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Reliable prediction of pediatric obesity can offer a valuable resource to providers, helping them engage in timely preventive interventions before the disease is established. Many efforts have been made to develop ML-based predictive models of obesity, and some studies have reported high predictive performances. However, no commonly used clinical decision support tool based on existing ML models currently exists. This study presents a novel end-to-end pipeline specifically designed for pediatric obesity prediction, which supports the entire process of data extraction, inference, and communication via an API or a user interface. While focusing only on routinely recorded data in pediatric electronic health records (EHRs), our pipeline uses a diverse expert-curated list of medical concepts to predict the 1-3 years risk of developing obesity. Furthermore, by using the Fast Healthcare Interoperability Resources (FHIR) standard in our design procedure, we specifically target facilitating low-effort integration of our pipeline with different EHR systems. In our experiments, we report the effectiveness of the predictive model as well as its alignment with the feedback from various stakeholders, including ML scientists, providers, health IT personnel, health administration representatives, and patient group representatives.

Navigating unmanned aerial vehicles in environments where GPS signals are unavailable poses a compelling and intricate challenge. This challenge is further heightened when dealing with Nano Aerial Vehicles (NAVs) due to their compact size, payload restrictions, and computational capabilities. This paper proposes an approach for localization using off-board computing, an off-board monocular camera, and modified open-source algorithms. The proposed method uses three parallel proportional-integral-derivative controllers on the off-board computer to provide velocity corrections via wireless communication, stabilizing the NAV in a custom-controlled environment. Featuring a 3.1cm localization error and a modest setup cost of 50 USD, this approach proves optimal for environments where cost considerations are paramount. It is especially well-suited for applications like teaching drone control in academic institutions, where the specified error margin is deemed acceptable. Various applications are designed to validate the proposed technique, such as landing the NAV on a moving ground vehicle, path planning in a 3D space, and localizing multi-NAVs. The created package is openly available at https://github.com/simmubhangu/eyantra_drone to foster research in this field., Comment: 26 pages. Submitted to Cyber-Physical Systems journal

Large language models (LLMs) have shown impressive potential in helping with numerous medical challenges. Deploying LLMs in high-stakes applications such as medicine, however, brings in many concerns. One major area of concern relates to biased behaviors of LLMs in medical applications, leading to unfair treatment of individuals. To pave the way for the responsible and impactful deployment of Med LLMs, rigorous evaluation is a key prerequisite. Due to the huge complexity and variability of different medical scenarios, existing work in this domain has primarily relied on using manually crafted datasets for bias evaluation. In this study, we present a new method to scale up such bias evaluations by automatically generating test cases based on rigorous medical evidence. We specifically target the challenges of a) domain-specificity of bias characterization, b) hallucinating while generating the test cases, and c) various dependencies between the health outcomes and sensitive attributes. To that end, we offer new methods to address these challenges integrated with our generative pipeline, using medical knowledge graphs, medical ontologies, and customized general LLM evaluation frameworks in our method. Through a series of extensive experiments, we show that the test cases generated by our proposed method can effectively reveal bias patterns in Med LLMs at larger and more flexible scales than human-crafted datasets. We publish a large bias evaluation dataset using our pipeline, which is dedicated to a few medical case studies. A live demo of our application for vignette generation is available at https://vignette.streamlit.app. Our code is also available at https://github.com/healthylaife/autofair.

Existing multimodal retrieval benchmarks primarily focus on evaluating whether models can retrieve and utilize external textual knowledge for question answering. However, there are scenarios where retrieving visual information is either more beneficial or easier to access than textual data. In this paper, we introduce a multimodal retrieval-augmented generation benchmark, MRAG-Bench, in which we systematically identify and categorize scenarios where visually augmented knowledge is better than textual knowledge, for instance, more images from varying viewpoints. MRAG-Bench consists of 16,130 images and 1,353 human-annotated multiple-choice questions across 9 distinct scenarios. With MRAG-Bench, we conduct an evaluation of 10 open-source and 4 proprietary large vision-language models (LVLMs). Our results show that all LVLMs exhibit greater improvements when augmented with images compared to textual knowledge, confirming that MRAG-Bench is vision-centric. Additionally, we conduct extensive analysis with MRAG-Bench, which offers valuable insights into retrieval-augmented LVLMs. Notably, the top-performing model, GPT-4o, faces challenges in effectively leveraging retrieved knowledge, achieving only a 5.82% improvement with ground-truth information, in contrast to a 33.16% improvement observed in human participants. These findings highlight the importance of MRAG-Bench in encouraging the community to enhance LVLMs' ability to utilize retrieved visual knowledge more effectively., Comment: https://mragbench.github.io

Federated Learning is a well-researched approach for collaboratively training machine learning models across decentralized data while preserving privacy. However, integrating Homomorphic Encryption to ensure data confidentiality introduces significant computational and communication overheads, particularly in heterogeneous environments where clients have varying computational capacities and security needs. In this paper, we propose HERL, a Reinforcement Learning-based approach that uses Q-Learning to dynamically optimize encryption parameters, specifically the polynomial modulus degree, $N$, and the coefficient modulus, $q$, across different client tiers. Our proposed method involves first profiling and tiering clients according to the chosen clustering approach, followed by dynamically selecting the most suitable encryption parameters using an RL-agent. Experimental results demonstrate that our approach significantly reduces the computational overhead while maintaining utility and a high level of security. Empirical results show that HERL improves utility by 17%, reduces the convergence time by up to 24%, and increases convergence efficiency by up to 30%, with minimal security loss.

