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1. Improved thresholds for e-values

Author

Blier-Wong, Christopher and Wang, Ruodu

Subjects
Mathematics - Statistics Theory, 62G10, 62F03, 60E15
Abstract

The rejection threshold used for e-values and e-processes is by default set to $1/\alpha$ for a guaranteed type-I error control at $\alpha$, based on Markov's and Ville's inequalities. This threshold can be wasteful in practical applications. We discuss how this threshold can be improved under additional distributional assumptions on the e-values; some of these assumptions are naturally plausible and empirically observable, without knowing explicitly the form or model of the e-values. For small values of $\alpha$, the threshold can roughly be improved (divided) by a factor of $2$ for decreasing or unimodal densities, and by a factor of $e$ for decreasing or unimodal-symmetric densities of the log-transformed e-value. Moreover, we propose to use the supremum of comonotonic e-values, which is shown to preserve the type-I error guarantee. We also propose some preliminary methods to boost e-values in the e-BH procedure under some distributional assumptions while controlling the false discovery rate. Through a series of simulation studies, we demonstrate the effectiveness of our proposed methods in various testing scenarios, showing enhanced power.

Published
2024

2. Performance of a Mobile Single-Lead Electrocardiogram Technology for Atrial Fibrillation Screening in a Semirural African Population: Insights From 'The Heart of Ethiopia: Focus on Atrial Fibrillation' (TEFF-AF) Study

Author

Pitman, Bradley M, Chew, Sok-Hui, Wong, Christopher X, Jaghoori, Amenah, Iwai, Shinsuke, Thomas, Gijo, Chew, Andrew, Sanders, Prashanthan, and Lau, Dennis H

Subjects
Information technology, T58.5-58.64, Public aspects of medicine, RA1-1270
Abstract

BackgroundAtrial fibrillation (AF) screening using mobile single-lead electrocardiogram (ECG) devices has demonstrated variable sensitivity and specificity. However, limited data exists on the use of such devices in low-resource countries. ObjectiveThe goal of the research was to evaluate the utility of the KardiaMobile device’s (AliveCor Inc) automated algorithm for AF screening in a semirural Ethiopian population. MethodsAnalysis was performed on 30-second single-lead ECG tracings obtained using the KardiaMobile device from 1500 TEFF-AF (The Heart of Ethiopia: Focus on Atrial Fibrillation) study participants. We evaluated the performance of the KardiaMobile automated algorithm against cardiologists’ interpretations of 30-second single-lead ECG for AF screening. ResultsA total of 1709 single-lead ECG tracings (including repeat tracing on 209 occasions) were analyzed from 1500 Ethiopians (63.53% [953/1500] male, mean age 35 [SD 13] years) who presented for AF screening. Initial successful rhythm decision (normal or possible AF) with one single-lead ECG tracing was lower with the KardiaMobile automated algorithm versus manual verification by cardiologists (1176/1500, 78.40%, vs 1455/1500, 97.00%; P100 bpm; 167/408, 40.93%). The sensitivity and specificity of rhythm decision using KardiaMobile automated algorithm were 80.27% (1168/1455) and 82.22% (37/45), respectively. ConclusionsThe performance of the KardiaMobile automated algorithm was suboptimal when used for AF screening. However, the KardiaMobile single-lead ECG device remains an excellent AF screening tool with appropriate clinician input and repeat tracing. Trial RegistrationAustralian New Zealand Clinical Trials Registry ACTRN12619001107112; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=378057&isReview=true

Published
2021
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3. Single-cell signatures identify microenvironment factors in tumors associated with patient outcomes.

Author

Xue, Yuanqing, Friedl, Verena, Ding, Hongxu, Wong, Christopher, and Stuart, Joshua

Subjects
CP: Cancer biology, CP: Systems biology, The Cancer Genome Atlas, cancer genomics, cancer systems biology, deconvolution, gene expression, single-cell RNA-seq, single-cell analysis, survival analysis, systems biology, tumor microenvironment, Humans, Tumor Microenvironment, Single-Cell Analysis, Neoplasms, Sequence Analysis, RNA, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Cluster Analysis
Abstract

The cellular components of tumors and their microenvironment play pivotal roles in tumor progression, patient survival, and the response to cancer treatments. Unveiling a comprehensive cellular profile within bulk tumors via single-cell RNA sequencing (scRNA-seq) data is crucial, as it unveils intrinsic tumor cellular traits that elude identification through conventional cancer subtyping methods. Our contribution, scBeacon, is a tool that derives cell-type signatures by integrating and clustering multiple scRNA-seq datasets to extract signatures for deconvolving unrelated tumor datasets on bulk samples. Through the employment of scBeacon on the The Cancer Genome Atlas (TCGA) cohort, we find cellular and molecular attributes within specific tumor categories, many with patient outcome relevance. We developed a tumor cell-type map to visually depict the relationships among TCGA samples based on the cell-type inferences.

Published
2024

4. The burden of atrial fibrillation in the Asia–Pacific region

Author

Wong, Christopher X., Tse, Hung Fat, Choi, Eue-Kuen, Chao, Tze-Fan, Inoue, Koichi, Poppe, Katrina, Tan, Eugene, Yuniadi, Yoga, Fadreguilan, Erdie, Johar, Sofian, Chan, Ngai Yin, Namboodiri, Narayan, Hossain, S. Mokaddas, He, Huang, Chantrarat, Thoranis, Bin Abd Ghani, Abdul Raqib, Davaakhuu, Narantuya, Nwe, Nwe, Irfan, Ghazala, Ton, Minh That, Gunawardena, Rohan, and Sanders, Prashanthan

Published
2024
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5. Hybrid Endo-Epicardial Therapies for Advanced Atrial Fibrillation.

Author

Wong, Christopher, Buch, Eric, Beygui, Ramin, and Lee, Randall

Subjects
atrial fibrillation, catheter ablation, hybrid AF procedure, left atrial appendage, pulmonary vein isolation
Abstract

Atrial fibrillation (AF) is a growing health problem that increases morbidity and mortality, and in most patients progresses to more advanced diseases over time. Recent research has examined the underlying mechanisms, risk factors, and progression of AF, leading to updated AF disease classification schemes. Although endocardial catheter ablation is effective for early-stage paroxysmal AF, it consistently achieves suboptimal outcomes in patients with advanced AF. Identification of the factors that lead to the increased risk of treatment failure in advanced AF has spurred the development and adoption of hybrid ablation therapies and collaborative heart care teams that result in higher long-term arrhythmia-free survival. Patients with non-paroxysmal AF, atrial remodeling, comorbidities, or AF otherwise deemed difficult to treat may find hybrid treatment to be the most effective option. Future research of hybrid therapies in advanced AF patient populations, including those with dual diagnoses, may provide further evidence establishing the safety and efficacy of hybrid endo-epicardial ablation as a first line treatment.

Published
2024

6. A representation-learning approach for insurance pricing with images

Author

Blier-Wong, Christopher, Lamontagne, Luc, and Marceau, Etienne

Subjects
Statistics - Applications
Abstract

Unstructured data are a promising new source of information that insurance companies may use to understand their risk portfolio better and improve the customer experience. However, these novel data sources are difficult to incorporate into existing ratemaking frameworks due to the size and format of the unstructured data. In this paper, we propose a framework to use street view imagery within a generalized linear model. To do so, we use representation learning to extract an embedding vector containing useful information from the image. This embedding is dense and low-dimensional, making it appropriate to use within existing ratemaking models. We find that there is useful information included in street view imagery to predict the frequency of claims for certain types of perils. This model can be used as-is in a ratemaking framework but also opens the door to future empirical research on attempting to extract the causal effect from images that lead to increased or decreased predicted claim frequencies. Throughout, we discuss the practical difficulties (technical and social) of using this type of data for insurance pricing.

Published
2023
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7. Tracking canopy chlorophyll fluorescence with a low-cost light emitting diode platform.

