/SiteLocalization

Binding site localization on non-homogeneous cell surfaces using topological image averaging

Primary LanguageJulia

SiteLocalization

Binding site localization on non-homogeneous cell surfaces using topological image averaging

Usage

Usage Example

usage: run.jl [--pixelsize PIXELSIZE] [--shiftwindow SHIFTWINDOW]
              [--maxpeakswindow MAXPEAKSWINDOW]
              [--iterations ITERATIONS] [--psf_sigma PSF_SIGMA]
              [--highp HIGHP] [--lowp LOWP] [--blur BLUR]
              [--mindistance MINDISTANCE] [--margin MARGIN]
              [--votingthreshold VOTINGTHRESHOLD] [--rmin RMIN]
              [--rmax RMAX] [--pxmult PXMULT] [--al-shifty AL-SHIFTY]
              [--al-shiftx AL-SHIFTX]
              [--first-snr-limit FIRST-SNR-LIMIT]
              [--snr-ratio-limit SNR-RATIO-LIMIT] [--limit-outside]
              [--maxdist MAXDIST] [--debug-plots]
              [--enable-sigma-norm] [--name NAME] [-h] images...

positional arguments:
  images                images to analyze

optional arguments:
  --pixelsize PIXELSIZE
                        image pixel size in nanometers (type: Float64,
                        default: 20.5333)
  --shiftwindow SHIFTWINDOW
                        for sliding average of peak alignment, 0 if
                        only aligning max of peaks (type: Int64,
                        default: 7)
  --maxpeakswindow MAXPEAKSWINDOW
                        sliding average for sum of several circles
                        (type: Int64, default: 0)
  --iterations ITERATIONS
                        RL iterations (type: Int64, default: 0)
  --psf_sigma PSF_SIGMA
                        Measured sigma of psf, for Richardsson Lucy
                        deconvolution (type: Int64, default: 4)
  --highp HIGHP         For canny edge detection and circle hough
                        transform, in percentile (type: Float64,
                        default: 99.8)
  --lowp LOWP           For canny edge detection and circle hough
                        transform, in percentile (type: Float64,
                        default: 95.0)
  --blur BLUR           blur for segmentation (type: Float64, default:
                        3.5)
  --mindistance MINDISTANCE
                        in pixels, the minimum distance between two
                        circle centers (type: Int64, default: 50)
  --margin MARGIN       fitted circle radius margin (type: Int64,
                        default: 20)
  --votingthreshold VOTINGTHRESHOLD
                        sensitivity of circle detection in pixels
                        (type: Int64, default: 20)
  --rmin RMIN           fitted circle minimum radius (type: Int64,
                        default: 36)
  --rmax RMAX           fitted circle maximum radius (type: Int64,
                        default: 44)
  --pxmult PXMULT       pixel interpolation (type: Float64, default:
                        2.0)
  --al-shifty AL-SHIFTY
                        adjust for measured chromatic aberration
                        (type: Float64, default: -0.63)
  --al-shiftx AL-SHIFTX
                        adjust for measured chromatic aberration
                        (type: Float64, default: -1.35)
  --first-snr-limit FIRST-SNR-LIMIT
                        SNR limit for first frame for analyzing a time
                        sequence (type: Float64, default: 0.0)
  --snr-ratio-limit SNR-RATIO-LIMIT
                        SNR limit in terms of ratio to SNR of first
                        frame at which to stop analyzing a time
                        sequence (type: Float64, default: 0.3)
  --limit-outside       limit search for peaks to outside of reference
                        channel
  --maxdist MAXDIST     maximum distance from reference channel within
                        which to search for peaks (type: Int64,
                        default: 0)
  --debug-plots         enable saving of plots and images for
                        debugging purposes
  --enable-sigma-norm   enable saving of plots and images for
                        debugging purposes
  --name NAME
  -h, --help            show this help message and exit

Abstract

Antibody binding to cell surface proteins plays a crucial role in immunity and the location of an epitope can altogether determine the immunological outcome of a host-target interaction. Techniques available today for epitope identification are costly, time-consuming, and unsuited for high-throughput analysis. Fast and efficient screening of epitope location can be useful for the development of therapeutic monoclonal antibodies and vaccines. In the present work, we have developed a method for imaging-based localization of binding sites on cellular surface proteins. The cellular morphology typically varies, and antibodies often bind in a non-homogenous manner, making traditional particle-averaging strategies challenging for accurate native antibody localization. Nanometer-scale resolution is achieved through localization in one dimension, namely the distance from a bound ligand to a reference surface, by using topological image averaging. Our results show that this method is well suited for antibody binding site measurements on native cell surface morphology.