Martin Weigert

Related publications (5)

MarrowQuant 2.0: A Digital Pathology Workflow Assisting Bone Marrow Evaluation in Experimental and Clinical Hematology

Giovanna Ambrosini, Olivier Burri, Mariangela Costanza, Bart Deplancke, Olaia Maria Naveiras Torres-Quiroga, Rita Sarkis, Frédérica Schyrr, Arne Seitz, Martin Weigert

2023

Event-driven acquisition for content-enriched microscopy

Juliette Griffie, Dora Mahecic, Suliana Manley, Willi Leopold Stepp, Martin Weigert, Chen Zhang

Event-driven acquisition uses neural-network-based recognition of specific biological events to trigger switching between slow and fast super-resolution imaging, enriching the capture of interesting events with high spatiotemporal resolution. A common goal of fluorescence microscopy is to collect data on specific biological events. Yet, the event-specific content that can be collected from a sample is limited, especially for rare or stochastic processes. This is due in part to photobleaching and phototoxicity, which constrain imaging speed and duration. We developed an event-driven acquisition framework, in which neural-network-based recognition of specific biological events triggers real-time control in an instant structured illumination microscope. Our setup adapts acquisitions on-the-fly by switching between a slow imaging rate while detecting the onset of events, and a fast imaging rate during their progression. Thus, we capture mitochondrial and bacterial divisions at imaging rates that match their dynamic timescales, while extending overall imaging durations. Because event-driven acquisition allows the microscope to respond specifically to complex biological events, it acquires data enriched in relevant content.

NATURE PORTFOLIO2022

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Patient-Derived Xenografts (PDXs) are the preclinical models which best recapitulate inter- and intra-patient complexity of human breast malignancies, and are also emerging as useful tools to study the normal breast epithelium. However, data analysis generated with such models is often confounded by the presence of host cells and can give rise to data misinterpretation. For instance, it is important to discriminate between xenografted and host cells in histological sections prior to performing immunostainings. We developed Single Cell Classifier (SCC), a data-driven deep learning-based computational tool that provides an innovative approach for automated cell species discrimination based on a multi-step process entailing nuclei segmentation and single cell classification. We show that human and murine cell contextual features, more than cell-intrinsic ones, can be exploited to discriminate between cell species in both normal and malignant tissues, yielding up to 96% classification accuracy. SCC will facilitate the interpretation of H&E- and DAPI-stained histological sections of xenografted human-in-mouse tissues and it is open to new in-house built models for further applications. SCC is released as an open-source plugin in ImageJ/Fiji available at the following link: https://github.com/Biomedical-Imaging-Group/SingleCellClassifier.

2021

EASI-FISH for thick tissue defines lateral hypothalamus spatio-molecular organization

Martin Weigert, Hui Yang

Determining the spatial organization and morphological characteristics of molecularly defined cell types is a major bottleneck for characterizing the architecture underpinning brain function. We developed Expansion Assisted Iterative Fluorescence In Situ Hybridization (EASI-FISH) to survey gene expression in brain tissue, as well as a turnkey computational pipeline to rapidly process large EASI-FISH image datasets. EASI-FISH was optimized for thick brain sections (300 mm) to facilitate reconstruction of spatio-molecular domains that generalize across brains. Using the EASI-FISH pipeline, we investigated the spatial distribution of dozens of molecularly defined cell types in the lateral hypothalamic area (LHA), a brain region with poorly defined anatomical organization. Mapping cell types in the LHA revealed nine spatially and molecularly defined subregions. EASI-FISH also facilitates iterative reanalysis of scRNA-seq datasets to determine marker-genes that further dissociated spatial and morphological heterogeneity. The EASI-FISH pipeline democratizes mapping molecularly defined cell types, enabling discoveries about brain organization.

CELL PRESS2021

Removing Structured Noise With Self-Supervised Blind-Spot Networks

Martin Weigert

Removal of noise from fluorescence microscopy images is an important first step in many biological analysis pipelines. Current state-of-the-art supervised methods employ convolutional neural networks that are trained with clean (ground-truth) images. Recently, it was shown that self-supervised image denoising with blind spot networks achieves excellent performance even when ground-truth images are not available, as is common in fluorescence microscopy. However, these approaches, e.g. Noise2Void ( N2V), generally assume pixel-wise independent noise, thus limiting their applicability in situations where spatially correlated (structured) noise is present. To overcome this limitation, we present Structured Noise2Void (STRUCTN2V), a generalization of blind spot networks that enables removal of structured noise without requiring an explicit noise model or ground truth data. Specifically, we propose to use an extended blind mask (rather than a single pixel/blind spot), whose shape is adapted to the structure of the noise. We evaluate our approach on two real datasets and show that STRUCTN2V considerably improves the removal of structured noise compared to existing standard and blind-spot based techniques.

IEEE2020