Author

Brissette, Logan, McHugh, Devin, Au, Jessie, Orcutt, Erica, Klein, Marie, Magney, Troy, and Wong, Christopher

Subjects
Chlorophyll fluorescence, light-emitting diode, photosynthesis, plant ecophysiology, remote sensing
Abstract

Chlorophyll fluorescence measured at the leaf scale through pulse amplitude modulation (PAM) has provided valuable insight into photosynthesis. At the canopy- and satellite-scale, solar-induced fluorescence (SIF) provides a method to estimate the photosynthetic activity of plants across spatiotemporal scales. However, retrieving SIF signal remotely requires instruments with high spectral resolution, making it difficult and often expensive to measure canopy-level steady-state chlorophyll fluorescence under natural sunlight. Considering this, we built a novel low-cost photodiode system that retrieves far-red chlorophyll fluorescence emission induced by a blue light emitting diode (LED) light source, for 2 h at night, above the canopy. Our objective was to determine if an active remote sensing-based night-time photodiode method could track changes in canopy-scale LED-induced chlorophyll fluorescence (LEDIF) during an imposed drought on a broadleaf evergreen shrub, Polygala myrtifolia. Far-red LEDIF (720-740 nm) was retrieved using low-cost photodiodes (LEDIFphotodiode) and validated against measurements from a hyperspectral spectroradiometer (LEDIFhyperspectral). To link the LEDIF signal with physiological drought response, we tracked stomatal conductance (gsw) using a porometer, two leaf-level vegetation indices-photochemical reflectance index and normalized difference vegetation index-to represent xanthophyll and chlorophyll pigment dynamics, respectively, and a PAM fluorimeter to measure photochemical and non-photochemical dynamics. Our results demonstrate a similar performance between the photodiode and hyperspectral retrievals of LEDIF (R2 = 0.77). Furthermore, LEDIFphotodiode closely tracked drought responses associated with a decrease in photochemical quenching (R2 = 0.69), Fv/Fm (R2 = 0.59) and leaf-level photochemical reflectance index (R2 = 0.59). Therefore, the low-cost LEDIFphotodiode approach has the potential to be a meaningful indicator of photosynthetic activity at spatial scales greater than an individual leaf and over time.

Published
2023

9. Sensor Observability Analysis for Maximizing Task-Space Observability of Articulated Robots

Author

Wong, Christopher Yee and Suleiman, Wael

Subjects
Computer Science - Robotics
Abstract

We propose a novel performance metric for articulated robots with distributed directional sensors called the sensor observability analysis (SOA). These robot-mounted distributed directional sensors (e.g., joint torque sensors) change their individual sensing directions as the joints move. SOA transforms individual sensors axes in joint space to provide the cumulative sensing quality of these sensors to observe each task-space axis, akin to forward kinematics for sensors. For example, certain joint configurations may align joint torque sensors in such a way that they are unable to observe interaction forces in one or more task-space axes. The resultant sensor observability performance metrics can then be used in optimization and in null-space control to avoid sensor observability singular configurations or to maximize sensor observability in particular directions. We use the specific case of force sensing in serial robot manipulators to showcase the analysis. Parallels are drawn between sensor observability and the traditional kinematic manipulability; SOA is shown to be more generalizable in terms of analysing non-joint-mounted sensors and can potentially be applied to sensor types other than for force sensing. Simulations and experiments using a custom 3-DOF robot and the Baxter robot demonstrate the utility and importance of sensor observability in physical interactions., Comment: 15 pages, 11 figures, journal paper. arXiv admin note: substantial text overlap with arXiv:2206.10798

Published
2023

10. Plant optics: underlying mechanisms in remotely sensed signals for phenotyping applications.

Author

Wong, Christopher

Subjects
Ecophysiology, machine learning, phenology, phenotyping, pigments, remote sensing, solar-induced fluorescence, stress, vegetation indices
Abstract

Optical-based remote sensing offers great potential for phenotyping vegetation traits and functions for a range of applications including vegetation monitoring and assessment. A key strength of optical-based approaches is the underlying mechanistic link to vegetation physiology, biochemistry, and structure that influences a spectral signal. By exploiting spectral variation driven by plant physiological response to environment, remotely sensed products can be used to estimate vegetation traits and functions. However, oftentimes these products are proxies based on covariance, which can lead to misinterpretation and decoupling under certain scenarios. This viewpoint will discuss (i) the optical properties of vegetation, (ii) applications of vegetation indices, solar-induced fluorescence, and machine-learning approaches, and (iii) how covariance can lead to good empirical proximation of plant traits and functions. Understanding and acknowledging the underlying mechanistic basis of plant optics must be considered as remotely sensed data availability and applications continue to grow. Doing so will enable appropriate application and consideration of limitations for the use of optical-based remote sensing for phenotyping applications.

Published
2023

12. Collective risk models with FGM dependence

Author

Blier-Wong, Christopher, Cossette, Hélène, and Marceau, Etienne

Subjects
Statistics - Applications
Abstract

We study copula-based collective risk models when the dependence structure is defined by a Farlie-Gumbel-Morgenstern (FGM) copula. By leveraging a one-to-one correspondence between the class of FGM copulas and multivariate symmetric Bernoulli distributions, we find convenient representations for the moments and Laplace-Stieltjes transform for the aggregate random variable defined from collective risk models with FGM dependence. We examine different components of this collective risk model, aiming to better understand the impact of the assumed dependence between a claim's frequency and severity. Relying on stochastic ordering, we analyze the impact of dependence on the aggregate claim amount random variable. Even if the FGM copula may only induce moderate dependence, we illustrate through numerical examples that the cumulative effect of FGM dependence can lead to substantial variations in key risk measures on aggregate random variables defined from collective risk models.

Published
2022

13. A new method to construct high-dimensional copulas with Bernoulli and Coxian-2 distributions

Author

Blier-Wong, Christopher, Cossette, Hélène, Legros, Sébastien, and Marceau, Etienne

Subjects
Mathematics - Statistics Theory
Abstract

We propose an approach to construct a new family of generalized Farlie-Gumbel-Morgenstern (GFGM) copulas that naturally scales to high dimensions. A GFGM copula can model moderate positive and negative dependence, cover different types of asymmetries, and admits exact expressions for many quantities of interest such as measures of association or risk measures in actuarial science or quantitative risk management. More importantly, this paper presents a new method to construct high-dimensional copulas based on mixtures of power functions, and may be adapted to more general contexts to construct broader families of copulas. We construct a family of copulas through a stochastic representation based on multivariate Bernoulli distributions and Coxian-2 distributions. This paper will cover the construction of a GFGM copula, study its measures of multivariate association and dependence properties. We explain how to sample random vectors from the new family of copulas in high dimensions. Then, we study the bivariate case in detail and find that our construction leads to an asymmetric modified Huang-Kotz FGM copula. Finally, we study the exchangeable case and provide some insights into the most negative dependence structure within this new class of high-dimensional copulas.

Published
2022

14. Risk aggregation with FGM copulas

Author

Blier-Wong, Christopher, Cossette, Hélène, and Marceau, Etienne

Subjects
Mathematics - Statistics Theory, Statistics - Applications
Abstract

We offer a new perspective on risk aggregation with FGM copulas. Along the way, we discover new results and revisit existing ones, providing simpler formulas than one can find in the existing literature. This paper builds on two novel representations of FGM copulas based on symmetric multivariate Bernoulli distributions and order statistics. First, we detail families of multivariate distributions with closed-form solutions for the cumulative distribution function or moments of the aggregate random variables. We order aggregate random variables under the convex order and provide methods to compute the cumulative distribution function of aggregate rvs when the marginals are discrete. Finally, we discuss risk-sharing and capital allocation, providing numerical examples for each.

Published
2022

15. Generating function method for the efficient computation of expected allocations

Author

Blier-Wong, Christopher, Cossette, Hélène, and Marceau, Etienne

Subjects
Statistics - Applications
Abstract

Consider a risk portfolio with aggregate loss random variable $S=X_1+\dots +X_n$ defined as the sum of the $n$ individual losses $X_1, \dots, X_n$. The expected allocation, $E[X_i \times 1_{\{S = k\}}]$, for $i = 1, \dots, n$ and $k \in \mathbb{N}$, is a vital quantity for risk allocation and risk-sharing. For example, one uses this value to compute peer-to-peer contributions under the conditional mean risk-sharing rule and capital allocated to a line of business under the Euler risk allocation paradigm. This paper introduces an ordinary generating function for expected allocations, a power series representation of the expected allocation of an individual risk given the total risks in the portfolio when all risks are discrete. First, we provide a simple relationship between the ordinary generating function for expected allocations and the probability generating function. Then, leveraging properties of ordinary generating functions, we reveal new theoretical results on closed-formed solutions to risk allocation problems, especially when dealing with Katz or compound Katz distributions. Then, we present an efficient algorithm to recover the expected allocations using the fast Fourier transform, providing a new practical tool to compute expected allocations quickly. The latter approach is exceptionally efficient for a portfolio of independent risks.

