Quantitative Biology 2023-03-31 Mona Nourbakhsh , Kristine Degn , Astrid Saksager , Matteo Tiberti , Elena Papaleo

Motivation: Driver (epi)genomic alterations underlie the positive selection of cancer subpopulations, which promotes drug resistance and relapse. Even though substantial heterogeneity is witnessed in most cancer types, mutation accumulation…

We expand Mendelian Randomization (MR) methodology to deal with randomly missing data on either the exposure or the outcome variable, and furthermore with data from nonindependent individuals (eg components of a family). Our method rests on…

The use of genetic variants as instrumental variables - an approach known as Mendelian randomization - is a popular epidemiological method for estimating the causal effect of an exposure (phenotype, biomarker, risk factor) on a disease or…

Methodology · Statistics 2020-12-21 Ioan Gabriel Bucur , Tom Claassen , Tom Heskes

Introduction: The potential for multi-cancer early detection (MCED) tests to detect cancer at earlier stages is currently being evaluated in screening clinical trials. Once trial evidence becomes available, modelling will be necessary to…

Methodology · Statistics 2025-02-19 O Mandrik , S Whyte , N Kunst , A Rayner , M Harden , S Dias , K Payne , S Palmer , MO Soares

Purpose: Hereditary cancer risk is key to guiding screening and prevention strategies. Cancer risks can vary by individual due to the presence or absence of high- and moderate-risk pathogenic variants (PV) in cancer-associated genes, in…

Applications · Statistics 2025-10-29 Xueying Chen , Jianfeng Ke , Lauren Flynn , Giovanni Parmigiani , Danielle Braun

In this work, we consider the problem of predicting the course of a progressive disease, such as cancer or Alzheimer's. Progressive diseases often start with mild symptoms that might precede a diagnosis, and each patient follows their own…

Machine Learning · Computer Science 2018-03-19 Yingying Zhu , Mert R. Sabuncu

Precision medicine aims for personalized prognosis and therapeutics by utilizing recent genome-scale high-throughput profiling techniques, including next-generation sequencing (NGS). However, translating NGS data faces several challenges.…

Multi-state models of cancer natural history are widely used for designing and evaluating cancer early detection strategies. Calibrating such models against longitudinal data from screened cohorts is challenging, especially when fitting…

Computation · Statistics 2025-08-14 Raphael Morsomme , Shannon Holloway , Marc Ryser , Jason Xu

High-throughput genetic and epigenetic data are often screened for associations with an observed phenotype. For example, one may wish to test hundreds of thousands of genetic variants, or DNA methylation sites, for an association with…

Methodology · Statistics 2017-10-20 Eric F. Lock , David B. Dunson
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