Large Language Models (LLMs) have emerged as promising solutions for a variety of medical and clinical decision support applications. However, LLMs are often subject to different types of biases, which can lead to unfair treatment of individuals, worsening health disparities, and reducing trust in AI-augmented medical tools. Aiming to address this important issue, in this study, we present a new model alignment approach for aligning LLMs using a preference optimization method within a knowledge distillation framework. Prior to presenting our proposed method, we first use an evaluation framework to conduct a comprehensive (largest to our knowledge) empirical evaluation to reveal the type and nature of existing biases in LLMs used for medical applications. We then offer a bias mitigation technique to reduce the unfair patterns in LLM outputs across different subgroups identified by the protected attributes. We show that our mitigation method is effective in significantly reducing observed biased patterns. Our code is publicly available at \url{https://github.com/healthylaife/FairAlignmentLLM}., Comment: arXiv admin note: substantial text overlap with arXiv:2404.15149

Machine learning in computational pathology (CPath) often aggregates patch-level predictions from multi-gigapixel Whole Slide Images (WSIs) to generate WSI-level prediction scores for crucial tasks such as survival prediction and drug effect prediction. However, current methods do not explicitly characterize distributional differences between patch sets within WSIs. We introduce HistoKernel, a novel Maximum Mean Discrepancy (MMD) kernel that measures distributional similarity between WSIs for enhanced prediction performance on downstream prediction tasks. Our comprehensive analysis demonstrates HistoKernel's effectiveness across various machine learning tasks, including retrieval (n = 9,362), drug sensitivity regression (n = 551), point mutation classification (n = 3,419), and survival analysis (n = 2,291), outperforming existing deep learning methods. Additionally, HistoKernel seamlessly integrates multi-modal data and offers a novel perturbation-based method for patch-level explainability. This work pioneers the use of kernel-based methods for WSI-level predictive modeling, opening new avenues for research. Code is available at https://github.com/pkeller00/HistoKernel., Comment: 28 pages, 5 figures, 1 Table. Preprint for article in review at Nature Machine Intelligence

We study how well large language models (LLMs) explain their generations through rationales -- a set of tokens extracted from the input text that reflect the decision-making process of LLMs. Specifically, we systematically study rationales derived using two approaches: (1) popular prompting-based methods, where prompts are used to guide LLMs in generating rationales, and (2) technical attribution-based methods, which leverage attention or gradients to identify important tokens. Our analysis spans three classification datasets with annotated rationales, encompassing tasks with varying performance levels. While prompting-based self-explanations are widely used, our study reveals that these explanations are not always as "aligned" with the human rationale as attribution-based explanations. Even more so, fine-tuning LLMs to enhance classification task accuracy does not enhance the alignment of prompting-based rationales. Still, it does considerably improve the alignment of attribution-based methods (e.g., InputXGradient). More importantly, we show that prompting-based self-explanation is also less "faithful" than attribution-based explanations, failing to provide a reliable account of the model's decision-making process. To evaluate faithfulness, unlike prior studies that excluded misclassified examples, we evaluate all instances and also examine the impact of fine-tuning and accuracy on alignment and faithfulness. Our findings suggest that inconclusive faithfulness results reported in earlier studies may stem from low classification accuracy. These findings underscore the importance of more rigorous and comprehensive evaluations of LLM rationales.

Understanding human behavior fundamentally relies on accurate 3D human pose estimation. Graph Convolutional Networks (GCNs) have recently shown promising advancements, delivering state-of-the-art performance with rather lightweight architectures. In the context of graph-structured data, leveraging the eigenvectors of the graph Laplacian matrix for positional encoding is effective. Yet, the approach does not specify how to handle scenarios where edges in the input graph are missing. To this end, we propose a novel positional encoding technique, PerturbPE, that extracts consistent and regular components from the eigenbasis. Our method involves applying multiple perturbations and taking their average to extract the consistent and regular component from the eigenbasis. PerturbPE leverages the Rayleigh-Schrodinger Perturbation Theorem (RSPT) for calculating the perturbed eigenvectors. Employing this labeling technique enhances the robustness and generalizability of the model. Our results support our theoretical findings, e.g. our experimental analysis observed a performance enhancement of up to $12\%$ on the Human3.6M dataset in instances where occlusion resulted in the absence of one edge. Furthermore, our novel approach significantly enhances performance in scenarios where two edges are missing, setting a new benchmark for state-of-the-art.

Pathology reports are rich in clinical and pathological details but are often presented in free-text format. The unstructured nature of these reports presents a significant challenge limiting the accessibility of their content. In this work, we present a practical approach based on the use of large multimodal models (LMMs) for automatically extracting information from scanned images of pathology reports with the goal of generating a standardised report specifying the value of different fields along with estimated confidence about the accuracy of the extracted fields. The proposed approach overcomes limitations of existing methods which do not assign confidence scores to extracted fields limiting their practical use. The proposed framework uses two stages of prompting a Large Multimodal Model (LMM) for information extraction and validation. The framework generalises to textual reports from multiple medical centres as well as scanned images of legacy pathology reports. We show that the estimated confidence is an effective indicator of the accuracy of the extracted information that can be used to select only accurately extracted fields. We also show the prognostic significance of structured and unstructured data from pathology reports and show that the automatically extracted field values significant prognostic value for patient stratification. The framework is available for evaluation via the URL: https://labieb.dcs.warwick.ac.uk/., Comment: 19 pages, 6 figures

Large Language Models (LLMs) have emerged as powerful candidates to inform clinical decision-making processes. While these models play an increasingly prominent role in shaping the digital landscape, two growing concerns emerge in healthcare applications: 1) to what extent do LLMs exhibit social bias based on patients' protected attributes (like race), and 2) how do design choices (like architecture design and prompting strategies) influence the observed biases? To answer these questions rigorously, we evaluated eight popular LLMs across three question-answering (QA) datasets using clinical vignettes (patient descriptions) standardized for bias evaluations. We employ red-teaming strategies to analyze how demographics affect LLM outputs, comparing both general-purpose and clinically-trained models. Our extensive experiments reveal various disparities (some significant) across protected groups. We also observe several counter-intuitive patterns such as larger models not being necessarily less biased and fined-tuned models on medical data not being necessarily better than the general-purpose models. Furthermore, our study demonstrates the impact of prompt design on bias patterns and shows that specific phrasing can influence bias patterns and reflection-type approaches (like Chain of Thought) can reduce biased outcomes effectively. Consistent with prior studies, we call on additional evaluations, scrutiny, and enhancement of LLMs used in clinical decision support applications.

Creating plasmonic nanoparticles on a tapered optical fiber tip enables a remote SERS sensing probe, ideal for challenging sampling scenarios like biological tissue, specific cells, on-site environmental monitoring, and deep brain structures. However, nanoparticle patterns fabricated from current bottom-up methods are mostly random, making geometry control difficult. Uneven statistical distribution, clustering, and multilayer deposition introduce uncertainty in correlating device performance with morphology. Here, we employ a tunable solid-state dewetting method to create densely packed monolayer Au nanoislands (NIs) with varied geometric parameters, directly contacting the silica TF surface. These patterns exhibit analyzable nanoparticle sizes, densities, and uniform distribution across the entire taper surface, enabling a systematic investigation of particle size, density, and analyte effects on the SERS performance of the through-fiber detection system. The study is focused on the SERS response of a widely employed benchmark Rhodamine 6G molecule and Serotonin, a neurotransmitter with high relevance for the neuroscience field. The numerical simulations and limit of detection (LOD) experiments on R6G show that the increase of the total near-field enhancement volume promotes the SERS sensitivity of the probe. However, for serotonin we observed a different behavior linked to its interaction with the nanoparticle's surface. The obtained LOD is as low as 10-7 M, a value not achieved so far in a through-fiber detection scheme. Therefore, we believe our work offers a strategy to design nanoparticle-based remote SERS sensing probes and provide new clues to discover and understand the intricate plasmonic-driven chemical reactions.