Published
2022

16. TSWIFT: Tower Spectrometer on Wheels for Investigating Frequent Timeseries for high-throughput phenotyping of vegetation physiology

Author

Wong, Christopher YS, Jones, Taylor, McHugh, Devin P, Gilbert, Matthew E, Gepts, Paul, Palkovic, Antonia, Buckley, Thomas N, and Magney, Troy S

Subjects
High-throughput phenotyping, Hyperspectral reflectance, NDVI, PRI, Remote sensing, SIF, Vegetation indices, Biochemistry and Cell Biology, Plant Biology, Agricultural Biotechnology, Plant Biology & Botany
Abstract

BackgroundRemote sensing instruments enable high-throughput phenotyping of plant traits and stress resilience across scale. Spatial (handheld devices, towers, drones, airborne, and satellites) and temporal (continuous or intermittent) tradeoffs can enable or constrain plant science applications. Here, we describe the technical details of TSWIFT (Tower Spectrometer on Wheels for Investigating Frequent Timeseries), a mobile tower-based hyperspectral remote sensing system for continuous monitoring of spectral reflectance across visible-near infrared regions with the capacity to resolve solar-induced fluorescence (SIF).ResultsWe demonstrate potential applications for monitoring short-term (diurnal) and long-term (seasonal) variation of vegetation for high-throughput phenotyping applications. We deployed TSWIFT in a field experiment of 300 common bean genotypes in two treatments: control (irrigated) and drought (terminal drought). We evaluated the normalized difference vegetation index (NDVI), photochemical reflectance index (PRI), and SIF, as well as the coefficient of variation (CV) across the visible-near infrared spectral range (400 to 900 nm). NDVI tracked structural variation early in the growing season, following initial plant growth and development. PRI and SIF were more dynamic, exhibiting variation diurnally and seasonally, enabling quantification of genotypic variation in physiological response to drought conditions. Beyond vegetation indices, CV of hyperspectral reflectance showed the most variability across genotypes, treatment, and time in the visible and red-edge spectral regions.ConclusionsTSWIFT enables continuous and automated monitoring of hyperspectral reflectance for assessing variation in plant structure and function at high spatial and temporal resolutions for high-throughput phenotyping. Mobile, tower-based systems like this can provide short- and long-term datasets to assess genotypic and/or management responses to the environment, and ultimately enable the spectral prediction of resource-use efficiency, stress resilience, productivity and yield.

Published
2023

17. Ventriculoatrial Block and His-His Changes During Supraventricular Tachycardia Diagnostic and Mechanistic Implications

Author

Wong, Christopher X, Higuchi, Satoshi, Nagashima, Koichi, Kaneko, Yoshiaki, Gerstenfeld, Edward P, and Scheinman, Melvin M

Subjects
Heart Disease, Cardiovascular, AH, atrio-His, AV, atrioventricular, AVNRT, AVNRT, atrioventricular nodal re-entrant tachycardia, HA, His-atrial, HH, His-His, HV, His-ventricular, His, LBBB, left bundle branch block, NF, nodofascicular, NV, nodoventricular, ORT, orthodromic re-entry, RBBB, right bundle branch block, SVT, supraventricular tachycardia, VA, ventriculoatrial, nodoventricular or nodofascicular, supraventricular tachycardia, ventriculoatrial block
Abstract

Supraventricular tachycardia (SVT) with ventriculoatrial (VA) block can represent a diagnostic challenge. We present a case of SVT where His-His interval shortening was repeatedly observed during episodes of VA block. This novel observation is more diagnostically suggestive of atrioventricular nodal re-entrant tachycardia, as opposed to orthodromic re-entry using a nodofascicular or nodoventricular pathway where a constant His-His is recorded during episodes of VA block. (Level of Difficulty: Intermediate.).

Published
2023

18. Hyperspectral Remote Sensing for Phenotyping the Physiological Drought Response of Common and Tepary Bean

Author

Wong, Christopher YS, Gilbert, Matthew E, Pierce, Marshall A, Parker, Travis A, Palkovic, Antonia, Gepts, Paul, Magney, Troy S, and Buckley, Thomas N

Abstract

Proximal remote sensing offers a powerful tool for high-throughput phenotyping of plants for assessing stress response. Bean plants, an important legume for human consumption, are often grown in regions with limited rainfall and irrigation and are therefore bred to further enhance drought tolerance. We assessed physiological (stomatal conductance and predawn and midday leaf water potential) and ground- and tower-based hyperspectral remote sensing (400 to 2,400 nm and 400 to 900 nm, respectively) measurements to evaluate drought response in 12 common bean and 4 tepary bean genotypes across 3 field campaigns (1 predrought and 2 post-drought). Hyperspectral data in partial least squares regression models predicted these physiological traits (R 2 = 0.20 to 0.55; root mean square percent error 16% to 31%). Furthermore, ground-based partial least squares regression models successfully ranked genotypic drought responses similar to the physiologically based ranks. This study demonstrates applications of high-resolution hyperspectral remote sensing for predicting plant traits and phenotyping drought response across genotypes for vegetation monitoring and breeding population screening.

Published
2023

19. Vision- and tactile-based continuous multimodal intention and attention recognition for safer physical human-robot interaction

Author

Wong, Christopher Yee, Vergez, Lucas, and Suleiman, Wael

Subjects
Computer Science - Robotics
Abstract

Employing skin-like tactile sensors on robots enhances both the safety and usability of collaborative robots by adding the capability to detect human contact. Unfortunately, simple binary tactile sensors alone cannot determine the context of the human contact -- whether it is a deliberate interaction or an unintended collision that requires safety manoeuvres. Many published methods classify discrete interactions using more advanced tactile sensors or by analysing joint torques. Instead, we propose to augment the intention recognition capabilities of simple binary tactile sensors by adding a robot-mounted camera for human posture analysis. Different interaction characteristics, including touch location, human pose, and gaze direction, are used to train a supervised machine learning algorithm to classify whether a touch is intentional or not with an F1-score of 86%. We demonstrate that multimodal intention recognition is significantly more accurate than monomodal analyses with the collaborative robot Baxter. Furthermore, our method can also continuously monitor interactions that fluidly change between intentional or unintentional by gauging the user's attention through gaze. If a user stops paying attention mid-task, the proposed intention and attention recognition algorithm can activate safety features to prevent unsafe interactions. We also employ a feature reduction technique that reduces the number of inputs to five to achieve a more generalized low-dimensional classifier. This simplification both reduces the amount of training data required and improves real-world classification accuracy. It also renders the method potentially agnostic to the robot and touch sensor architectures while achieving a high degree of task adaptability., Comment: 11 pages, 8 figures, preprint under review

Published
2022

20. Sensor Observability Index: Evaluating Sensor Alignment for Task-Space Observability in Robotic Manipulators

Author

Wong, Christopher Yee and Suleiman, Wael

Subjects
Computer Science - Robotics
Abstract

In this paper, we propose a preliminary definition and analysis of the novel concept of sensor observability index. The goal is to analyse and evaluate the performance of distributed directional or axial-based sensors to observe specific axes in task space as a function of joint configuration in serial robot manipulators. For example, joint torque sensors are often used in serial robot manipulators and assumed to be perfectly capable of estimating end effector forces, but certain joint configurations may cause one or more task-space axes to be unobservable as a result of how the joint torque sensors are aligned. The proposed sensor observability provides a method to analyse the quality of the current robot configuration to observe the task space. Parallels are drawn between sensor observability and the traditional kinematic Jacobian for the particular case of joint torque sensors in serial robot manipulators. Although similar information can be retrieved from kinematic analysis of the Jacobian transpose in serial manipulators, sensor observability is shown to be more generalizable in terms of analysing non-joint-mounted sensors and other sensor types. In addition, null-space analysis of the Jacobian transpose is susceptible to false observability singularities. Simulations and experiments using the robot Baxter demonstrate the importance of maintaining proper sensor observability in physical interactions., Comment: 7 pages, 5 figures, conference paper

Published
2022
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21. Exchangeable FGM copulas

Author

Blier-Wong, Christopher, Cossette, Hélène, and Marceau, Etienne

Subjects
Mathematics - Statistics Theory
Abstract

Copulas are a powerful tool to model dependence between the components of a random vector. One well-known class of copulas when working in two dimensions is the Farlie-GumbelMorgenstern (FGM) copula since their simple analytic shape enables closed-form solutions to many problems in applied probability. However, the classical definition of high-dimensional FGM copula does not enable a straightforward understanding of the effect of the copula parameters on the dependence, nor a geometric understanding of their admissible range. We circumvent this issue by studying the FGM copula from a probabilistic approach based on multivariate Bernoulli distributions. This paper studies high-dimensional exchangeable FGM copulas, a subclass of FGM copulas. We show that dependence parameters of exchangeable FGM can be expressed as convex hulls of a finite number of extreme points and establish partial orders for different exchangeable FGM copulas (including maximal and minimal dependence). We also leverage the probabilistic interpretation to develop efficient sampling and estimating procedures and provide a simulation study. Throughout, we discover geometric interpretations of the copula parameters that assist one in decoding the dependence of high-dimensional exchangeable FGM copulas.

