Searcharxiv⌕ Search

arXiv subjects

Rajanikanth Vadigepalli

Publications and source records attributed to Rajanikanth Vadigepalli.

2 recordsLinked to original sources

From FAIR to CURE: Guidelines for Computational Models of Biological Systems

Guidelines for managing scientific data have been established under the FAIR principles requiring that data be Findable, Accessible, Interoperable, and Reusable. In many scientific disciplines, especially computational biology, both data and models are key to progress. For this reason, and recognizing that such models are a very special type of 'data', we argue that computational models, especially mechanistic models prevalent in medicine, physiology and systems biology, deserve a complementary set of guidelines. We propose the CURE principles, emphasizing that models should be Credible, Understandable, Reproducible, and Extensible. We delve into each principle, discussing verification, validation, and uncertainty quantification for model credibility; the clarity of model descriptions and annotations for understandability; adherence to standards and open science practices for reproducibility; and the use of open standards and modular code for extensibility and reuse. We outline recommended and baseline requirements for each aspect of CURE, aiming to enhance the impact and trustworthiness of computational models, particularly in biomedical applications where credibility is paramount. Our perspective underscores the need for a more disciplined approach to modeling, aligning with emerging trends such as Digital Twins and emphasizing the importance of data and modeling standards for interoperability and reuse. Finally, we emphasize that given the non-trivial effort required to implement the guidelines, the community moves to automate as many of the guidelines as possible.

q-bio.OT↗

A windowed local fdr estimator providing higher resolution and robust thresholds

Motivation: In microarray analysis, special consideration must be given to the issues of multiple statistical tests and typically p-values are adjusted to control family-wise error rate (FWER) or false discovery rate (FDR). FDR metrics have been suggested for controlling false positives, however, genes with p-values close to the threshold typically have a higher chance of being false positives than genes with very low p-values. The local FDR (fdr) metric gives the number of false positives in the vicinity of a test statistic. We propose a new fdr estimator that uses windows instead of binsand define heuristics that use the fluctuations in the estimator to determine robust thresholds for classifying differential expression. Results: Our fdr approach estimates the false discovery rate within a window of p-values. We present heuristics that derive robust fdr thresholds such that a significant change in the fdr threshold yields a small change in the number of rejected hypotheses. We compare these thresholds with thresholds from other approaches using two simulated datasets and one cancer microarray dataset. In the latter, our estimator finds two robust thresholds. Since our fdr estimator is an extension of the FDR metric, it can be used with many FDR estimation methods. Availability: An R function implementing the proposed estimator is available at http://www.dbi.tju.edu/dbi/tools/fdr Contact: james.schwaber@jefferson.edu Supplementary Information: Supplementary figures and code are available at http://www.dbi.tju.edu/dbi/tools/fdr

q-bio.QM↗