While current large language models (LLMs) perform well on many knowledge-related tasks, they are limited by relying on their parameters as an implicit storage mechanism. As a result, they struggle with memorizing rare events and with updating their memory as facts change over time. In addition, the uninterpretable nature of parametric memory makes it challenging to prevent hallucination. Model editing and augmenting LLMs with parameters specialized for memory are only partial solutions. In this paper, we introduce MemLLM, a novel method of enhancing LLMs by integrating a structured and explicit read-and-write memory module. MemLLM tackles the aforementioned challenges by enabling dynamic interaction with the memory and improving the LLM's capabilities in using stored knowledge. Our experiments indicate that MemLLM enhances the LLM's performance and interpretability, in language modeling in general and knowledge-intensive tasks in particular. We see MemLLM as an important step towards making LLMs more grounded and factual through memory augmentation.

Polysomnography (PSG) is a type of sleep study that records multimodal physiological signals and is widely used for purposes such as sleep staging and respiratory event detection. Conventional machine learning methods assume that each sleep study is associated with a fixed set of observed modalities and that all modalities are available for each sample. However, noisy and missing modalities are a common issue in real-world clinical settings. In this study, we propose a comprehensive pipeline aiming to compensate for the missing or noisy modalities when performing sleep apnea detection. Unlike other existing studies, our proposed model works with any combination of available modalities. Our experiments show that the proposed model outperforms other state-of-the-art approaches in sleep apnea detection using various subsets of available data and different levels of noise, and maintains its high performance (AUROC>0.9) even in the presence of high levels of noise or missingness. This is especially relevant in settings where the level of noise and missingness is high (such as pediatric or outside-of-clinic scenarios).

Digital pathology has gained significant traction in modern healthcare systems. This shift from optical microscopes to digital imagery brings with it the potential for improved diagnosis, efficiency, and the integration of AI tools into the pathologists workflow. A critical aspect of this is visualization. Throughout the development of a machine learning (ML) model in digital pathology, it is crucial to have flexible, openly available tools to visualize models, from their outputs and predictions to the underlying annotations and images used to train or test a model. We introduce TIAViz, a Python-based visualization tool built into TIAToolbox which allows flexible, interactive, fully zoomable overlay of a wide variety of information onto whole slide images, including graphs, heatmaps, segmentations, annotations and other WSIs. The UI is browser-based, allowing use either locally, on a remote machine, or on a server to provide publicly available demos. This tool is open source and is made available at: https://github.com/TissueImageAnalytics/tiatoolbox and via pip installation (pip install tiatoolbox) and conda as part of TIAToolbox., Comment: Application note to be submitted to bioinformatics

Quantum machine learning with quantum kernels for classification problems is a growing area of research. Recently, quantum kernel alignment techniques that parameterise the kernel have been developed, allowing the kernel to be trained and therefore aligned with a specific dataset. While quantum kernel alignment is a promising technique, it has been hampered by considerable training costs because the full kernel matrix must be constructed at every training iteration. Addressing this challenge, we introduce a novel method that seeks to balance efficiency and performance. We present a sub-sampling training approach that uses a subset of the kernel matrix at each training step, thereby reducing the overall computational cost of the training. In this work, we apply the sub-sampling method to synthetic datasets and a real-world breast cancer dataset and demonstrate considerable reductions in the number of circuits required to train the quantum kernel while maintaining classification accuracy., Comment: Paper as accepted on Quantum on 2024-09-18. The method showcased in this work is also available as a Jupyter notebook at https://github.com/qiskit-community/qiskit-machine-learning/tree/IEEE2024

Deep learning models have exhibited exceptional effectiveness in Computational Pathology (CPath) by tackling intricate tasks across an array of histology image analysis applications. Nevertheless, the presence of out-of-distribution data (stemming from a multitude of sources such as disparate imaging devices and diverse tissue preparation methods) can cause \emph{domain shift} (DS). DS decreases the generalization of trained models to unseen datasets with slightly different data distributions, prompting the need for innovative \emph{domain generalization} (DG) solutions. Recognizing the potential of DG methods to significantly influence diagnostic and prognostic models in cancer studies and clinical practice, we present this survey along with guidelines on achieving DG in CPath. We rigorously define various DS types, systematically review and categorize existing DG approaches and resources in CPath, and provide insights into their advantages, limitations, and applicability. We also conduct thorough benchmarking experiments with 28 cutting-edge DG algorithms to address a complex DG problem. Our findings suggest that careful experiment design and CPath-specific Stain Augmentation technique can be very effective. However, there is no one-size-fits-all solution for DG in CPath. Therefore, we establish clear guidelines for detecting and managing DS depending on different scenarios. While most of the concepts, guidelines, and recommendations are given for applications in CPath, we believe that they are applicable to most medical image analysis tasks as well., Comment: Extended Version

Oral epithelial dysplasia (OED) is a premalignant histopathological diagnosis given to lesions of the oral cavity. Its grading suffers from significant inter-/intra- observer variability, and does not reliably predict malignancy progression, potentially leading to suboptimal treatment decisions. To address this, we developed a novel artificial intelligence algorithm that can assign an Oral Malignant Transformation (OMT) risk score, based on histological patterns in the in Haematoxylin and Eosin stained whole slide images, to quantify the risk of OED progression. The algorithm is based on the detection and segmentation of nuclei within (and around) the epithelium using an in-house segmentation model. We then employed a shallow neural network fed with interpretable morphological/spatial features, emulating histological markers. We conducted internal cross-validation on our development cohort (Sheffield; n = 193 cases) followed by independent validation on two external cohorts (Birmingham and Belfast; n = 92 cases). The proposed OMTscore yields an AUROC = 0.74 in predicting whether an OED progresses to malignancy or not. Survival analyses showed the prognostic value of our OMTscore for predicting malignancy transformation, when compared to the manually-assigned WHO and binary grades. Analysis of the correctly predicted cases elucidated the presence of peri-epithelial and epithelium-infiltrating lymphocytes in the most predictive patches of cases that transformed (p < 0.0001). This is the first study to propose a completely automated algorithm for predicting OED transformation based on interpretable nuclear features, whilst being validated on external datasets. The algorithm shows better-than-human-level performance for prediction of OED malignant transformation and offers a promising solution to the challenges of grading OED in routine clinical practice.