Published
2022

24. Transcriptional profiling of matched patient biopsies clarifies molecular determinants of enzalutamide-induced lineage plasticity.

Author

Westbrook, Thomas C, Guan, Xiangnan, Rodansky, Eva, Flores, Diana, Liu, Chia Jen, Udager, Aaron M, Patel, Radhika A, Haffner, Michael C, Hu, Ya-Mei, Sun, Duanchen, Beer, Tomasz M, Foye, Adam, Aggarwal, Rahul, Quigley, David A, Youngren, Jack F, Ryan, Charles J, Gleave, Martin, Wang, Yuzhuo, Huang, Jiaoti, Coleman, Ilsa, Morrissey, Colm, Nelson, Peter S, Evans, Christopher P, Lara, Primo, Reiter, Robert E, Witte, Owen, Rettig, Matthew, Wong, Christopher K, Weinstein, Alana S, Uzunangelov, Vlado, Stuart, Josh M, Thomas, George V, Feng, Felix Y, Small, Eric J, Yates, Joel A, Xia, Zheng, and Alumkal, Joshi J

Subjects
Cell Line, Tumor, Humans, Benzamides, Nitriles, Phenylthiohydantoin, Receptors, Androgen, RNA, Biopsy, Drug Resistance, Neoplasm, Male, E2F1 Transcription Factor, Androgen Receptor Antagonists, Prostatic Neoplasms, Castration-Resistant, Prostate Cancer, Genetics, Urologic Diseases, Cancer, Clinical Research, 2.1 Biological and endogenous factors, Aetiology
Abstract

The androgen receptor (AR) signaling inhibitor enzalutamide (enza) is one of the principal treatments for metastatic castration-resistant prostate cancer (CRPC). Several emergent enza clinical resistance mechanisms have been described, including lineage plasticity in which the tumors manifest reduced dependency on the AR. To improve our understanding of enza resistance, herein we analyze the transcriptomes of matched biopsies from men with metastatic CRPC obtained prior to treatment and at progression (n = 21). RNA-sequencing analysis demonstrates that enza does not induce marked, sustained changes in the tumor transcriptome in most patients. However, three patients' progression biopsies show evidence of lineage plasticity. The transcription factor E2F1 and pathways linked to tumor stemness are highly activated in baseline biopsies from patients whose tumors undergo lineage plasticity. We find a gene signature enriched in these baseline biopsies that is strongly associated with poor survival in independent patient cohorts and with risk of castration-induced lineage plasticity in patient-derived xenograft models, suggesting that tumors harboring this gene expression program may be at particular risk for resistance mediated by lineage plasticity and poor outcomes.

Published
2022

25. Analysis of germline-driven ancestry-associated gene expression in cancers

Author

Chambwe, Nyasha, Sayaman, Rosalyn W, Hu, Donglei, Huntsman, Scott, Network, The Cancer Genome Analysis, Carrot-Zhang, Jian, Berger, Ashton C, Han, Seunghun, Meyerson, Matthew, Damrauer, Jeffrey S, Hoadley, Katherine A, Felau, Ina, Demchok, John A, Mensah, Michael KA, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Knijnenburg, Theo A, Robertson, A Gordon, Yau, Christina, Benz, Christopher, Huang, Kuan-lin, Newberg, Justin Y, Frampton, Garrett M, Mashl, R Jay, Ding, Li, Romanel, Alessandro, Demichelis, Francesca, Zhou, Wanding, Laird, Peter W, Shen, Hui, Wong, Christopher K, Stuart, Joshua M, Lazar, Alexander J, Le, Xiuning, Oak, Ninad, Kemal, Anab, Caesar-Johnson, Samantha, Zenklusen, Jean C, Ziv, Elad, Beroukhim, Rameen, and Cherniack, Andrew D

Subjects
Biological Sciences, Health Sciences, Genetics, Human Genome, Biotechnology, Cancer, Good Health and Well Being, Gene Expression, Germ Cells, Humans, Neoplasms, Quantitative Trait Loci, RNA, Messenger, Cancer Genome Analysis Network, Bioinformatics, Computer sciences, Genomics, RNAseq, Sequence analysis
Abstract

Differential mRNA expression between ancestry groups can be explained by both genetic and environmental factors. We outline a computational workflow to determine the extent to which germline genetic variation explains cancer-specific molecular differences across ancestry groups. Using multi-omics datasets from The Cancer Genome Atlas (TCGA), we enumerate ancestry-informative markers colocalized with cancer-type-specific expression quantitative trait loci (e-QTLs) at ancestry-associated genes. This approach is generalizable to other settings with paired germline genotyping and mRNA expression data for a multi-ethnic cohort. For complete details on the use and execution of this protocol, please refer to Carrot-Zhang et al. (2020), Robertson et al. (2021), and Sayaman et al. (2021).

Published
2022

26. Elder Wellness during COVID-19: A Student-Directed Intergenerational Virtual Discussion Group

Author

Shenoi, Rachel M., Wong, Christopher K., and Selleck, Sarah E.

Abstract

Objective: The COVID-19 pandemic saw increased loneliness and social isolation among older adults as activities and visitor opportunities for residential communities closed down. Health professional students have limited access to geriatric education in coursework and clinical experiences. The Recreation and Education Network for Elder Wellness (RENEW) programme was created by medical students at Baylor College of Medicine in Houston, Texas, aiming to increase engagement and cross-generational communication with older adults, while also decreasing social isolation and loneliness. Method: The RENEW programme included Zoom sessions with two Houston retirement communities led by student facilitators enrolled in medical, dental, and undergraduate programmes on a variety of topics of interest for the residents. Pre- and post-surveys were sent to participants and requested non-identifying biographical data and included the Revised UCLA Loneliness Scale. Results: Facilitators and participants expressed high satisfaction with the programme. Survey results on the Revised UCLA Loneliness Scale showed that participants had an overall decreased loneliness score after participation in RENEW. Student facilitators reported increased exposure to care of older adults and self-reported confidence in communicating with this population. Conclusions: The RENEW model is a collaborative, bidirectional educational tool for older adults and students with possible applications following the COVID-19 pandemic.

Published
2023
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28. Introduction

Author

Wong, Christopher J., Jackson, Sara L., Wong, Christopher J., editor, and Jackson, Sara L., editor

Published
2023
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34. Sex and ethnic disparities in hepatitis B evaluation and treatment across the world

Author

Kudaravalli, Sahith, Huang, Daniel Q., Yeh, Ming-Lun, Trinh, Lindsey, Tsai, P.C., Hsu, Yao-Chun, Kam, Leslie Y., Nguyen, Vy H., Ogawa, Eiichi, Lee, Dong Hyun, Ito, Takanori, Watanabe, Tsunamasa, Enomoto, Masaru, Preda, Carmen Monica, Ko, Michael K.L., Wan-Hin Hui, Rex, Atsukawa, Masanori, Suzuki, Takanori, Marciano, Sebastian, Barreira, Ana, Do, Son, Uojima, Haruki, Takahashi, Hirokazu, Quek, Sabrina X.Z., Toe Wai Khine, Htet Htet, Ishigami, Masatoshi, Itokawa, Norio, Go, Min Seok, Kozuka, Ritsuzo, Marin, Raluca Ioana, Sandra, Irina, Li, Jiayi, Zhang, Jian Q., Wong, Christopher, Yoshimaru, Yoko, Vo, Dang K.H., Tseng, Cheng-Hao, Lee, Chul-jin, Inoue, Kaori, Maeda, Mayumi, Hoang, Joseph K., Chau, Angela, Chuang, Wan-Long, Dai, Chia-Yen, Huang, Jee-Fu, Huang, Chung-Feng, Buti, Maria, Tanaka, Yasuhito, Gadano, Adrian Carlos, Yuen, Man-Fung, Cheung, Ramsey, Lim, Seng Gee, Trinh, Huy N., Toyoda, Hidenori, Yu, Ming-Lung, and Nguyen, Mindie H.

