SmoothWin

SmoothWin applies soft windowing with an exponential weighting function to prioritize temporally proximate controls and reduce temporal and environmental noise when detecting genotype–phenotype associations in high-throughput phenotyping data.


Key Features:

  • Soft Windowing Methodology: Employs an exponential weighting function to create adaptive temporal windows that give maximal weight to control data collected close in time and progressively less weight to more distant data.
  • Parameter Optimization: Incorporates tests to identify optimal windowing parameters by controlling bandwidth and sharpness through adjustable parameters.
  • Reduction in False Positives: Application to International Mouse Phenotyping Consortium (IMPC) phenotype data produced approximately 10% fewer false positives across 2.5 million analyses compared to non-windowed approaches.
  • Increased Analytical Power: Reported about a 30% improvement in detection of significant P-values relative to traditional non-windowed methods.
  • Validation via Resampling: Methodological robustness is supported by validation using resampling techniques.
  • Generalizability: Applicable beyond mouse phenotyping to large-scale human phenomic projects such as UK Biobank and All of Us and other high-throughput phenotyping contexts.

Scientific Applications:

  • Genotype–Phenotype Association Analysis: Refines analysis pipelines by managing temporal variation and environmental noise to enhance precision of phenotype comparisons between mutant and control groups.
  • Large-Scale Phenomic Studies: Improves detection of phenotype–disease model links in datasets from projects such as the IMPC, UK Biobank, and All of Us.

Methodology:

Applies an exponential weighting function to linear regression models within a defined time window, optimizes bandwidth and sharpness parameters via parameter tests, and validates results using resampling techniques.

Topics

Details

License:
LGPL-2.0
Programming Languages:
R
Added:
1/9/2020
Last Updated:
11/24/2024

Operations

Publications

Haselimashhadi H, Mason JC, Munoz-Fuentes V, López-Gómez F, Babalola K, Acar EF, Kumar V, White J, Flenniken AM, King R, Straiton E, Seavitt JR, Gaspero A, Garza A, Christianson AE, Hsu C, Reynolds CL, Lanza DG, Lorenzo I, Green JR, Gallegos JJ, Bohat R, Samaco RC, Veeraragavan S, Kim JK, Miller G, Fuchs H, Garrett L, Becker L, Kang YK, Clary D, Cho SY, Tamura M, Tanaka N, Soo KD, Bezginov A, About GB, Champy M, Vasseur L, Leblanc S, Meziane H, Selloum M, Reilly PT, Spielmann N, Maier H, Gailus-Durner V, Sorg T, Hiroshi M, Yuichi O, Heaney JD, Dickinson ME, Wolfgang W, Tocchini-Valentini GP, Lloyd KCK, McKerlie C, Seong JK, Yann H, de Angelis MH, Brown SDM, Smedley D, Flicek P, Mallon A, Parkinson H, Meehan TF. Soft windowing application to improve analysis of high-throughput phenotyping data. Bioinformatics. 2019;36(5):1492-1500. doi:10.1093/bioinformatics/btz744. PMID:31591642. PMCID:PMC7115897.

PMID: 31591642
PMCID: PMC7115897
Funding: - NIH: U42 OD011174, U54 HG005348, UM1 HG006348, UM1 HG006370, UM1 OD023221, UM1OD023222 - Genome Canada and Ontario Genomics: OGI-051 & 137 - Korea Mouse Phenotyping Project: 2017M3A9D5A01052447 - Agence Nationale de la Recherche: ANR-10-IDEX-0002-02, ANR-10-INBS-07 PHENOMIN, ANR-10-LABX-0030-INRT - German Federal Ministry of Education and Research: Infrafrontier: 01KX1012 - EU Horizon2020: 653961 - Tools for Functional Annotation of the Mouse Genome: FP7-HEALTH-F4-2010-261492