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Biology subjects

Spengler, D.

Publications and source records attributed to Spengler, D..

3 recordsLinked to original sources

Reducing Manual Labour in Forensic Microtrace Recognition with Deep Learning

Forensic microtrace investigation relies on time- and labor-intensive microscopic analyses. To aid forensic experts in their investigations, an image recognition model for microtrace localisation and classification is needed. In this work, we use deep learning to automate trace recognition in images captured with automated microscopy. We localise and classify fibres, hairs, skin, glass and sand in microscopy scans through pixel-wise classification of tape-lift samples. As deep learning requires extensive amounts of annotated training data, we additionally investigate various pretraining strategies to minimise the required annotation workload. We compare ImageNet pretraining, pretraining with self-supervised learning and a sequential application of these approaches. We find that pretrained models are able to reduce the required annotated data twofold compared to models trained from scratch while retaining the prediction accuracy. While our ImageNet-pretrained models outperform our self-supervised-pretrained models, we achieve the highest accuracy by combining the two approaches, resulting in a factor of 4 reduction of manual annotated microtraces or a 65 % improvement in recognition and localisation accuracy (mean intersection over union increases from 0.34 to 0.56 due to pretraining) when training on only 2.2 dm2 of annotated tape lift scans. Our model is, therefore, the method of choice for the automatic analysis of large forensic microtrace scans.

bioinformatics↗

CLEAR-IT: Contrastive Learning Enabled Accurate Registration of Immune and Tumor cells from multiplexed images with limited labels in a platform-independent manner

Accurate phenotyping of cells in the tumor microenvironment is crucial for understanding cancer biology and developing effective therapies. However, current methods require precise cell segmentations and struggle to generalize across different imaging modalities, limiting their utility in digital pathology. Here, we show that Contrastive Learning Enabled Accurate Registration of Immune and Tumor Cells (CLEAR-IT) overcomes these limitations, providing a robust and versatile tool for cell phenotyping. CLEAR-IT accurately phenotypes cells comparable to state-of-the-art methods, generalizes across multiplex imaging modalities, maintains high performance even with limited number of labels, and enables the extraction of prognostic markers. Additionally, CLEAR-IT can be combined with existing methods to boost their performance, whereas its lack of need for precise cell segmentations significantly reduces training efforts. This method enhances the robustness and efficiency of digital pathology workflows, making it a valuable tool for cancer research and diagnostics.

bioinformatics↗

Polygenic risk for schizophrenia converges on alternative polyadenylation as molecular mechanism underlying synaptic impairment

Schizophrenia (SCZ) is a genetically heterogenous psychiatric disorder of highly polygenic nature. Correlative evidence from genetic studies indicate that the aggregated effects of distinct genetic risk factor combinations found in each patient converge onto common molecular mechanisms. To prove this on a functional level, we employed a reductionistic cellular model system for polygenic risk by differentiating induced pluripotent stem cells (iPSCs) from 104 individuals with high polygenic risk load and controls into cortical glutamatergic neurons (iNs). Multi-omics profiling identified widespread differences in alternative polyadenylation (APA) in the 3 untranslated region of many synaptic transcripts between iNs from SCZ patients and healthy donors. On the cellular level, 3APA was associated with a reduction in synaptic density of iNs. Importantly, differential APA was largely conserved between postmortem human prefrontal cortex from SCZ patients and healthy donors, and strongly enriched for transcripts related to synapse biology. 3APA was highly correlated with SCZ polygenic risk and affected genes were significantly enriched for SCZ associated common genetic variation. Integrative functional genomic analysis identified the RNA binding protein and SCZ GWAS risk gene PTBP2 as a critical trans-acting factor mediating 3APA of synaptic genes in SCZ subjects. Functional characterization of PTBP2 in iNs confirmed its key role in 3APA of synaptic transcripts and regulation of synapse density. Jointly, our findings show that the aggregated effects of polygenic risk converge on 3APA as one common molecular mechanism that underlies synaptic impairments in SCZ.

neuroscience↗