Published
2024
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35. Colloidal silica grout for the formation of hydraulic barriers : an investigation of the hydro-mechanical and gelling behaviour

Author

Wong, Christopher Shi Kiu and El Mountassir, Gráinne

Abstract

Hazardous waste sources such as heavy metals, chemical substances, gases, asbestos, and radioactive substances situated in the subsurface due to historical urban and industrial activities have contributed to a considerable legacy of contaminated sites both in the UK and worldwide. It is estimate that in England and Wales there is potentially 300,000 ha across 325,000 sites of contaminated land (Environment Agency, 2005). Furthermore, the numbers of potentially contaminated sites may increase from future closures and decommissioning of sites across various industries such as nuclear facilities (NDA, 2016). Contamination and its implications cannot be avoided; thus, remediation of contaminated waste sites and improvements to current technologies can provide global environmental benefits (Rivett et al., 2002). The Sellafield site located in northwest England is regarded to be one of "the most hazardous places in Europe" (McKie, 2009). With the most hazardous facilities including four legacy ponds, silos that hold large quantities of nuclear material, and stores housing the UK plutonium inventory. The Nuclear Decommissioning Authority (NDA) estimate costs of £121 billion for the completion of decommissioning work at the Sellafield site by 2120 (NAO, 2018). Statutory guidelines by DEFRA (2012) outline the legal obligations to minimise the risk posed to both humans and the environment from land contamination. In addition, specific industrial licence regulators state requirements of redundancy in the case of leakages (i.e. secondary containment systems) (ONR, 2016). Assessment of contaminated land and appropriate remediation method can be examined by considering three key factors: hazard, pathway, and receptor. The relationship between the three factors is known as pollutant linkage and can be used to determine risks (Angel et al., 2005, DEFRA, 2012). Remediation strategies adopted to minimise or control risks in contaminated land scenario typically comprise three main techniques: hazard reduction (e.g. removal or treatment of the contaminant), pathway modification (e.g containment barrier prevent contact between receptor and hazard), or receptor control (e.g modify the location or nature of the receptor). However, it is usually very difficult to modify receptor behaviour (i.e. humans/biological receptors). Therefore, remediation technologies generally fall into two categories: (i) hazard reduction and (ii) pathway modification. Hazard reduction methods include pump and treat, sparging, and venting. These methods can be implemented to remove and treat contaminated groundwater and volatile compounds. However, contaminants may still remain in situ sorbed onto soil particles. Permeable reactive barriers may also be used as an engineered treatment zone placed to remediate contaminated groundwater as it flows through utilising the mechanism of sorption, oxidation/reduction, precipitation, fixation, and biodegradation. Several other methods also exist including electro-remediation and phytoremediation treatment, these techniques can typically be applied both in-situ and ex-situ. (Nathanail et al., 2007, DEFRA, 2010, Angel et al., 2005). A common strategy for pathway modification is excavation and disposal, the main advantage is that it removes the contaminated soils and breaks the contaminant pathway. However, high costs with transporting and handling of waste, in addition to on site restrictions of operational structures or services are driving the development of alternative remediation strategies (SEPA, 2017). Hydraulic containment is another method of pathway modification utilising pumping to lower the water table to isolate contamination. However, the use of pumps to achieve hydraulic containment can be expensive due to the need for long-term intervention and monitoring. Physical containment barriers use low permeability barriers constructed in the subsurface to inhibit contaminant transport by controlling ground water flow (Persoff et al., 1998, Mulligan et al., 2001). For sites, with very large volumes of contamination or contamination beneath remaining buildings containment may be the only practical option. The advantage of physical containment systems is that they can be widely applied to sites with a range of different contaminants.

Published
2022
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38. Geographic ratemaking with spatial embeddings

Author

Blier-Wong, Christopher, Cossette, Hélène, Lamontagne, Luc, and Marceau, Etienne

Subjects
Statistics - Applications, Statistics - Machine Learning
Abstract

Spatial data is a rich source of information for actuarial applications: knowledge of a risk's location could improve an insurance company's ratemaking, reserving or risk management processes. Insurance companies with high exposures in a territory typically have a competitive advantage since they may use historical losses in a region to model spatial risk non-parametrically. Relying on geographic losses is problematic for areas where past loss data is unavailable. This paper presents a method based on data (instead of smoothing historical insurance claim losses) to construct a geographic ratemaking model. In particular, we construct spatial features within a complex representation model, then use the features as inputs to a simpler predictive model (like a generalized linear model). Our approach generates predictions with smaller bias and smaller variance than other spatial interpolation models such as bivariate splines in most situations. This method also enables us to generate rates in territories with no historical experience.

Published
2021
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39. Rethinking Representations in P&C Actuarial Science with Deep Neural Networks

Author

Blier-Wong, Christopher, Baillargeon, Jean-Thomas, Cossette, Hélène, Lamontagne, Luc, and Marceau, Etienne

Subjects
Statistics - Applications
Abstract

Insurance companies gather a growing variety of data for use in the insurance process, but most traditional ratemaking models are not designed to support them. In particular, many emerging data sources (text, images, sensors) may complement traditional data to provide better insights to predict the future losses in an insurance contract. This paper presents some of these emerging data sources and presents a unified framework for actuaries to incorporate these in existing ratemaking models. Our approach stems from representation learning, whose goal is to create representations of raw data. A useful representation will transform the original data into a dense vector space where the ultimate predictive task is simpler to model. Our paper presents methods to transform non-vectorial data into vectorial representations and provides examples for actuarial science., Comment: 27 pages, 16 figures

Published
2021

40. Analytical protocol to identify local ancestry-associated molecular features in cancer

Author

Carrot-Zhang, Jian, Han, Seunghun, Zhou, Wanding, Damrauer, Jeffrey S, Kemal, Anab, Network, Cancer Genome Atlas Analysis, Berger, Ashton C, Meyerson, Matthew, Hoadley, Katherine A, Felau, Ina, Caesar-Johnson, Samantha, Demchok, John A, Mensah, Michael KA, Tarnuzzer, Roy, Wang, Zhining, Yang, Liming, Zenklusen, Jean C, Chambwe, Nyasha, Knijnenburg, Theo A, Robertson, A Gordon, Yau, Christina, Benz, Christopher, Huang, Kuan-lin, Newberg, Justin, Frampton, Garret, Mashl, R Jay, Ding, Li, Romanel, Alessandro, Demichelis, Francesca, Sayaman, Rosalyn W, Ziv, Elad, Laird, Peter W, Shen, Hui, Wong, Christopher K, Stuart, Joshua M, Lazar, Alexander J, Le, Xiuning, Oak, Ninad, Cherniack, Andrew D, and Beroukhim, Rameen

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Health Sciences, Oncology and Carcinogenesis, Health Disparities, Human Genome, Cancer, Cancer Genomics, Minority Health, 4.1 Discovery and preclinical testing of markers and technologies, 2.1 Biological and endogenous factors, Genetics, Population, Genome, Human, Genomics, Genotyping Techniques, Humans, Neoplasms, Phenotype, Cancer Genome Atlas Analysis Network, Bioinformatics
Abstract

People of different ancestries vary in cancer risk and outcome, and their molecular differences may indicate sources of these variations. Determining the "local" ancestry composition at each genetic locus across ancestry-admixed populations can suggest causal associations. We present a protocol to identify local ancestry and detect the associated molecular changes, using data from the Cancer Genome Atlas. This workflow can be applied to cancer cohorts with matched tumor and normal data from admixed patients to examine germline contributions to cancer. For complete details on the use and execution of this protocol, please refer to Carrot-Zhang et al. (2020).

