arXiv subjects

Balasubramanian Narasimhan

Publications and source records attributed to Balasubramanian Narasimhan.

11 recordsLinked to original sources

arXiv2026

Fully Homomorphic Encryption for Statistical Modeling

Fully homomorphic encryption allows arithmetic to be carried out on encrypted values, so that a party performing a computation need not see the data it operates on. This is useful wherever collaborating parties or sites cannot share data records or computed summaries yet need to do a joint analysis. We demonstrate the protocols needed to perform such analyses reproducibly via two packages in R, a platform widely used for applied statistics. The first, openfhe.R, is an interface to the OpenFHE C++ library, which exposes exact integer arithmetic (BFV, BGV), approximate real-valued arithmetic (CKKS), Boolean circuits, and multiparty key generation. The second is homomorpheR, which builds a small set of master/worker primitives for multi-party protocols on top of the first. Together, the two let an ordinary R statistical routine compose with an encrypted-arithmetic layer at the function-value boundary, provided the quantity crossing that boundary decomposes as a sum over sites. Two validation studies are presented: distributed stratified Cox regression, where stats4::mle() converges through an encrypted channel, and federated Cox-lasso via convex optimization using consensus ADMM, where the cross-site update is the only encrypted step. We also discuss federated similarity retrieval and two-party prediction. Throughout, the parties are assumed honest-but-curious, and threshold key generation removes the assumption that any single party holds a usable secret key.

cs.CR↗

arXiv2026

VISTA Architect: A graph database-oriented health AI system demonstrated in multidisciplinary tumor boards

We introduce VISTA Architect, a database-oriented AI architecture for integrating large language models (LLMs) with longitudinal electronic health records (EHRs). At ingestion, it transforms complex clinical documentation into a persistent, provenance-linked knowledge graph, eliminating repeated reprocessing of raw records at query time. The architecture has two layers: a source-faithful MEDS Graph preserving granular EHR structure with full provenance, and a clinically abstracted Timeline Object Architecture (TOA) that uses graph-guided LLM extraction to synthesize a concise timeline of deduplicated, temporally coherent clinical events. This addresses key limitations of direct long-context prompting and retrieval-augmented generation (RAG), which often miss temporal relationships and incur high cost and latency from repeated raw-text processing. By precomputing clinical synthesis once, downstream queries access an organized patient state and traverse to source documentation only when detailed verification is needed. We demonstrate the system in multidisciplinary thoracic oncology tumor boards at Stanford Medicine, where precise reconstruction of patient histories is critical. Across 1,180 patients, VISTA Architect achieved 96.4% accuracy (mean 9.75/10) on 15 tumor board-salient variables (17,700 evaluations; 95% CI 96.1-96.7%), surpassing a matched BM25 RAG baseline and recent benchmarks for LLM-based clinical extraction. An agentic interface reduced preparation for a 30-patient held-out cohort to about 2.2 minutes without sacrificing accuracy. While configured here for thoracic oncology, the modular design adapts to other specialties through customizable event definitions, episode structures, and agentic tools; validation beyond thoracic oncology remains future work.

cs.AI↗

arXiv2026

Univariate-Guided Sparse Regression for Biobank-Scale High-Dimensional Omics Data

We present a scalable framework for computing polygenic risk scores (PRS) in high-dimensional genomic settings using the recently introduced Univariate-Guided Sparse Regression (uniLasso). UniLasso is a two-stage penalized regression procedure that leverages univariate coefficients and magnitudes to stabilize feature selection and enhance interpretability. Building on its theoretical and empirical advantages, we adapt uniLasso for application to the UK Biobank, a population-based repository comprising over one million genetic variants measured on hundreds of thousands of individuals from the United Kingdom. We further extend the framework to incorporate external summary statistics to increase predictive accuracy. Our results demonstrate that uniLasso attains predictive performance comparable to standard Lasso while selecting substantially fewer variants, yielding sparser and more interpretable models. Moreover, it exhibits superior performance in estimating PRS relative to its competitors, such as PRS-CS. Integrating external scores further improves prediction while maintaining sparsity.