We theoretically propose a strategy to address an individual spin in a large array of spin qubits with a random distribution of g-factors by employing a combination of single-qubit and SWAP gates facilitated by a global microwave field and local exchange pulses. Consequently, only the target qubit undergoes the desired operation and all other qubits return to their original states, even qubits that share the same Larmor frequency as the target. Gate fidelities above 99% can thus be maintained for arrays containing tens of qubits.

An emerging solution for explaining Transformer-based models is to use vector-based analysis on how the representations are formed. However, providing a faithful vector-based explanation for a multi-layer model could be challenging in three aspects: (1) Incorporating all components into the analysis, (2) Aggregating the layer dynamics to determine the information flow and mixture throughout the entire model, and (3) Identifying the connection between the vector-based analysis and the model's predictions. In this paper, we present DecompX to tackle these challenges. DecompX is based on the construction of decomposed token representations and their successive propagation throughout the model without mixing them in between layers. Additionally, our proposal provides multiple advantages over existing solutions for its inclusion of all encoder components (especially nonlinear feed-forward networks) and the classification head. The former allows acquiring precise vectors while the latter transforms the decomposition into meaningful prediction-based values, eliminating the need for norm- or summation-based vector aggregation. According to the standard faithfulness evaluations, DecompX consistently outperforms existing gradient-based and vector-based approaches on various datasets. Our code is available at https://github.com/mohsenfayyaz/DecompX., Comment: Accepted to ACL 2023 (main conference)

Large language models (LLMs) have significantly advanced the field of natural language processing (NLP) through their extensive parameters and comprehensive data utilization. However, existing LLMs lack a dedicated memory unit, limiting their ability to explicitly store and retrieve knowledge for various tasks. In this paper, we propose RET-LLM a novel framework that equips LLMs with a general write-read memory unit, allowing them to extract, store, and recall knowledge from the text as needed for task performance. Inspired by Davidsonian semantics theory, we extract and save knowledge in the form of triplets. The memory unit is designed to be scalable, aggregatable, updatable, and interpretable. Through qualitative evaluations, we demonstrate the superiority of our proposed framework over baseline approaches in question answering tasks. Moreover, our framework exhibits robust performance in handling temporal-based question answering tasks, showcasing its ability to effectively manage time-dependent information., Comment: NOTE: This concept paper outlines an initial methodology, now evolved and thoroughly evaluated in the MemLLM paper

Generating realistic tissue images with annotations is a challenging task that is important in many computational histopathology applications. Synthetically generated images and annotations are valuable for training and evaluating algorithms in this domain. To address this, we propose an interactive framework generating pairs of realistic colorectal cancer histology images with corresponding glandular masks from glandular structure layouts. The framework accurately captures vital features like stroma, goblet cells, and glandular lumen. Users can control gland appearance by adjusting parameters such as the number of glands, their locations, and sizes. The generated images exhibit good Frechet Inception Distance (FID) scores compared to the state-of-the-art image-to-image translation model. Additionally, we demonstrate the utility of our synthetic annotations for evaluating gland segmentation algorithms. Furthermore, we present a methodology for constructing glandular masks using advanced deep generative models, such as latent diffusion models. These masks enable tissue image generation through a residual encoder-decoder network.

The non-uniform photoelectric response of infrared imaging systems results in fixed-pattern stripe noise being superimposed on infrared images, which severely reduces image quality. As the applications of degraded infrared images are limited, it is crucial to effectively preserve original details. Existing image destriping methods struggle to concurrently remove all stripe noise artifacts, preserve image details and structures, and balance real-time performance. In this paper we propose a novel algorithm for destriping degraded images, which takes advantage of neighbouring column signal correlation to remove independent column stripe noise. This is achieved through an iterative deep unfolding algorithm where the estimated noise of one network iteration is used as input to the next iteration. This progression substantially reduces the search space of possible function approximations, allowing for efficient training on larger datasets. The proposed method allows for a more precise estimation of stripe noise to preserve scene details more accurately. Extensive experimental results demonstrate that the proposed model outperforms existing destriping methods on artificially corrupted images on both quantitative and qualitative assessments., Comment: Accepted in the International Joint Conference on Neural Networks (IJCNN) track of the 2022 IEEE World Congress on Computational Intelligence (IEEE WCCI 2022)

Nuclear detection, segmentation and morphometric profiling are essential in helping us further understand the relationship between histology and patient outcome. To drive innovation in this area, we setup a community-wide challenge using the largest available dataset of its kind to assess nuclear segmentation and cellular composition. Our challenge, named CoNIC, stimulated the development of reproducible algorithms for cellular recognition with real-time result inspection on public leaderboards. We conducted an extensive post-challenge analysis based on the top-performing models using 1,658 whole-slide images of colon tissue. With around 700 million detected nuclei per model, associated features were used for dysplasia grading and survival analysis, where we demonstrated that the challenge's improvement over the previous state-of-the-art led to significant boosts in downstream performance. Our findings also suggest that eosinophils and neutrophils play an important role in the tumour microevironment. We release challenge models and WSI-level results to foster the development of further methods for biomarker discovery.

Malignant mesothelioma is classified into three histological subtypes, Epithelioid, Sarcomatoid, and Biphasic according to the relative proportions of epithelioid and sarcomatoid tumor cells present. Biphasic tumors display significant populations of both cell types. This subtyping is subjective and limited by current diagnostic guidelines and can differ even between expert thoracic pathologists when characterising the continuum of relative proportions of epithelioid and sarcomatoid components using a three class system. In this work, we develop a novel dual-task Graph Neural Network (GNN) architecture with ranking loss to learn a model capable of scoring regions of tissue down to cellular resolution. This allows quantitative profiling of a tumor sample according to the aggregate sarcomatoid association score of all the cells in the sample. The proposed approach uses only core-level labels and frames the prediction task as a dual multiple instance learning (MIL) problem. Tissue is represented by a cell graph with both cell-level morphological and regional features. We use an external multi-centric test set from Mesobank, on which we demonstrate the predictive performance of our model. We validate our model predictions through an analysis of the typical morphological features of cells according to their predicted score, finding that some of the morphological differences identified by our model match known differences used by pathologists. We further show that the model score is predictive of patient survival with a hazard ratio of 2.30. The code for the proposed approach, along with the dataset, is available at: https://github.com/measty/MesoGraph.