Published
2021

41. Efficacy and safety of aldosterone synthase inhibition with and without empagliflozin for chronic kidney disease: a randomised, controlled, phase 2 trial

Author

Tuttle, Katherine R, Hauske, Sibylle J, Canziani, Maria Eugenia, Caramori, Maria Luiza, Cherney, David, Cronin, Lisa, Heerspink, Hiddo J L, Hugo, Christian, Nangaku, Masaomi, Rotter, Ricardo Correa, Silva, Arnold, Shah, Shimoli V, Sun, Zhichao, Urbach, Dorothea, de Zeeuw, Dick, Rossing, Peter, SZETO, Cheuk Chun, Echeverri, Diego, Martin, Edouard, Yee, Ming Li, Wah, William, Wang, Ray, Chacko, Bobby, Swaminathan, Shriram, MacIsaac, Richard, Hashimura, Hikaru, Ward, Glenn, De Vusser, Katrien, Claes, Kathleen, Kuypers, Dirk, Meijers, Björn, Van Craenenbroeck, Amaryllis, Hilbrands, Robert, Debroye, Corinne, Wissing, Karl Martin, Jadoul, Michel, Demoulin, Nathalie, Treille De Grandsaigne, Serge, Beklevic, Ishak, Marcoux, Diane, Liénart, Fabienne, Daper, Claude, De Brouckere, Véronique, Heureux, Mercédès, Felicio, Joao, Felicio, Karem Mileo, Leite, Daniella, Melo, Franciane, Queiroz, Natercia, Souza, Ana Carolina, Vieira, Jocyelle, Franco, Roberto, Mendes, Adriana, Picolli, Giovana, Canani, Luis Henrique, Sartori, Carla, Valenti, Adriana, Eliaschewitz, Freddy, Bona, Renata, Franco, Denise, Ludovico Costa de Castro, Denise, Magalhaes, Vanessa, Oliveira, Marcelo, Sampaio, Célia Regina, Visconti, Guilherme, Halpern, Bruno, Nihei, Camila, Pessoa, Bruna, Seraphim, Carlos, Santos, Daniel, Brito, Claudia, Douverny, Joao, Colella, Marina, Gazeta, Cristina, Vercia, Monique, Watanabe, Renato, Temelkova, Theodora, Kjurkchiev, Dimo, Statkova, Silviya, Popov, Iliya, Radeva, Radosveta, Arabadzhiev, Lachezar, Binova, Mariya, Bosilkov, Aleksandar, Koleva-Stoicheva, Neli, Ivanov, Ivaylo, Ivanova, Zornitsa, Kotseva, Viktoria, Spasov, Petar, Tsvetkov, Ivaylo, Jolly, Shivinder, Bailey, Gordon, Ye, Zhiming, Niu, Jianying, Li, Hongmei, Wu, Qing, Liao, Bing, Hao, Chuanming, Lai, Lingyun, Xu, Yunyu, Zhang, Min, Li, Yiwen, Liu, Bo, Shao, Lina, Chen, Wei, Wu, Haishan, Pirchala, Marian, Skarpova, Iva, Hraskova, Marketa, Soukupova, Simoneta, Veberova, Lucie, Drasnar, Tomas, Falc, Matej, Racz, Blazej, Votocek, Stepan, Weissova, Danica, Syc-Krivanova, Lenka, Slezak, Dagmar, Kantola, Ilkka, Nieminen, Sakari, Anttonen, Milla, Taurio, Jyrki, Lahtela, Jorma, Tsimihodimos, Vasileios, Balafa, Olga, Dounousi, Evangelia, Sakkou, Sissy, Tentolouris, Nikolaos, Siafarikas, Christos, Siami, Evangelia, Doupis, Ioannis, Angelopoulos, Theodoros, Georgoulias, Christodoulos, Pall, Denes, Esze, Regina, Kobling, Tamas, Varadi, Zita, Zsiros, Noemi, Vass, Viktor, Balo, Timea, Csanyi, Erika, Ory, Ivan, Pall, Istvan, Patai, Valentina, Zeak, Zsuzsanna, Takacs, Istvan, Petho, Akos, Szili, Balazs, Koranyi, Laszlo, Bezzegh, Katalin, Pauer, Jozsef, Peterfai, Eva, Konyves, Laszlo, Szoke, Brigitta, Hajdu, Csaba, Kalman, Krisztina, Yadav, Raj, Saxena, Navneet, Bhattacharya, Meenakshi, Sharma, Bal, Thomas, Nihal, K, Felix Jebasingh, Kapoor, Nitin, Kurian, Mathews E., Paul, Jinson, Ramesh, Priyadharshini, Varghese, Sheeba, Shibusawa, Nobuyuki, Nishi, Hiroshi, Noritake, Nobuyasu, Oda, Takashi, Okamoto, Hideki, Kasuga, Hirotake, Hori, Hiroshi, Ito, Yukiko, Mizukoshi, Toshihiro, Ishii, Hideto, Han, Seung Hyeok, Kim, Hyung Woo, Oh, Kook-Hwan, Han, Seung Seok, Han, Sang Youb, Cha, Dae Ryong, Cha, Jin Joo, Kwon, Soon-Kil, Cho, Hyunjeong, Kim, Hye-Young, Kim, Sun Moon, Lee, Jung Pyo, Lee, Jeonghwan, Lee, Li Yuan, Chang, Meng Lee, Laang, Shian Tuck, Tan, Zhao Zhi, Ahmad Rosdi, Hajar, Mohammad Ismail, Siti Hafizah, Simatherai, Devamalar, Tay, Ju Fan, Wong, Eddie, Fook Sem, Yakob, Suryati, Abdul Sukur, Noorhafini, Anuar, Amalina, Md. Rasid, Syaliza, Mushaddik, Irma Liyana, Mustafar, Ruslinda, Abu Shamsi, Muhammad Yusuf, Fong, Voon Ken, Kamaruzaman, Lydia, Mohd, Rozita, Wan Daud, Wan Rohaslizan, Wan Hassan, Wan Hasnul Halimi, Ab Hamid, Suhaidarwani, Abdullah, Muhammad Nabil, Yusoff, Mohd Yusran, Ramanathan, G R Letchuman, Lee, Kim Yen, Wan Ismail, Wan Fadhilah, Morales Villegas, Enrique, Ramirez Baez, Rubria, Vital Lopez, Jorge, Arias Delgadillo, Cristhian, Herrera Marmolejo, Marisol, Parra Perez, Rosa, Alpizar Salazar, Melchor, Flores Montealegre, Ana, Galvan Magaña, Jose, Gutierrez Tlapale, Minerva, Reyes Munguia, Daniela, Witczak, Bartlomiej, Gøransson, Lasse, Strand Thorsen, Inga, Caringal, Clodoaido, Villardo, Mario, Toledo, Ronaldo, Dijamco, Emerlinda Fausto, De Asis, Norman Cornelio, Kuizon, Angelica, Catindig, Elizabeth Ann, Perez, Ronald, Aquitania, Grace, Pableo, Jimrie David, Sanchez, Jay Karlou, Czernecka, Ewa, Cegiel, Aleksandra, Knychas, Dorota, Ochnio, Malgorzata, Kuligowska-Jakubowska, Monika, Cesarz, Marek, Kowalewska-Celejewska, Milena, Masajtis-Zagajewska, Anna, Jankowski, Lukasz, Ojrzanowski, Marcin, Olszewska-Jander, Magdalena, Skokowska, Ewa, Giermakowska-Samek, Malgorzata, Luchowska, Elzbieta, Patkowska, Renata, Sekulska, Marzenna, Marczuk-Krynicka, Dorota, Marciniak, Andrzej, Barwijuk, Michal, Myslicki, Marcin, Siek, Michal, Wronska, Danuta, Tomsia-Goncerz, Jadwiga, Wronski, Krzysztof, Junik, Roman, Dzialak, Szymon, Kurlapska, Ewelina, Malecha, Wieslaw, Suwala, Szymon, Branco, Patrícia, Birne, Rita, Raposo, João, Ferreira, Marta, Alexandrino, Henrique, Alves, Helena, Correia, Sara, Oliveira, Maria João, Ramalho, Diogo, Tavares, Patricia, Coetzee, Kathleen, Blignaut, Sue, Viljoen, Winifred, Potgieter, Elsje, Malherbe, Elmien, Ortiz Arduán, Alberto, Goma Garcés, Elena, Pérez, María, Santamaría, Rafael, López López, Isabel, Pendón de Mier, Victoria, Rodelo Haad, Cristian, Marques, María, Domènech, Esther, Portoles, Josep Maria, Soler, María José, Agraz, Irene, Azancot, María Antonieta, Bermejo, Sheila, Bolufer, Mónica, López, Marina, Ramos, Natalia, Toapanta, Néstor, Cigarrán Guldris, Secundino, Primo, Juan Carlos, Pérez, Luis Enrique, Rebollido Fernández, María, Holmer, Helene, Bruchfeld, Annette, Rofors, Justus, Tengmark, Bengt-Olov, Wuerzner, Gregoire, Leanizbarrutia, Garazi, Ozturk, Savas, Guler, Nurana, Safak, Seda, Lee, Keung, Campbell, Stephen, Siddiqui, Imran, Abbasi, Nadia, Tahir, Faiza, Azizad, Masoud, Jackson, Timothy, Everhart, Brian, Oliver, Michael, Rust, William, Sniezek, Matthew, Arif, Ahmed, Syed, Mohammed, Bhasin, Nitin, Bien, Michael, Gallego, Claudio, Jamal, Aamir, Moghadam, Mojtaba, Rizvi, Abid, Rizvi, Amna, Rizvi, Syed, Wong, Christopher, Lucas, Kathryn, Buery, Andrea, Chang, Ku-Lang, Presswood, Claire, Smith, Justin, Doshi, Ankur, Parikh, Manish, Wallace, Jeannine, Krishna, Arvind, Daugherty, Heidi, Fearday, Aaron, Keller, Christopher, Meng, Jerry, Nielsen, Alexandra, Rovner, Sergio, Almeida, Javier, Marranzini, Benito, Selby, Lisa, Yablon, Zachary, Jean-Louis, Daphne, Kotzker, Wayne, Perez, Chabely, Richards, Marc, Rosario, Reinaldo, Marcus, Roy, Okechukwu, Chike, Ross, Dennis, Gromala, Rachel, Reed, Matthew, Weber, Lisa, Nazeer, Imran, Kumar, Prashant, Mir, Muhammad, Shea, Heidi, Hart, Amanda, Wiebel, Jaime, Kooienga, Laura, Newsome, Britt, Suyumova, Irina, Alvarez, German, Bireddy, Venkata, Lansang, Maria, Mandry, Jose, Freire, Maria, Herrera Albornoz, Oscarina, Desai, Anant, Gandhi, Dayan, Rajan, Sibu, Raymond, Louis, Posada, Jorge, Garcia-Mayol, Luis, Gutierrez-Alsina, Rodolfo, Fernandez, Juan, Bruce, Kendaling, Cuellar, Juan, Ranz y Alvarez, Maria, Bartolacci, Ines, Pautasso, Mauro, Stoppa, Daniela, Riella, Miguel, Barbosa, Maria, Harcsa, Eleonora, Gulati, Yuvraj, Savalia, Denish, Khetan, Prakash, Sinha, Dhananjay, R, Niranjan, K, Srinivas, Pazos, Fabiola, Gacutan-Liwag, Aretha, Duszynska, Malgorzata, Antkowiak-Piatyszek, Karolina, Konieczny, Grzegorz, Sidorowicz-Bialynicka, Anna, Ciesiolkiewicz-Wojcik, Agnieszka, Dwojak, Marek, Szymkowiak, Katarzyna, Gorczyca-Siudak, Daria, Janik-Palazzolo, Marzena, Siudak, Lukasz, Opiela, Jaroslaw, Iwanow, Dariusz, Solkiewicz, Monika, Sipinska-Surzynska, Malgorzata, Olszanecka - Glinianowicz, Magdalena, Rozmilowska, Izabela, Trokis, Julian, Prozesky, Hans, Burgess, Lesley, Cyster, Henry, Jordaan, Jurie, Mohamed, Hawa, Naude, Christina, Sitsila, Thembie, Mehta, Arvind, Mocherla, Bharat, Lee, Sungchun, Boren, Kenneth, Rudolph, Lance, Benjamin, Sabrina, Sugimoto, Danny, Hammoud, Jamal, Bakleh, Muhammad, Hashish, Yaseen, Da Costa, Jonathan, Gold, Marina, Majul, Claudio, Buscema, Juan, Gatto, Maria, Lombardi, Facundo, Paez, Olga, Puleio, Pablo, Alvarisqueta, Andrés, Pajon, Vanessa, Suarez, Gabriel, Hernandez Gauna, Adrian, Pereyra, Alejandro, Reig, Moira, Gelersztein, Elizabeth, Campestri, Gina, Gonzalez Santos, Maria, Sambresqui, Julieta, Catalano, Gustavo, Igarzabal, Cecilia, Vallejos, Augusto, Escobari, Claudio, Marchetto, Rocio, Chahin, Mariano, Aguilera, Andrea, Comes, Ana, Rodriguez Segade, Silvia, Baccaro, Claudia, Larrieu Lacoste, María Verónica, Saurral, Ruben, Cristino, Alberto, Dran, Dario, Koretzky, Martin, Ponti, Juan, Porto, Alejandro, Tenaglia, Yasmin, Maldonado, Natacha, Bertollo, Natalia, Van Perdeck, Verónica, Lopau, Kai, Wanner, Christoph, Berfelo, Florieke, Contzen, Christel, Arbi, Abdulwahab, Lee-Barkey, Young Hee, Maciejewska, Aleksandra, Arelin, Katrin, Haller, Hermann, Kaufeld, Jessica, Schmidt-Ott, Kai, Heinrichs, Sven, Krüger, Thilo, Gebauer, Chris, Paliege, Alexander, Henkel, Elena, Axthelm, Christoph, Derwahl, Karl-Michael, Trevisan, Roberto, Bellante, Rosalia, Borrella, Nicolò, Corsi, Anna, Gesualdo, Loreto, Ardillo, Teodora, Ficarella, Maria, Fikry, Sameh, Mazza, Giuseppe, Poirier, Lysane, Bajaj, Harpreet, Hatziagelaki, Erifili, Katopodis, Sokratis, Katsoudas, Spiros, Yamaura, Shuichi, Shikano, Tsutomu, Tosaki, Takahiro, Miho, Otoya, Tachibana, Naoki, Yumita, Wataru, Kado, Hiroshi, Villarreal Martinez, Jesus, Soto Miranda, Ernesto, Gonzalez Rodriguez, David, Panelo, Araceli, Santos, Telma, Martins, Ana, Mateus, Catarina, Teixeira e Costa, Fernando, Barreto, Sara, Silva Costa, Joana, Ferrer, Francisco, Silva, Joana, Awad, Ahmed, Khaleel, Shatha, Lustig, Ryan, Maharjan, Gajendra, Moya, Jaynier, Johnsingh, Amit, Acosta, Idalia, Newman, George, Buckle, Anita, and Hendon, Kendra