stat.ME↗

arXiv2024

Pretraining and the Lasso

Pretraining is a popular and powerful paradigm in machine learning to pass information from one model to another. As an example, suppose one has a modest-sized dataset of images of cats and dogs, and plans to fit a deep neural network to classify them from the pixel features. With pretraining, we start with a neural network trained on a large corpus of images, consisting of not just cats and dogs but hundreds of other image types. Then we fix all of the network weights except for the top layer(s) (which makes the final classification) and train (or "fine tune") those weights on our dataset. This often results in dramatically better performance than the network trained solely on our smaller dataset. In this paper, we ask the question "Can pretraining help the lasso?". We develop a framework for the lasso in which a model is fit to a large dataset, and then fine-tuned using a smaller dataset. This latter dataset can be a subset of the original dataset, or it can be a dataset with a different but related outcome. This framework has a wide variety of applications, including stratified models, multinomial responses, multi-response models, conditional average treatment estimation and even gradient boosting. In the stratified model setting, the pretrained lasso pipeline estimates the coefficients common to all groups at the first stage, and then estimates the group-specific coefficients at the second "fine-tuning" stage. We show that under appropriate assumptions, the support recovery rate of the common coefficients is superior to that of the usual lasso trained only on individual groups. This separate identification of common and individual coefficients can also be useful for scientific understanding.

stat.ME↗

arXiv2022

Cooperative learning for multiview analysis

We propose a new method for supervised learning with multiple sets of features ("views"). The multiview problem is especially important in biology and medicine, where "-omics" data such as genomics, proteomics and radiomics are measured on a common set of samples. Cooperative learning combines the usual squared error loss of predictions with an "agreement" penalty to encourage the predictions from different data views to agree. By varying the weight of the agreement penalty, we get a continuum of solutions that include the well-known early and late fusion approaches. Cooperative learning chooses the degree of agreement (or fusion) in an adaptive manner, using a validation set or cross-validation to estimate test set prediction error. One version of our fitting procedure is modular, where one can choose different fitting mechanisms (e.g. lasso, random forests, boosting, neural networks) appropriate for different data views. In the setting of cooperative regularized linear regression, the method combines the lasso penalty with the agreement penalty, yielding feature sparsity. The method can be especially powerful when the different data views share some underlying relationship in their signals that can be exploited to boost the signals. We show that cooperative learning achieves higher predictive accuracy on simulated data and a real multiomics example of labor onset prediction. Leveraging aligned signals and allowing flexible fitting mechanisms for different modalities, cooperative learning offers a powerful approach to multiomics data fusion.

stat.ME↗

arXiv2021

Elastic Net Regularization Paths for All Generalized Linear Models

The lasso and elastic net are popular regularized regression models for supervised learning. Friedman, Hastie, and Tibshirani (2010) introduced a computationally efficient algorithm for computing the elastic net regularization path for ordinary least squares regression, logistic regression and multinomial logistic regression, while Simon, Friedman, Hastie, and Tibshirani (2011) extended this work to Cox models for right-censored data. We further extend the reach of the elastic net-regularized regression to all generalized linear model families, Cox models with (start, stop] data and strata, and a simplified version of the relaxed lasso. We also discuss convenient utility functions for measuring the performance of these fitted models.

stat.CO↗

arXiv2020

CVXR: An R Package for Disciplined Convex Optimization

CVXR is an R package that provides an object-oriented modeling language for convex optimization, similar to CVX, CVXPY, YALMIP, and Convex.jl. It allows the user to formulate convex optimization problems in a natural mathematical syntax rather than the restrictive form required by most solvers. The user specifies an objective and set of constraints by combining constants, variables, and parameters using a library of functions with known mathematical properties. CVXR then applies signed disciplined convex programming (DCP) to verify the problem's convexity. Once verified, the problem is converted into standard conic form using graph implementations and passed to a cone solver such as ECOS or SCS. We demonstrate CVXR's modeling framework with several applications.

stat.CO↗

arXiv2018

A Scalable Discrete-Time Survival Model for Neural Networks

There is currently great interest in applying neural networks to prediction tasks in medicine. It is important for predictive models to be able to use survival data, where each patient has a known follow-up time and event/censoring indicator. This avoids information loss when training the model and enables generation of predicted survival curves. In this paper, we describe a discrete-time survival model that is designed to be used with neural networks, which we refer to as Nnet-survival. The model is trained with the maximum likelihood method using minibatch stochastic gradient descent (SGD). The use of SGD enables rapid convergence and application to large datasets that do not fit in memory. The model is flexible, so that the baseline hazard rate and the effect of the input data on hazard probability can vary with follow-up time. It has been implemented in the Keras deep learning framework, and source code for the model and several examples is available online. We demonstrate the performance of the model on both simulated and real data and compare it to existing models Cox-nnet and Deepsurv.