How similar are two images? In computational pathology, where Whole Slide Images (WSIs) of digitally scanned tissue samples from patients can be multi-gigapixels in size, determination of degree of similarity between two WSIs is a challenging task with a number of practical applications. In this work, we explore a novel strategy based on kernelized Maximum Mean Discrepancy (MMD) analysis for determination of pairwise similarity between WSIs. The proposed approach works by calculating MMD between two WSIs using kernels over deep features of image patches. This allows representation of an entire dataset of WSIs as a kernel matrix for WSI level clustering, weakly-supervised prediction of TP-53 mutation status in breast cancer patients from their routine WSIs as well as survival analysis with state of the art prediction performance. We believe that this work will open up further avenues for application of WSI-level kernels for predictive and prognostic tasks in computational pathology., Comment: * Joint first authorship Accepted: IEEE - ISBI 2023 International Symposium on Biomedical Imaging

Since the introduction of digital and computational pathology as a field, one of the major problems in the clinical application of algorithms has been the struggle to generalize well to examples outside the distribution of the training data. Existing work to address this in both pathology and natural images has focused almost exclusively on classification tasks. We explore and evaluate the robustness of the 7 best performing nuclear segmentation and classification models from the largest computational pathology challenge for this problem to date, the CoNIC challenge. We demonstrate that existing state-of-the-art (SoTA) models are robust towards compression artifacts but suffer substantial performance reduction when subjected to shifts in the color domain. We find that using stain normalization to address the domain shift problem can be detrimental to the model performance. On the other hand, neural style transfer is more consistent in improving test performance when presented with large color variations in the wild., Comment: Oral presentation at MICCAI MLMI 2022, 7 pages, 6 figures

Automated synthesis of histology images has several potential applications in computational pathology. However, no existing method can generate realistic tissue images with a bespoke cellular layout or user-defined histology parameters. In this work, we propose a novel framework called SynCLay (Synthesis from Cellular Layouts) that can construct realistic and high-quality histology images from user-defined cellular layouts along with annotated cellular boundaries. Tissue image generation based on bespoke cellular layouts through the proposed framework allows users to generate different histological patterns from arbitrary topological arrangement of different types of cells. SynCLay generated synthetic images can be helpful in studying the role of different types of cells present in the tumor microenvironmet. Additionally, they can assist in balancing the distribution of cellular counts in tissue images for designing accurate cellular composition predictors by minimizing the effects of data imbalance. We train SynCLay in an adversarial manner and integrate a nuclear segmentation and classification model in its training to refine nuclear structures and generate nuclear masks in conjunction with synthetic images. During inference, we combine the model with another parametric model for generating colon images and associated cellular counts as annotations given the grade of differentiation and cell densities of different cells. We assess the generated images quantitatively and report on feedback from trained pathologists who assigned realism scores to a set of images generated by the framework. The average realism score across all pathologists for synthetic images was as high as that for the real images. We also show that augmenting limited real data with the synthetic data generated by our framework can significantly boost prediction performance of the cellular composition prediction task.

Denoising diffusion models, a class of generative models, have garnered immense interest lately in various deep-learning problems. A diffusion probabilistic model defines a forward diffusion stage where the input data is gradually perturbed over several steps by adding Gaussian noise and then learns to reverse the diffusion process to retrieve the desired noise-free data from noisy data samples. Diffusion models are widely appreciated for their strong mode coverage and quality of the generated samples despite their known computational burdens. Capitalizing on the advances in computer vision, the field of medical imaging has also observed a growing interest in diffusion models. To help the researcher navigate this profusion, this survey intends to provide a comprehensive overview of diffusion models in the discipline of medical image analysis. Specifically, we introduce the solid theoretical foundation and fundamental concepts behind diffusion models and the three generic diffusion modelling frameworks: diffusion probabilistic models, noise-conditioned score networks, and stochastic differential equations. Then, we provide a systematic taxonomy of diffusion models in the medical domain and propose a multi-perspective categorization based on their application, imaging modality, organ of interest, and algorithms. To this end, we cover extensive applications of diffusion models in the medical domain. Furthermore, we emphasize the practical use case of some selected approaches, and then we discuss the limitations of the diffusion models in the medical domain and propose several directions to fulfill the demands of this field. Finally, we gather the overviewed studies with their available open-source implementations at https://github.com/amirhossein-kz/Awesome-Diffusion-Models-in-Medical-Imaging., Comment: Third revision: including more papers and further discussions

Current pre-trained language models rely on large datasets for achieving state-of-the-art performance. However, past research has shown that not all examples in a dataset are equally important during training. In fact, it is sometimes possible to prune a considerable fraction of the training set while maintaining the test performance. Established on standard vision benchmarks, two gradient-based scoring metrics for finding important examples are GraNd and its estimated version, EL2N. In this work, we employ these two metrics for the first time in NLP. We demonstrate that these metrics need to be computed after at least one epoch of fine-tuning and they are not reliable in early steps. Furthermore, we show that by pruning a small portion of the examples with the highest GraNd/EL2N scores, we can not only preserve the test accuracy, but also surpass it. This paper details adjustments and implementation choices which enable GraNd and EL2N to be applied to NLP., Comment: ENLSP @ NeurIPS2022

Counting of mitotic figures is a fundamental step in grading and prognostication of several cancers. However, manual mitosis counting is tedious and time-consuming. In addition, variation in the appearance of mitotic figures causes a high degree of discordance among pathologists. With advances in deep learning models, several automatic mitosis detection algorithms have been proposed but they are sensitive to {\em domain shift} often seen in histology images. We propose a robust and efficient two-stage mitosis detection framework, which comprises mitosis candidate segmentation ({\em Detecting Fast}) and candidate refinement ({\em Detecting Slow}) stages. The proposed candidate segmentation model, termed \textit{EUNet}, is fast and accurate due to its architectural design. EUNet can precisely segment candidates at a lower resolution to considerably speed up candidate detection. Candidates are then refined using a deeper classifier network, EfficientNet-B7, in the second stage. We make sure both stages are robust against domain shift by incorporating domain generalization methods. We demonstrate state-of-the-art performance and generalizability of the proposed model on the three largest publicly available mitosis datasets, winning the two mitosis domain generalization challenge contests (MIDOG21 and MIDOG22). Finally, we showcase the utility of the proposed algorithm by processing the TCGA breast cancer cohort (1,125 whole-slide images) to generate and release a repository of more than 620K mitotic figures., Comment: Extended version of the work done for MIDOG challenge submission