Published
2024
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43. Accurate cancer phenotype prediction with AKLIMATE, a stacked kernel learner integrating multimodal genomic data and pathway knowledge.

Author

Uzunangelov, Vladislav, Wong, Christopher K, and Stuart, Joshua M

Subjects
Bioinformatics, Mathematical Sciences, Biological Sciences, Information and Computing Sciences
Abstract

Advancements in sequencing have led to the proliferation of multi-omic profiles of human cells under different conditions and perturbations. In addition, many databases have amassed information about pathways and gene "signatures"-patterns of gene expression associated with specific cellular and phenotypic contexts. An important current challenge in systems biology is to leverage such knowledge about gene coordination to maximize the predictive power and generalization of models applied to high-throughput datasets. However, few such integrative approaches exist that also provide interpretable results quantifying the importance of individual genes and pathways to model accuracy. We introduce AKLIMATE, a first kernel-based stacked learner that seamlessly incorporates multi-omics feature data with prior information in the form of pathways for either regression or classification tasks. AKLIMATE uses a novel multiple-kernel learning framework where individual kernels capture the prediction propensities recorded in random forests, each built from a specific pathway gene set that integrates all omics data for its member genes. AKLIMATE has comparable or improved performance relative to state-of-the-art methods on diverse phenotype learning tasks, including predicting microsatellite instability in endometrial and colorectal cancer, survival in breast cancer, and cell line response to gene knockdowns. We show how AKLIMATE is able to connect feature data across data platforms through their common pathways to identify examples of several known and novel contributors of cancer and synthetic lethality.

