Convolutional Neural Networks for Automatic Detection of Intact Adenovirus from TEM Imaging with Debris, Broken and Artefacts Particles
This provides a tool for manufacturers of virus-based gene therapy products to monitor particle purity, though it is an incremental improvement using existing methods on new data.
The researchers tackled the problem of automatically detecting intact adenoviruses in TEM images cluttered with debris and artifacts, achieving high true positive detection rates with low false positives and negatives.
Regular monitoring of the primary particles and purity profiles of a drug product during development and manufacturing processes is essential for manufacturers to avoid product variability and contamination. Transmission electron microscopy (TEM) imaging helps manufacturers predict how changes affect particle characteristics and purity for virus-based gene therapy vector products and intermediates. Since intact particles can characterize efficacious products, it is beneficial to automate the detection of intact adenovirus against a non-intact-viral background mixed with debris, broken, and artefact particles. In the presence of such particles, detecting intact adenoviruses becomes more challenging. To overcome the challenge, due to such a presence, we developed a software tool for semi-automatic annotation and segmentation of adenoviruses and a software tool for automatic segmentation and detection of intact adenoviruses in TEM imaging systems. The developed semi-automatic tool exploited conventional image analysis techniques while the automatic tool was built based on convolutional neural networks and image analysis techniques. Our quantitative and qualitative evaluations showed outstanding true positive detection rates compared to false positive and negative rates where adenoviruses were nicely detected without mistaking them for real debris, broken adenoviruses, and/or staining artefacts.