There has been a growing interest in interpreting the underlying dynamics of Transformers. While self-attention patterns were initially deemed as the primary option, recent studies have shown that integrating other components can yield more accurate explanations. This paper introduces a novel token attribution analysis method that incorporates all the components in the encoder block and aggregates this throughout layers. Through extensive quantitative and qualitative experiments, we demonstrate that our method can produce faithful and meaningful global token attributions. Our experiments reveal that incorporating almost every encoder component results in increasingly more accurate analysis in both local (single layer) and global (the whole model) settings. Our global attribution analysis significantly outperforms previous methods on various tasks regarding correlation with gradient-based saliency scores. Our code is freely available at https://github.com/mohsenfayyaz/GlobEnc., Comment: Accepted to NAACL 2022 (main conference)

Human languages are full of metaphorical expressions. Metaphors help people understand the world by connecting new concepts and domains to more familiar ones. Large pre-trained language models (PLMs) are therefore assumed to encode metaphorical knowledge useful for NLP systems. In this paper, we investigate this hypothesis for PLMs, by probing metaphoricity information in their encodings, and by measuring the cross-lingual and cross-dataset generalization of this information. We present studies in multiple metaphor detection datasets and in four languages (i.e., English, Spanish, Russian, and Farsi). Our extensive experiments suggest that contextual representations in PLMs do encode metaphorical knowledge, and mostly in their middle layers. The knowledge is transferable between languages and datasets, especially when the annotation is consistent across training and testing sets. Our findings give helpful insights for both cognitive and NLP scientists., Comment: Accepted to ACL 2022 (main conference)

The recent surge in performance for image analysis of digitised pathology slides can largely be attributed to the advances in deep learning. Deep models can be used to initially localise various structures in the tissue and hence facilitate the extraction of interpretable features for biomarker discovery. However, these models are typically trained for a single task and therefore scale poorly as we wish to adapt the model for an increasing number of different tasks. Also, supervised deep learning models are very data hungry and therefore rely on large amounts of training data to perform well. In this paper, we present a multi-task learning approach for segmentation and classification of nuclei, glands, lumina and different tissue regions that leverages data from multiple independent data sources. While ensuring that our tasks are aligned by the same tissue type and resolution, we enable meaningful simultaneous prediction with a single network. As a result of feature sharing, we also show that the learned representation can be used to improve the performance of additional tasks via transfer learning, including nuclear classification and signet ring cell detection. As part of this work, we train our developed Cerberus model on a huge amount of data, consisting of over 600K objects for segmentation and 440K patches for classification. We use our approach to process 599 colorectal whole-slide images from TCGA, where we localise 377 million, 900K and 2.1 million nuclei, glands and lumina, respectively and make the results available to the community for downstream analysis.

Childhood obesity is a major public health concern. Multidisciplinary pediatric weight management programs are considered standard treatment for children with obesity and severe obesity who are not able to be successfully managed in the primary care setting; however, high drop-out rates (referred to as attrition) are a major hurdle in delivering successful interventions. Predicting attrition patterns can help providers reduce the attrition rates. Previous work has mainly focused on finding static predictors of attrition using statistical analysis methods. In this study, we present a machine learning model to predict (a) the likelihood of attrition, and (b) the change in body-mass index (BMI) percentile of children, at different time points after joining a weight management program. We use a five-year dataset containing the information related to around 4,550 children that we have compiled using data from the Nemours Pediatric Weight Management program. Our models show strong prediction performance as determined by high AUROC scores across different tasks (average AUROC of 0.75 for predicting attrition, and 0.73 for predicting weight outcomes). Additionally, we report the top features predicting attrition and weight outcomes in a series of explanatory experiments.

Motivation: Machine learning based prediction of compound-protein interactions (CPIs) is important for drug design, screening and repurposing studies and can improve the efficiency and cost-effectiveness of wet lab assays. Despite the publication of many research papers reporting CPI predictors in the recent years, we have observed a number of fundamental issues in experiment design that lead to over optimistic estimates of model performance. Results: In this paper, we analyze the impact of several important factors affecting generalization perfor-mance of CPI predictors that are overlooked in existing work: 1. Similarity between training and test examples in cross-validation 2. The strategy for generating negative examples, in the absence of experimentally verified negative examples. 3. Choice of evaluation protocols and performance metrics and their alignment with real-world use of CPI predictors in screening large compound libraries. Using both an existing state-of-the-art method (CPI-NN) and a proposed kernel based approach, we have found that assessment of predictive performance of CPI predictors requires careful con-trol over similarity between training and test examples. We also show that random pairing for gen-erating synthetic negative examples for training and performance evaluation results in models with better generalization performance in comparison to more sophisticated strategies used in existing studies. Furthermore, we have found that our kernel based approach, despite its simple design, exceeds the prediction performance of CPI-NN. We have used the proposed model for compound screening of several proteins including SARS-CoV-2 Spike and Human ACE2 proteins and found strong evidence in support of its top hits. Availability: Code and raw experimental results available at https://github.com/adibayaseen/HKRCPI Contact: Fayyaz.minhas@warwick.ac.uk, Comment: Supplementary information: Supplementary data files are available as part of the GitHub repository

Motivation: Digitization of pathology laboratories through digital slide scanners and advances in deep learning approaches for objective histological assessment have resulted in rapid progress in the field of computational pathology (CPath) with wide-ranging applications in medical and pharmaceutical research as well as clinical workflows. However, the estimation of robustness of CPath models to variations in input images is an open problem with a significant impact on the down-stream practical applicability, deployment and acceptability of these approaches. Furthermore, development of domain-specific strategies for enhancement of robustness of such models is of prime importance as well. Implementation and Availability: In this work, we propose the first domain-specific Robustness Evaluation and Enhancement Toolbox (REET) for computational pathology applications. It provides a suite of algorithmic strategies for enabling robustness assessment of predictive models with respect to specialized image transformations such as staining, compression, focusing, blurring, changes in spatial resolution, brightness variations, geometric changes as well as pixel-level adversarial perturbations. Furthermore, REET also enables efficient and robust training of deep learning pipelines in computational pathology. REET is implemented in Python and is available at the following URL: https://github.com/alexjfoote/reetoolbox. Contact: Fayyaz.minhas@warwick.ac.uk

Computational Pathology (CPath) is an emerging field concerned with the study of tissue pathology via computational algorithms for the processing and analysis of digitized high-resolution images of tissue slides. Recent deep learning based developments in CPath have successfully leveraged sheer volume of raw pixel data in histology images for predicting target parameters in the domains of diagnostics, prognostics, treatment sensitivity and patient stratification -- heralding the promise of a new data-driven AI era for both histopathology and oncology. With data serving as the fuel and AI as the engine, CPath algorithms are poised to be ready for takeoff and eventual launch into clinical and pharmaceutical orbits. In this paper, we discuss CPath limitations and associated challenges to enable the readers distinguish hope from hype and provide directions for future research to overcome some of the major challenges faced by this budding field to enable its launch into the two orbits.

