Search bioRxiv⌕ Search

Biology subjects

Shetab Boushehri, S.

Publications and source records attributed to Shetab Boushehri, S..

4 recordsLinked to original sources

scifAI: Explainable machine learning for profiling the immunological synapse and functional characterization of therapeutic antibodies

Therapeutic antibodies are widely used to treat severe diseases. Most of them alter immune cells and act within the immunological synapse; an essential cell-to-cell interaction to direct the humoral immune response. Although many antibody designs are generated and evaluated, a high-throughput tool for systematic antibody characterization and prediction of function is lacking. Here, we introduce the first comprehensive open-source framework, scifAI (single-cell imaging flow cytometry AI), for preprocessing, feature engineering and explainable, predictive machine learning on imaging flow cytometry (IFC) data. Additionally, we generate the largest publicly available IFC data set of the human immunological synapse containing over 2.8 million images. Using scifAI, we analyze class frequency- and morphological changes under different immune stimulation. T cell cytokine production across multiple donors and therapeutic antibodies is quantitatively predicted in vitro, linking morphological features with function and demonstrating the potential to significantly impact antibody design. scifAI is universally applicable to IFC data. Given its modular architecture it is straightforward to incorporate into existing workflows and analysis pipelines, e.g. for rapid antibody screening and functional characterization.

bioinformatics↗

Label-free imaging of 3D pluripotent stem cell differentiation dynamics on chip

The dynamic chemical and architectural microenvironments of 3D stem cell cultures can be controlled by integration into a microfluidic chip. Massive parallelized 3D stem cell cultures for engineering in vitro human cell types require new imaging methods with high time and spatial resolution to fully exploit technological advances in cell culture. Here, we introduce a label-free deep learning method called Bright2Nuc to predict in silico nuclear staining in 3D from bright-field images obtained using traditional confocal microscopy. Bright2Nuc was trained and applied to several hundred 3D human induced pluripotent stem cell cultures differentiating towards definitive endoderm on a microfluidic platform. Combined with existing image analysis tools, Bright2Nuc segmented individual nuclei from bright-field images, quantified their morphological properties, predicted stem cell differentiation state, and tracked the cells over time. Our methods are available in an open-source pipeline that enables researchers to upscale 3D cell phenotyping in stem cell culture.

bioinformatics↗

Annotation-efficient classification combining active learning, pre-training and semi-supervised learning for biomedical images

Deep learning based classification of biomedical images requires manual annotation by experts, which is time-consuming and expensive. Incomplete-supervision approaches including active learning, pre-training and semi-supervised learning address this issue and aim to increase classification performance with a limited number of annotated images. Up to now, these approaches have been mostly benchmarked on natural image datasets, where image complexity and class balance typically differ considerably from biomedical classification tasks. In addition, it is not clear how to combine them to improve classification performance on biomedical image data. We thus performed an extensive grid search combining seven active learning algorithms, three pre-training methods and two training strategies as well as respective baselines (random sampling, random initialization, and supervised learning). For four biomedical datasets, we started training with 1% of labeled data and increased it by 5% iteratively, using 4-fold cross-validation in each cycle. We found that the contribution of pre-training and semi-supervised learning can reach up to 25% macro F1-score in each cycle. In contrast, the state-of-the-art active learning algorithms contribute less than 5% to macro F1-score in each cycle. Based on performance, implementation ease and computation requirements, we recommend the combination of BADGE active learning, ImageNet-weights pre-training, and pseudo-labeling as training strategy, which reached over 90% of fully supervised results with only 25% of annotated data for three out of four datasets. We believe that our study is an important step towards annotation and resource efficient model training for biomedical classification challenges.

bioinformatics↗

InstantDL - An easy-to-use deep learning pipeline for image segmentation and classification

MotivationDeep learning contributes to uncovering and understanding molecular and cellular processes with highly performant image computing algorithms. Convolutional neural networks have become the state-of-the-art tool to provide accurate, consistent and fast data processing. However, published algorithms mostly solve only one specific problem and they often require expert skills and a considerable computer science and machine learning background for application. ResultsWe have thus developed a deep learning pipeline called InstantDL for four common image processing tasks: semantic segmentation, instance segmentation, pixel-wise regression and classification. InstantDL enables experts and non-experts to apply state-of-the-art deep learning algorithms to biomedical image data with minimal effort. To make the pipeline robust, we have automated and standardized workflows and extensively tested it in different scenarios. Moreover, it allows to assess the uncertainty of predictions. We have benchmarked InstantDL on seven publicly available datasets achieving competitive performance without any parameter tuning. For customization of the pipeline to specific tasks, all code is easily accessible. Availability and ImplementationInstantDL is available under the terms of MIT licence. It can be found on GitHub: https://github.com/marrlab/InstantDL Contactcarsten.marr@helmholtz-muenchen.de

bioinformatics↗