bioRxiv Science⌕ Search
Home/Archive/bioRxiv

bioRxiv · 10.1101/029694

AOP: An R Package For Sufficient Causal Analysis in Pathway-based Screening of Drugs and Chemicals for Adversity

Lyle D Burgoon
View original source ↗Export metadata ↓

Abstract

SummaryHow can I quickly find the key events in a pathway that I need to monitor to predict that a/an beneficial/adverse event/outcome will occur? This is a key question when using signaling pathways for drug/chemical screening in pharmacology, toxicology and risk assessment. By identifying these sufficient causal key events, we have fewer events to monitor for a pathway, thereby decreasing assay costs and time, while maximizing the value of the information. I have developed the \"aop\" package which uses back-door analysis of causal networks to identify these minimal sets of key events that are sufficient for making causal predictions.\n\nAvailability and ImplementationThe source for the aop package is available online at Github at https://github.com/DataSciBurgoon/aop and can be installed using the R devtools package. The aop package runs within the R statistical environment. The package has functions that can take pathways (as directed graphs) formatted as a Cytoscape JSON file as input, or pathways can be represented as directed graphs using the R/Bioconductor \"graph\" package. The \"aop\" package has functions that can perform backdoor analysis to identify the minimal set of key events for making causal predictions.\n\nContactlyle.d.burgoon@usace.army.mil

Explore related subjects

BioinformaticsPreprint

Keep this discovery

BibTeXRIS

Lyle D Burgoon. 2015-10-23. AOP: An R Package For Sufficient Causal Analysis in Pathway-based Screening of Drugs and Chemicals for Adversity. https://doi.org/10.1101/029694

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

KEEP EXPLORING

Related preprints

bioRxiv2016

iCARE: An R Package to Build and Apply Absolute Risk Models

This report describes a R package, called the Individualized Coherent Absolute Risk Estimation (iCARE) tool, that allows researchers to build and evaluate models for absolute risk and apply them to estimate an individuals risk of developing disease during a specified time interval based on a set of user defined input parameters. An attractive feature of the software is that it gives users flexibility to update models rapidly based on new knowledge on risk factors and tailor models to different populations by specifying three input arguments: (1) a model for relative risk, (2) an age-specific disease incidence rate, (3) the distribution of risk factors for the population of interest. The tool can handle missing information on risk factors for individuals for whom risks are to be predicted using a coherent approach where all estimates are derived from a single model after appropriate model averaging. The software allows single nucleotide polymorphisms (SNPs) to be incorporated into the model using published odds ratios and allele frequencies. The validation component of the software implements the methods for evaluation of model calibration, discrimination and risk-stratification based on independent validation datasets. We provide an illustration of the utility of iCARE for building, validating and applying absolute risk models using breast cancer as an example.

Bioinformatics↗
bioRxiv2016

deSPI: efficient classification of metagenomic reads with lightweight de Bruijn graph-based reference indexing

SummaryIn metagenomic studies, fast and effective tools are on wide demand to implement taxonomy classification for upto billions of reads. Herein, we propose deSPI, a novel read classification method that classifies reads by recognizing and analyzing the matches between reads and reference with de Bruijn graph-based lightweight reference indexing. deSPI has faster speed with relatively small memory footprint, meanwhile, it can also achieve higher or similar sensitivity and accuracy.\n\nAvailabilitythe C++ source code of deSPI is available at https://github.com/hitbc/deSPI\n\nContactydwang@hit.edu.cn\n\nSupplementary informationSupplementary data are available at Bioinformatics online.

Bioinformatics↗
bioRxiv2016

De novo assembly of viral quasispecies using overlap graphs

A viral quasispecies, the ensemble of viral strains populating an infected person, can be highly diverse. For optimal assessment of virulence, pathogenesis and therapy selection, determining the haplotypes of the individual strains can play a key role. As many viruses are subject to high mutation and recombination rates, high-quality reference genomes are often not available at the time of a new disease outbreak. We present SAVAGE, a computational tool for reconstructing individual haplotypes of intrahost virus strains without the need for a high-quality reference genome. SAVAGE makes use of either FM-index based data structures or ad-hoc consensus reference sequence for constructing overlap graphs from patient sample data. In this overlap graph, nodes represent reads and/or contigs, while edges reflect that two reads/contigs, based on sound statistical considerations, represent identical haplotypic sequence. Following an iterative scheme, a new overlap assembly algorithm that is based on the enumeration of statistically well-calibrated groups of reads/contigs then efficiently reconstructs the individual haplotypes from this overlap graph. In benchmark experiments on simulated and on real deep coverage data, SAV-AGE drastically outperforms generic de novo assemblers as well as the only specialized de novo viral quasispecies assembler available so far. When run on ad-hoc consensus reference sequence, SAVAGE performs very favorably in comparison with state-of-the-art reference genome guided tools. We also apply SAVAGE on two deep coverage samples of patients infected by the Zika and the hepatitis C virus, respectively, which sheds light on the genetic structures of the respective viral quasispecies.

Bioinformatics↗