While state-of-the-art vision transformer models achieve promising results in image classification, they are computationally expensive and require many GFLOPs. Although the GFLOPs of a vision transformer can be decreased by reducing the number of tokens in the network, there is no setting that is optimal for all input images. In this work, we therefore introduce a differentiable parameter-free Adaptive Token Sampler (ATS) module, which can be plugged into any existing vision transformer architecture. ATS empowers vision transformers by scoring and adaptively sampling significant tokens. As a result, the number of tokens is not constant anymore and varies for each input image. By integrating ATS as an additional layer within the current transformer blocks, we can convert them into much more efficient vision transformers with an adaptive number of tokens. Since ATS is a parameter-free module, it can be added to the off-the-shelf pre-trained vision transformers as a plug and play module, thus reducing their GFLOPs without any additional training. Moreover, due to its differentiable design, one can also train a vision transformer equipped with ATS. We evaluate the efficiency of our module in both image and video classification tasks by adding it to multiple SOTA vision transformers. Our proposed module improves the SOTA by reducing their computational costs (GFLOPs) by 2X, while preserving their accuracy on the ImageNet, Kinetics-400, and Kinetics-600 datasets., Comment: ECCV 2022

Nuclear segmentation, classification and quantification within Haematoxylin & Eosin stained histology images enables the extraction of interpretable cell-based features that can be used in downstream explainable models in computational pathology (CPath). However, automatic recognition of different nuclei is faced with a major challenge in that there are several different types of nuclei, some of them exhibiting large intra-class variability. To help drive forward research and innovation for automatic nuclei recognition in CPath, we organise the Colon Nuclei Identification and Counting (CoNIC) Challenge. The challenge encourages researchers to develop algorithms that perform segmentation, classification and counting of nuclei within the current largest known publicly available nuclei-level dataset in CPath, containing around half a million labelled nuclei. Therefore, the CoNIC challenge utilises over 10 times the number of nuclei as the previous largest challenge dataset for nuclei recognition. It is important for algorithms to be robust to input variation if we wish to deploy them in a clinical setting. Therefore, as part of this challenge we will also test the sensitivity of each submitted algorithm to certain input variations.

Many different studies have suggested that episodic memory is a generative process, but most computational models adopt a storage view. In this work, we propose a computational model for generative episodic memory. It is based on the central hypothesis that the hippocampus stores and retrieves selected aspects of an episode as a memory trace, which is necessarily incomplete. At recall, the neocortex reasonably fills in the missing information based on general semantic information in a process we call semantic completion. As episodes we use images of digits (MNIST) augmented by different backgrounds representing context. Our model is based on a VQ-VAE which generates a compressed latent representation in form of an index matrix, which still has some spatial resolution. We assume that attention selects some part of the index matrix while others are discarded, this then represents the gist of the episode and is stored as a memory trace. At recall the missing parts are filled in by a PixelCNN, modeling semantic completion, and the completed index matrix is then decoded into a full image by the VQ-VAE. The model is able to complete missing parts of a memory trace in a semantically plausible way up to the point where it can generate plausible images from scratch. Due to the combinatorics in the index matrix, the model generalizes well to images not trained on. Compression as well as semantic completion contribute to a strong reduction in memory requirements and robustness to noise. Finally we also model an episodic memory experiment and can reproduce that semantically congruent contexts are always recalled better than incongruent ones, high attention levels improve memory accuracy in both cases, and contexts that are not remembered correctly are more often remembered semantically congruently than completely wrong., Comment: 15 pages, 9 figures, 58 references

While recurrent neural networks (RNNs) demonstrate outstanding capabilities for future video frame prediction, they model dynamics in a discrete time space, i.e., they predict the frames sequentially with a fixed temporal step. RNNs are therefore prone to accumulate the error as the number of future frames increases. In contrast, partial differential equations (PDEs) model physical phenomena like dynamics in a continuous time space. However, the estimated PDE for frame forecasting needs to be numerically solved, which is done by discretization of the PDE and diminishes most of the advantages compared to discrete models. In this work, we, therefore, propose to approximate the motion in a video by a continuous function using the Taylor series. To this end, we introduce TaylorSwiftNet, a novel convolutional neural network that learns to estimate the higher order terms of the Taylor series for a given input video. TaylorSwiftNet can swiftly predict future frames in parallel and it allows to change the temporal resolution of the forecast frames on-the-fly. The experimental results on various datasets demonstrate the superiority of our model., Comment: BMVC 2022

Human epidermal growth factor receptor 2 (HER2) is an important prognostic and predictive factor which is overexpressed in 15-20% of breast cancer (BCa). The determination of its status is a key clinical decision making step for selection of treatment regimen and prognostication. HER2 status is evaluated using transcroptomics or immunohistochemistry (IHC) through situ hybridisation (ISH) which require additional costs and tissue burden in addition to analytical variabilities in terms of manual observational biases in scoring. In this study, we propose a novel graph neural network (GNN) based model (termed SlideGraph+) to predict HER2 status directly from whole-slide images of routine Haematoxylin and Eosin (H&E) slides. The network was trained and tested on slides from The Cancer Genome Atlas (TCGA) in addition to two independent test datasets. We demonstrate that the proposed model outperforms the state-of-the-art methods with area under the ROC curve (AUC) values > 0.75 on TCGA and 0.8 on independent test sets. Our experiments show that the proposed approach can be utilised for case triaging as well as pre-ordering diagnostic tests in a diagnostic setting. It can also be used for other weakly supervised prediction problems in computational pathology. The SlideGraph+ code is available at https://github.com/wenqi006/SlideGraph., Comment: 20 pages, 11 figures, 3 tables