Published
2021

44. Effects of Empagliflozin on Fluid Overload, Weight, and Blood Pressure in CKD

Author

Mayne, Kaitlin J., Staplin, Natalie, Keane, David F., Wanner, Christoph, Brenner, Susanne, Cejka, Vladimir, Stegbauer, Johannes, Judge, Parminder K., Preiss, David, Emberson, Jonathan, Trinca, Daniele, Dayanandan, Rejive, Lee, Ryonfa, Nolan, John, Omata, Akiko, Green, Jennifer B., Cherney, David Z.I., Hooi, Lai Seong, Pontremoli, Roberto, Tuttle, Katherine R., Lees, Jennifer S., Mark, Patrick B., Davies, Simon J., Hauske, Sibylle J., Steubl, Dominik, Brückmann, Martina, Landray, Martin J., Baigent, Colin, Haynes, Richard, Herrington, William G., Baigent, Colin, Landray, Martin J., Wanner, Christoph, Herrington, William G., Haynes, Richard, Green, Jennifer B., Hauske, Sibylle J., Brueckmann, Martina, Hopley, Mark, von-Eynatten, Maximillian, George, Jyothis, Brenner, Susanne, Cheung, Alfred K., Preiss, David, Liu, Zhi-Hong, Li, Jing, Hooi, Laiseong, Liu, Wen, Kadowaki, Takashi, Nangaku, Masaomi, Levin, Adeera, Cherney, David, Pontremoli, Roberto, Maggioni, Aldo P., Staplin, Natalie, Emberson, Jonathan, Hantel, Stefan, Goto, Shinya, Deo, Rajat, Tuttle, Katherine R., Hill, Michael, Judge, Parminder, Mayne, Kaitlin J., Ng, Sarah Y.A., Rossello, Xavier, Sammons, Emily, Zhu, Doreen, Sandercock, Peter, Bilous, Rudolf, Herzog, Charles, Whelton, Paul, Wittes, Janet, Bennett, Derrick, Achiri, Patricia, Ambrose, Chrissie, Badin, Cristina, Barton, Jill, Brown, Richard, Burke, Andy, Butler, Sebastian, Dayanandan, Rejive, Donaldson, Pia, Dykas, Robert, Fletcher, Lucy, Frederick, Kate, Kingston, Hannah, Gray, Mo, Harding, Emily, Hashimoto, Akiko, Howie, Lyn, Hurley, Susan, Lee, Ryonfa, Luker, Nik, Murphy, Kevin, Nakahara, Mariko, Nolan, John, Nunn, Michelle, Mulligan, Sorcha, Omata, Akiko, Pickworth, Sandra, Qiao, YanRu, Shah, Shraddha, Taylor, Karen, Timadjer, Alison, Willett, Monique, Wincott, Liz, Yan, Qin, Yu, Hui, Bowman, Louise, Chen, Fang, Clarke, Robert, Goonasekera, Michelle, Haynes, Richard, Herrington, William G., Judge, Parminder, Karsan, Waseem, Mafham, Marion, Mayne, Kaitlin J., Ng, Sarah Y. A., Preiss, David, Reith, Christina, Sammons, Emily, Zayed, Mohammed, Zhu, Doreen, Ellison, Ritva, Moys, Rowan, Stevens, Will, Verdel, Kevin, Wallendszus, Karl, Bowler, Chris, Brewer, Anna, Measor, Andy, Cui, Guanguo, Daniels, Charles, Field, Angela, Goodenough, Bob, Lawson, Ashley, Mostefai, Youcef, Radhakrishnan, Dheeptha, Syed, Samee, Xia, Shuang, Adewuyi-Dalton, Ruth, Arnold, Thomas, Beneat, Anne-Marie, Bhatt, Anoushka, Bird, Chloe, Breach, Andrew, Brown, Laura, Caple, Mark, Chavagnon, Tatyana, Chung, Karen, Clark, Sarah, Condurache, Luminita, Eichstadt, Katarzyna, Obrero, Marta Espino, Forest, Scarlett, French, Helen, Goodwin, Nick, Gordon, Andrew, Gordon, Joanne, Guest, Cat, Harding, Tina, Hill, Michael, Hozak, Michal, Lacey, Matthew, MacLean, David, Messinger, Louise, Moffat, Stewart, Radley, Martin, Shenton, Claire, Tipper, Sarah, Tyler, Jon, Weaving, Lesley, Wheeler, James, Williams, Elissa, Williams, Tim, Woodhouse, Hamish, Chamberlain, Angela, Chambers, Jo, Davies, Joanne, Donaldson, Denise, Faria-Shayler, Pati, Fleming-Brown, Denise, Ingell, Jennifer, Knott, Carol, Liew, Anna, Lochhead, Helen, Meek, Juliette, Rodriguez-Bachiller, Isabel, Wilson, Andrea, Zettergren, Patrick, AitSadi, Rach, Barton, Ian, Baxter, Alex, Bu, Yonghong, Danel, Lukasz, Grotjahn, Sonja, Kurien, Rijo, Lay, Michael, Maskill, Archie, Murawska, Aleksandra, Raff, Rachel, Young, Allen, Baigent, Colin, Haynes, Richard, Herrington, William G., Landray, Martin J., Preiss, David, Emberson, Jonathan, Sardell, Rebecca, Staplin, Natalie, Wanner, Christoph, Brenner, Susanne, Cejka, Vladimir, Fajardo-Moser, Marcela, Hartner, Christian, Poehler, Doris, Renner, Janina, Scheidemantel, Franziska, Haynes, Richard, Preiss, David, Herrington, William G., Judge, Parminder, Zhu, Doreen, Ng, Sarah Y. 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Published
2024
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48. Whole-genome characterization of lung adenocarcinomas lacking the RTK/RAS/RAF pathway.

Author

Carrot-Zhang, Jian, Yao, Xiaotong, Devarakonda, Siddhartha, Deshpande, Aditya, Damrauer, Jeffrey S, Silva, Tiago Chedraoui, Wong, Christopher K, Choi, Hyo Young, Felau, Ina, Robertson, A Gordon, Castro, Mauro AA, Bao, Lisui, Rheinbay, Esther, Liu, Eric Minwei, Trieu, Tuan, Haan, David, Yau, Christina, Hinoue, Toshinori, Liu, Yuexin, Shapira, Ofer, Kumar, Kiran, Mungall, Karen L, Zhang, Hailei, Lee, Jake June-Koo, Berger, Ashton, Gao, Galen F, Zhitomirsky, Binyamin, Liang, Wen-Wei, Zhou, Meng, Moorthi, Sitapriya, Berger, Alice H, Collisson, Eric A, Zody, Michael C, Ding, Li, Cherniack, Andrew D, Getz, Gad, Elemento, Olivier, Benz, Christopher C, Stuart, Josh, Zenklusen, JC, Beroukhim, Rameen, Chang, Jason C, Campbell, Joshua D, Hayes, D Neil, Yang, Lixing, Laird, Peter W, Weinstein, John N, Kwiatkowski, David J, Tsao, Ming S, Travis, William D, Khurana, Ekta, Berman, Benjamin P, Hoadley, Katherine A, Robine, Nicolas, TCGA Research Network, Meyerson, Matthew, Govindan, Ramaswamy, and Imielinski, Marcin

Subjects
TCGA Research Network, TCGA, driver, genome analysis, lung adenocarcinoma, noncoding, oncogene, precision oncology, structural variation, tumor suppressor, whole genome sequencing, Biochemistry and Cell Biology, Medical Physiology
Abstract

RTK/RAS/RAF pathway alterations (RPAs) are a hallmark of lung adenocarcinoma (LUAD). In this study, we use whole-genome sequencing (WGS) of 85 cases found to be RPA(-) by previous studies from The Cancer Genome Atlas (TCGA) to characterize the minority of LUADs lacking apparent alterations in this pathway. We show that WGS analysis uncovers RPA(+) in 28 (33%) of the 85 samples. Among the remaining 57 cases, we observe focal deletions targeting the promoter or transcription start site of STK11 (n = 7) or KEAP1 (n = 3), and promoter mutations associated with the increased expression of ILF2 (n = 6). We also identify complex structural variations associated with high-level copy number amplifications. Moreover, an enrichment of focal deletions is found in TP53 mutant cases. Our results indicate that RPA(-) cases demonstrate tumor suppressor deletions and genome instability, but lack unique or recurrent genetic lesions compensating for the lack of RPAs. Larger WGS studies of RPA(-) cases are required to understand this important LUAD subset.

Published
2021

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