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Fayyaz Minhas

Publications and source records attributed to Fayyaz Minhas.

33 records · Page 2Linked to original sources

REET: Robustness Evaluation and Enhancement Toolbox for Computational Pathology

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

cs.LG↗

Insights into performance evaluation of com-pound-protein interaction prediction methods

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

q-bio.QM↗

Towards Launching AI Algorithms for Cellular Pathology into Clinical & Pharmaceutical Orbits

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.

eess.IV↗

Lizard: A Large-Scale Dataset for Colonic Nuclear Instance Segmentation and Classification

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.

cs.CV↗

CoNIC: Colon Nuclei Identification and Counting Challenge 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.

cs.CV↗

SlideGraph+: Whole Slide Image Level Graphs to Predict HER2Status in Breast Cancer

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.

cs.CV↗

Stain-Robust Mitotic Figure Detection for the Mitosis Domain Generalization Challenge

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.

cs.CV↗

L1-regularized neural ranking for risk stratification and its application to prediction of time to distant metastasis in luminal node negative chemotherapy naïve breast cancer patients

Can we predict if an early stage cancer patient is at high risk of developing distant metastasis and what clinicopathological factors are associated with such a risk? In this paper, we propose a ranking based censoring-aware machine learning model for answering such questions. The proposed model is able to generate an interpretable formula for risk stratifi-cation using a minimal number of clinicopathological covariates through L1-regulrization. Using this approach, we analyze the association of time to distant metastasis (TTDM) with various clinical parameters for early stage, luminal (ER+ or HER2-) breast cancer patients who received endocrine therapy but no chemotherapy (n = 728). The TTDM risk stratification formula obtained using the proposed approach is primarily based on mitotic score, histolog-ical tumor type and lymphovascular invasion. These findings corroborate with the known role of these covariates in increased risk for distant metastasis. Our analysis shows that the proposed risk stratification formula can discriminate between cases with high and low risk of distant metastasis (p-value < 0.005) and can also rank cases based on their time to distant metastasis with a concordance-index of 0.73.

cs.LG↗

Semantic annotation for computational pathology: Multidisciplinary experience and best practice recommendations

Recent advances in whole slide imaging (WSI) technology have led to the development of a myriad of computer vision and artificial intelligence (AI) based diagnostic, prognostic, and predictive algorithms. Computational Pathology (CPath) offers an integrated solution to utilize information embedded in pathology WSIs beyond what we obtain through visual assessment. For automated analysis of WSIs and validation of machine learning (ML) models, annotations at the slide, tissue and cellular levels are required. The annotation of important visual constructs in pathology images is an important component of CPath projects. Improper annotations can result in algorithms which are hard to interpret and can potentially produce inaccurate and inconsistent results. Despite the crucial role of annotations in CPath projects, there are no well-defined guidelines or best practices on how annotations should be carried out. In this paper, we address this shortcoming by presenting the experience and best practices acquired during the execution of a large-scale annotation exercise involving a multidisciplinary team of pathologists, ML experts and researchers as part of the Pathology image data Lake for Analytics, Knowledge and Education (PathLAKE) consortium. We present a real-world case study along with examples of different types of annotations, diagnostic algorithm, annotation data dictionary and annotation constructs. The analyses reported in this work highlight best practice recommendations that can be used as annotation guidelines over the lifecycle of a CPath project.

eess.IV↗

Now You See It, Now You Dont: Adversarial Vulnerabilities in Computational Pathology

Deep learning models are routinely employed in computational pathology (CPath) for solving problems of diagnostic and prognostic significance. Typically, the generalization performance of CPath models is analyzed using evaluation protocols such as cross-validation and testing on multi-centric cohorts. However, to ensure that such CPath solutions are robust and safe for use in a clinical setting, a critical analysis of their predictive performance and vulnerability to adversarial attacks is required, which is the focus of this paper. Specifically, we show that a highly accurate model for classification of tumour patches in pathology images (AUC > 0.95) can easily be attacked with minimal perturbations which are imperceptible to lay humans and trained pathologists alike. Our analytical results show that it is possible to generate single-instance white-box attacks on specific input images with high success rate and low perturbation energy. Furthermore, we have also generated a single universal perturbation matrix using the training dataset only which, when added to unseen test images, results in forcing the trained neural network to flip its prediction labels with high confidence at a success rate of > 84%. We systematically analyze the relationship between perturbation energy of an adversarial attack, its impact on morphological constructs of clinical significance, their perceptibility by a trained pathologist and saliency maps obtained using deep learning models. Based on our analysis, we strongly recommend that computational pathology models be critically analyzed using the proposed adversarial validation strategy prior to clinical adoption.

eess.IV↗

SAFRON: Stitching Across the Frontier for Generating Colorectal Cancer Histology Images