Self-supervised video representation methods typically focus on the representation of temporal attributes in videos. However, the role of stationary versus non-stationary attributes is less explored: Stationary features, which remain similar throughout the video, enable the prediction of video-level action classes. Non-stationary features, which represent temporally varying attributes, are more beneficial for downstream tasks involving more fine-grained temporal understanding, such as action segmentation. We argue that a single representation to capture both types of features is sub-optimal, and propose to decompose the representation space into stationary and non-stationary features via contrastive learning from long and short views, i.e. long video sequences and their shorter sub-sequences. Stationary features are shared between the short and long views, while non-stationary features aggregate the short views to match the corresponding long view. To empirically verify our approach, we demonstrate that our stationary features work particularly well on an action recognition downstream task, while our non-stationary features perform better on action segmentation. Furthermore, we analyse the learned representations and find that stationary features capture more temporally stable, static attributes, while non-stationary features encompass more temporally varying ones., Comment: ICCV 2021 (Main Conference)

Automated 3-D breast ultrasound (ABUS) is a newfound system for breast screening that has been proposed as a supplementary modality to mammography for breast cancer detection. While ABUS has better performance in dense breasts, reading ABUS images is exhausting and time-consuming. So, a computer-aided detection system is necessary for interpretation of these images. Mass segmentation plays a vital role in the computer-aided detection systems and it affects the overall performance. Mass segmentation is a challenging task because of the large variety in size, shape, and texture of masses. Moreover, an imbalanced dataset makes segmentation harder. A novel mass segmentation approach based on deep learning is introduced in this paper. The deep network that is used in this study for image segmentation is inspired by U-net, which has been used broadly for dense segmentation in recent years. The system's performance was determined using a dataset of 50 masses including 38 malign and 12 benign lesions. The proposed segmentation method attained a mean Dice of 0.82 which outperformed a two-stage supervised edge-based method with a mean Dice of 0.74 and an adaptive region growing method with a mean Dice of 0.65.

Text detection in natural scene images for content analysis is an interesting task. The research community has seen some great developments for English/Mandarin text detection. However, Urdu text extraction in natural scene images is a task not well addressed. In this work, firstly, a new dataset is introduced for Urdu text in natural scene images. The dataset comprises of 500 standalone images acquired from real scenes. Secondly, the channel enhanced Maximally Stable Extremal Region (MSER) method is applied to extract Urdu text regions as candidates in an image. Two-stage filtering mechanism is applied to eliminate non-candidate regions. In the first stage, text and noise are classified based on their geometric properties. In the second stage, a support vector machine classifier is trained to discard non-text candidate regions. After this, text candidate regions are linked using centroid-based vertical and horizontal distances. Text lines are further analyzed by a different classifier based on HOG features to remove non-text regions. Extensive experimentation is performed on the locally developed dataset to evaluate the performance. The experimental results show good performance on test set images. The dataset will be made available for research use. To the best of our knowledge, the work is the first of its kind for the Urdu language and would provide a good dataset for free research use and serve as a baseline performance on the task of Urdu text extraction.

Most of the recent works on probing representations have focused on BERT, with the presumption that the findings might be similar to the other models. In this work, we extend the probing studies to two other models in the family, namely ELECTRA and XLNet, showing that variations in the pre-training objectives or architectural choices can result in different behaviors in encoding linguistic information in the representations. Most notably, we observe that ELECTRA tends to encode linguistic knowledge in the deeper layers, whereas XLNet instead concentrates that in the earlier layers. Also, the former model undergoes a slight change during fine-tuning, whereas the latter experiences significant adjustments. Moreover, we show that drawing conclusions based on the weight mixing evaluation strategy -- which is widely used in the context of layer-wise probing -- can be misleading given the norm disparity of the representations across different layers. Instead, we adopt an alternative information-theoretic probing with minimum description length, which has recently been proven to provide more reliable and informative results., Comment: Accepted to BlackboxNLP Workshop at EMNLP 2021

The detection of mitotic figures from different scanners/sites remains an important topic of research, owing to its potential in assisting clinicians with tumour grading. The MItosis DOmain Generalization (MIDOG) challenge aims to test the robustness of detection models on unseen data from multiple scanners for this task. We present a short summary of the approach employed by the TIA Centre team to address this challenge. Our approach is based on a hybrid detection model, where mitotic candidates are segmented on stain normalised images, before being refined by a deep learning classifier. Cross-validation on the training images achieved the F1-score of 0.786 and 0.765 on the preliminary test set, demonstrating the generalizability of our model to unseen data from new scanners., Comment: MIDOG challenge at MICCAI 2021

The development of deep segmentation models for computational pathology (CPath) can help foster the investigation of interpretable morphological biomarkers. Yet, there is a major bottleneck in the success of such approaches because supervised deep learning models require an abundance of accurately labelled data. This issue is exacerbated in the field of CPath because the generation of detailed annotations usually demands the input of a pathologist to be able to distinguish between different tissue constructs and nuclei. Manually labelling nuclei may not be a feasible approach for collecting large-scale annotated datasets, especially when a single image region can contain thousands of different cells. However, solely relying on automatic generation of annotations will limit the accuracy and reliability of ground truth. Therefore, to help overcome the above challenges, we propose a multi-stage annotation pipeline to enable the collection of large-scale datasets for histology image analysis, with pathologist-in-the-loop refinement steps. Using this pipeline, we generate the largest known nuclear instance segmentation and classification dataset, containing nearly half a million labelled nuclei in H&E stained colon tissue. We have released the dataset and encourage the research community to utilise it to drive forward the development of downstream cell-based models in CPath.

"Is it possible to predict expression levels of different genes at a given spatial location in the routine histology image of a tumor section by modeling its stain absorption characteristics?" In this work, we propose a "stain-aware" machine learning approach for prediction of spatial transcriptomic gene expression profiles using digital pathology image of a routine Hematoxylin & Eosin (H&E) histology section. Unlike recent deep learning methods which are used for gene expression prediction, our proposed approach termed Neural Stain Learning (NSL) explicitly models the association of stain absorption characteristics of the tissue with gene expression patterns in spatial transcriptomics by learning a problem-specific stain deconvolution matrix in an end-to-end manner. The proposed method with only 11 trainable weight parameters outperforms both classical regression models with cellular composition and morphological features as well as deep learning methods. We have found that the gene expression predictions from the proposed approach show higher correlations with true expression values obtained through sequencing for a larger set of genes in comparison to other approaches., Comment: 14 pages, 4 figures, 1 table