bioRxiv Science⌕ Search

bioRxiv · 10.1101/2022.08.29.505633

Small Training Dataset Convolutional Neural Networks for Application Specific Super-Resolution Microscopy

Abstract

SignificanceMachine learning (ML) models based on deep convolutional neural networks have been used to significantly increase microscopy resolution, speed (signal-to-noise ratio), and data interpretation. The bottleneck in developing effective ML systems is often the need to acquire large datasets to train the neural network. This paper demonstrates how adding a "dense encoder-decoder" block can be used to effectively train a neural network that produces super-resolution images from conventional microscopy diffraction-limited images trained using a small dataset (15 field-of-views). AimML helps to retrieve super-resolution information from a diffraction-limited image when trained with a massive training dataset. The aim of this work is to demonstrate a neural network that estimates super-resolution images from diffraction-limited images using modifications that enable training with a small dataset. ApproachWe employ "Dense Encoder-Decoder" (called DenseED) blocks in existing super-resolution ML network architectures. DenseED blocks use a dense layer that concatenates features from the previous convolutional layer to the next convolutional layer. DenseED blocks in fully convolutional networks (FCNs) estimate the super-resolution images when trained with a small training dataset (15 field-of-views) of human cells from the Widefield2SIM dataset and in fluorescent-labeled fixed bovine pulmonary artery endothelial cells (BPAE samples). ResultsConventional ML models without DenseED blocks trained on small datasets fail to accurately estimate super-resolution images while models including the DenseED blocks can. The average peak signal-to-noise ratio (PSNR) and resolution improvements achieved by networks containing DenseED blocks are {approx}3.2 dB and 2x, respectively. We evaluated various configurations of target image generation methods (e.g, experimentally captured target and computationally generated target) that are used to train FCNs with and without DenseED blocks and showed including DenseED blocks in simple FCNs outperforms compared to simple FCNs without DenseED blocks. ConclusionsDenseED blocks in neural networks show accurate extraction of super-resolution images even if the ML model is trained with a small training dataset of 15 field-of-views. This approach shows that microscopy applications can use DenseED blocks to train on smaller datasets that are application-specific imaging platforms and there is a promise for applying this to other imaging modalities such as MRI/X-ray, etc.

Source connections

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mannam, V., Howard, S.. 2022-08-29. Small Training Dataset Convolutional Neural Networks for Application Specific Super-Resolution Microscopy. https://doi.org/10.1101/2022.08.29.505633

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

The Unreasonable Effectiveness of Cell Types in Describing Neuronal Physiological Features

Single-cell RNA sequencing (scRNA-seq) captures detailed gene expression profiles at scale, while patch-clamp recordings measure intrinsic neuronal electrophysiological properties. Modeling the relations between these two modalities remains a challenge. Here, we compare how well electrophysiological features can be predicted by traditional transcriptomic cell type classification, representations derived from a foundational model (scGPT) pretrained on large-scale scRNA-seq datasets, ion channel-coding genes, and highly variable genes. Using paired transcriptomic and electrophysiological patch-sequencing data from 495 human neurons from neurosurgical tissue, we find that cluster-level cell type representations consistently outperform highly variable gene selection, ion channel gene selection, and context-enriched scGPT embeddings. Notably, performance varies across model architectures and initializations, and the best results are obtained by combining the outputs of separate cell type and scGPT-based models. Together, these findings suggest that traditional discrete cellular classification is highly effective in predicting physiological features. For maximum performance it can be complemented by pretrained transformer models.

neuroscience↗

A nonlinear inhibition pathway underlying cortical responses to tuned holographic optogenetic perturbations

Optogenetics enables causal manipulation of cortical activity. Perturbation responses can be counterintuitive due to network interactions, making theory essential for predicting them. Existing approaches often rely on linear approximations, which fail for many biologically relevant perturbations. Here we develop a nonlinear theory of responses to holographic perturbations in cell-type-specific recurrent networks with structured connectivity. We fit a nonlinear model to mouse V1 data, which shows cotuned-ensemble suppression: perturbing spatially clustered neurons with similar preferred orientations yields markedly stronger short-range suppression than perturbing untuned ensembles. We show that cotuned-ensemble suppression arises from a feature-tuned, nonlinear inhibition pathway implicating somatostatin-positive (SST) interneurons. The theory predicts that cotuned ensembles suppress parvalbumin-positive (PV) neurons but facilitate SST neurons, and links the degree of cotuned-ensemble suppression or facilitation to the variance of the SST response. This framework identifies mechanisms by which nonlinear inhibition sculpts cortical dynamics and establishes a predictive basis for targeted optogenetic interventions.

neuroscience↗

Proteomic signatures of APOE ε4 across human tissues and cell types in Alzheimers disease

The apolipoprotein E {varepsilon}4 (APOE {varepsilon}4) allele is the strongest genetic risk factor for late-onset Alzheimers disease (AD). However, the underlying molecular mechanisms remain unclear. This study included 1691 participants from the Religious Orders Study and Rush Memory and Aging Project (ROSMAP), 1226 participants from the Accelerating Medicines Partnership - Alzheimers Disease (AMP-AD) Diverse Cohorts Study, and 735 participants from the Alzheimers Disease Neuroimaging Initiative (ADNI). To characterise APOE {varepsilon}4 molecular effects, we analysed proteomic data from plasma, cerebrospinal fluid (CSF), and induced pluripotent stem cell (iPSC)-derived astrocytes and neurons, as well as transcriptomic and proteomic data from multiple brain regions. The association of APOE {varepsilon}4 with AD neuropathology was also examined. APOE {varepsilon}4 carriers shared a plasma proteomic signature enriched for immune processes, irrespective of AD diagnosis. A machine learning classifier trained on this signature discriminated APOE {varepsilon}4 carriers from non-carriers in an independent cohort using CSF proteomics. APOE {varepsilon}4 carriage was associated with higher Braak stages and Consortium to Establish a Registry for Alzheimers Disease (CERAD) score. However, only limited APOE {varepsilon}4-associated transcriptomic and proteomic changes were observed in bulk brain tissue, with poor cross-layer concordance. Proteomic analyses of iPSC-derived astrocytes and neurons further revealed cell-type-specific APOE {varepsilon}4-associated changes. APOE {varepsilon}4 is associated with a consistent proteomic signature across plasma and CSF. Its molecular effects in the brain differ across cell types, brain regions and molecular layers. These findings support the need for cell-type-resolved multi-omic studies to elucidate how APOE {varepsilon}4 confers AD risk.

neuroscience↗