stat.ML↗

arXiv2018

Imputation of mixed data with multilevel singular value decomposition

Statistical analysis of large data sets offers new opportunities to better understand many processes. Yet, data accumulation often implies relaxing acquisition procedures or compounding diverse sources. As a consequence, such data sets often contain mixed data, i.e. both quantitative and qualitative and many missing values. Furthermore, aggregated data present a natural \textit{multilevel} structure, where individuals or samples are nested within different sites, such as countries or hospitals. Imputation of multilevel data has therefore drawn some attention recently, but current solutions are not designed to handle mixed data, and suffer from important drawbacks such as their computational cost. In this article, we propose a single imputation method for multilevel data, which can be used to complete either quantitative, categorical or mixed data. The method is based on multilevel singular value decomposition (SVD), which consists in decomposing the variability of the data into two components, the between and within groups variability, and performing SVD on both parts. We show on a simulation study that in comparison to competitors, the method has the great advantages of handling data sets of various size, and being computationally faster. Furthermore, it is the first so far to handle mixed data. We apply the method to impute a medical data set resulting from the aggregation of several data sets coming from different hospitals. This application falls in the framework of a larger project on Trauma patients. To overcome obstacles associated to the aggregation of medical data, we turn to distributed computation. The method is implemented in an R package.

stat.AP↗

arXiv2017

Software for Distributed Computation on Medical Databases: A Demonstration Project

Bringing together the information latent in distributed medical databases promises to personalize medical care by enabling reliable, stable modeling of outcomes with rich feature sets (including patient characteristics and treatments received). However, there are barriers to aggregation of medical data, due to lack of standardization of ontologies, privacy concerns, proprietary attitudes toward data, and a reluctance to give up control over end use. Aggregation of data is not always necessary for model fitting. In models based on maximizing a likelihood, the computations can be distributed, with aggregation limited to the intermediate results of calculations on local data, rather than raw data. Distributed fitting is also possible for singular value decomposition. There has been work on the technical aspects of shared computation for particular applications, but little has been published on the software needed to support the "social networking" aspect of shared computing, to reduce the barriers to collaboration. We describe a set of software tools that allow the rapid assembly of a collaborative computational project, based on the flexible and extensible R statistical software and other open source packages, that can work across a heterogeneous collection of database environments, with full transparency to allow local officials concerned with privacy protections to validate the safety of the method. We describe the principles, architecture, and successful test results for the site-stratified Cox model and rank-k Singular Value Decomposition (SVD).

stat.CO↗

arXiv2014

A New Approach to Designing Phase I-II Cancer Trials for Cytotoxic Chemotherapies

Recently there has been much work on early phase cancer designs that incorporate both toxicity and efficacy data, called Phase I-II designs because they combine elements of both phases. However, they do not explicitly address the Phase II hypothesis test of $H_0: p\le p_0$, where $p$ is the probability of efficacy at the estimated maximum tolerated dose (MTD) $\widehatη$ from Phase I and $p_0$ is the baseline efficacy rate. Standard practice for Phase II remains to treat $p$ as a fixed, unknown parameter and to use Simon's 2-stage design with all patients dosed at $\widehatη$. We propose a Phase I-II design that addresses the uncertainty in the estimate $p=p(\widehatη)$ in $H_0$ by using sequential generalized likelihood theory. Combining this with a Phase I design that incorporates efficacy data, the Phase I-II design provides a common framework that can be used all the way from the first dose of Phase I through the final accept/reject decision about $H_0$ at the end of Phase II, utilizing both toxicity and efficacy data throughout. Efficient group sequential testing is used in Phase II that allows for early stopping to show treatment effect or futility. The proposed Phase I-II design thus removes the artificial barrier between Phase I and Phase II, and fulfills the objectives of searching for the MTD and testing if the treatment has an acceptable response rate to enter into a Phase III trial.

stat.ME↗