Synthetic images can be used for the development and evaluation of deep learning algorithms in the context of limited availability of data. In the field of computational pathology, where histology images are large in size and visual context is crucial, synthesis of large high resolution images via generative modeling is a challenging task. This is due to memory and computational constraints hindering the generation of large images. To address this challenge, we propose a novel SAFRON (Stitching Across the FRONtiers) framework to construct realistic, large high resolution tissue image tiles from ground truth annotations while preserving morphological features and with minimal boundary artifacts. We show that the proposed method can generate realistic image tiles of arbitrarily large size after training it on relatively small image patches. We demonstrate that our model can generate high quality images, both visually and in terms of the Frechet Inception Distance. Compared to other existing approaches, our framework is efficient in terms of the memory requirements for training and also in terms of the number of computations to construct a large high-resolution image. We also show that training on synthetic data generated by SAFRON can significantly boost the performance of a state-of-the-art algorithm for gland segmentation in colorectal cancer histology images. Sample high resolution images generated using SAFRON are available at the URL: https://warwick.ac.uk/TIALab/SAFRON

eess.IV↗

Elementary Effects Analysis of factors controlling COVID-19 infections in computational simulation reveals the importance of Social Distancing and Mask Usage

COVID-19 was declared a pandemic by the World Health Organization (WHO) on March 11th, 2020. With half of the world's countries in lockdown as of April due to this pandemic, monitoring and understanding the spread of the virus and infection rates and how these factors relate to behavioural and societal parameters is crucial for effective policy making. This paper aims to investigate the effectiveness of masks, social distancing, lockdown and self-isolation for reducing the spread of SARS-CoV-2 infections. Our findings based on agent-based simulation modelling show that whilst requiring a lockdown is widely believed to be the most efficient method to quickly reduce infection numbers, the practice of social distancing and the usage of surgical masks can potentially be more effective than requiring a lockdown. Our multivariate analysis of simulation results using the Morris Elementary Effects Method suggests that if a sufficient proportion of the population wore surgical masks and followed social distancing regulations, then SARS-CoV-2 infections can be controlled without requiring a lockdown.

cs.AI↗

AMP0: Species-Specific Prediction of Anti-microbial Peptides using Zero and Few Shot Learning

The evolution of drug-resistant microbial species is one of the major challenges to global health. The development of new antimicrobial treatments such as antimicrobial peptides needs to be accelerated to combat this threat. However, the discovery of novel antimicrobial peptides is hampered by low-throughput biochemical assays. Computational techniques can be used for rapid screening of promising antimicrobial peptide candidates prior to testing in the wet lab. The vast majority of existing antimicrobial peptide predictors are non-targeted in nature, i.e., they can predict whether a given peptide sequence is antimicrobial, but they are unable to predict whether the sequence can target a particular microbial species. In this work, we have developed a targeted antimicrobial peptide activity predictor that can predict whether a peptide is effective against a given microbial species or not. This has been made possible through zero-shot and few-shot machine learning. The proposed predictor called AMP0 takes in the peptide amino acid sequence and any N/C-termini modifications together with the genomic sequence of a target microbial species to generate targeted predictions. It is important to note that the proposed method can generate predictions for species that are not part of its training set. The accuracy of predictions for novel test species can be further improved by providing a few example peptides for that species. Our computational cross-validation results show that the pro-posed scheme is particularly effective for targeted antimicrobial prediction in comparison to existing approaches and can be used for screening potential antimicrobial peptides in a targeted manner especially for cases in which the number of training examples is small. The webserver of the method is available at http://ampzero.pythonanywhere.com.

q-bio.BM↗

Ten ways to fool the masses with machine learning

If you want to tell people the truth, make them laugh, otherwise they'll kill you. (source unclear) Machine learning and deep learning are the technologies of the day for developing intelligent automatic systems. However, a key hurdle for progress in the field is the literature itself: we often encounter papers that report results that are difficult to reconstruct or reproduce, results that mis-represent the performance of the system, or contain other biases that limit their validity. In this semi-humorous article, we discuss issues that arise in running and reporting results of machine learning experiments. The purpose of the article is to provide a list of watch out points for researchers to be aware of when developing machine learning models or writing and reviewing machine learning papers.

cs.LG↗

Machine Learning with Abstention for Automated Liver Disease Diagnosis

This paper presents a novel approach for detection of liver abnormalities in an automated manner using ultrasound images. For this purpose, we have implemented a machine learning model that can not only generate labels (normal and abnormal) for a given ultrasound image but it can also detect when its prediction is likely to be incorrect. The proposed model abstains from generating the label of a test example if it is not confident about its prediction. Such behavior is commonly practiced by medical doctors who, when given insufficient information or a difficult case, can chose to carry out further clinical or diagnostic tests before generating a diagnosis. However, existing machine learning models are designed in a way to always generate a label for a given example even when the confidence of their prediction is low. We have proposed a novel stochastic gradient based solver for the learning with abstention paradigm and use it to make a practical, state of the art method for liver disease classification. The proposed method has been benchmarked on a data set of approximately 100 patients from MINAR, Multan, Pakistan and our results show that the proposed scheme offers state of the art classification performance.

cs.LG↗