Amina Asif

Mohsin Bilal, Robert Jewsbury, Ruoyu Wang et al.

Image analysis and machine learning algorithms operating on multi-gigapixel whole-slide images (WSIs) often process a large number of tiles (sub-images) and require aggregating predictions from the tiles in order to predict WSI-level labels. In this paper, we present a review of existing literature on various types of aggregation methods with a view to help guide future research in the area of computational pathology (CPath). We propose a general CPath workflow with three pathways that consider multiple levels and types of data and the nature of computation to analyse WSIs for predictive modelling. We categorize aggregation methods according to the context and representation of the data, features of computational modules and CPath use cases. We compare and contrast different methods based on the principle of multiple instance learning, perhaps the most commonly used aggregation method, covering a wide range of CPath literature. To provide a fair comparison, we consider a specific WSI-level prediction task and compare various aggregation methods for that task. Finally, we conclude with a list of objectives and desirable attributes of aggregation methods in general, pros and cons of the various approaches, some recommendations and possible future directions.

Ruoyu Wang, Syed Ali Khurram, Amina Asif et al.

The aetiology of head and neck squamous cell carcinoma (HNSCC) involves multiple carcinogens such as alcohol, tobacco and infection with human papillomavirus (HPV). As the HPV infection influences the prognosis, treatment and survival of patients with HNSCC, it is important to determine the HPV status of these tumours. In this paper, we propose a novel triplet-ranking loss function and a multiple instance learning pipeline for HPV status prediction. This achieves a new state-of-the-art performance in HPV detection using only the routine H&E stained WSIs on two HNSCC cohorts. Furthermore, a comprehensive tumour microenvironment profiling was performed, which characterised the unique patterns between HPV+/- HNSCC from genomic, immunology and cellular perspectives. Positive correlations of the proposed score with different subtypes of T cells (e.g. T cells follicular helper, CD8+ T cells), and negative correlations with macrophages and connective cells (e.g. fibroblast) were identified, which is in line with clinical findings. Unique gene expression profiles were also identified with respect to HPV infection status, and is in line with existing findings.

Alex Foote, Amina Asif, Nasir Rajpoot et al.

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

Fayyaz ul Amir Afsar Minhas, Amina Asif

An artificial neuron is modelled as a weighted summation followed by an activation function which determines its output. A wide variety of activation functions such as rectified linear units (ReLU), leaky-ReLU, Swish, MISH, etc. have been explored in the literature. In this short paper, we explore what happens when the activation function of each neuron in an artificial neural network is learned natively from data alone. This is achieved by modelling the activation function of each neuron as a small neural network whose weights are shared by all neurons in the original network. We list our primary findings in the conclusions section. The code for our analysis is available at: https://github.com/amina01/Learning-Neural-Activations.

Amina Asif, Fayyaz ul Amir Afsar Minhas

Multiple Instance Learning (MIL) is a weak supervision learning paradigm that allows modeling of machine learning problems in which labels are available only for groups of examples called bags. A positive bag may contain one or more positive examples but it is not known which examples in the bag are positive. All examples in a negative bag belong to the negative class. Such problems arise frequently in fields of computer vision, medical image processing and bioinformatics. Many neural network based solutions have been proposed in the literature for MIL, however, almost all of them rely on introducing specialized blocks and connectivity in the architectures. In this paper, we present a novel and effective approach to Multiple Instance Learning in neural networks. Instead of making changes to the architectures, we propose a simple bag-level ranking loss function that allows Multiple Instance Classification in any neural architecture. We have demonstrated the effectiveness of our proposed method for popular MIL benchmark datasets. In addition, we have tested the performance of our method in convolutional neural networks used to model an MIL problem derived from the well-known MNIST dataset. Results have shown that despite being simpler, our proposed scheme is comparable or better than existing methods in the literature in practical scenarios. Python code files for all the experiments can be found at https://github.com/amina01/ESMIL.

Amina Asif, Kashif Rajpoot, David Snead et al.

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.

Alex Foote, Amina Asif, Ayesha Azam et al.

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.

Amina Asif, Fayyaz ul Amir Afsar Minhas

Learning with rejection (LWR) allows development of machine learning systems with the ability to discard low confidence decisions generated by a prediction model. That is, just like human experts, LWR allows machine models to abstain from generating a prediction when reliability of the prediction is expected to be low. Several frameworks for this learning with rejection have been proposed in the literature. However, most of them work for classification problems only and regression with rejection has not been studied in much detail. In this work, we present a neural framework for LWR based on a generalized meta-loss function that involves simultaneous training of two neural network models: a predictor model for generating predictions and a rejecter model for deciding whether the prediction should be accepted or rejected. The proposed framework can be used for classification as well as regression and other related machine learning tasks. We have demonstrated the applicability and effectiveness of the method on synthetically generated data as well as benchmark datasets from UCI machine learning repository for both classification and regression problems. Despite being simpler in implementation, the proposed scheme for learning with rejection has shown to perform at par or better than previously proposed methods. Furthermore, we have applied the method to the problem of hurricane intensity prediction from satellite imagery. Significant improvement in performance as compared to conventional supervised methods shows the effectiveness of the proposed scheme in real-world regression problems.

Fayyaz Minhas, Amina Asif, Asa Ben-Hur

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.

Amina Asif, Muhammad Dawood, Fayyaz ul Amir Afsar Minhas

Learning using privileged information (LUPI) is a powerful heterogenous feature space machine learning framework that allows a machine learning model to learn from highly informative or privileged features which are available during training only to generate test predictions using input space features which are available both during training and testing. LUPI can significantly improve prediction performance in a variety of machine learning problems. However, existing large margin and neural network implementations of learning using privileged information are mostly designed for classification tasks. In this work, we have proposed a simple yet effective formulation that allows us to perform regression using privileged information through a custom loss function. Apart from regression, our formulation allows general application of LUPI to classification and other related problems as well. We have verified the correctness, applicability and effectiveness of our method on regression and classification problems over different synthetic and real-world problems. To test the usefulness of the proposed model in real-world problems, we have evaluated our method on the problem of protein binding affinity prediction. The proposed LUPI regression-based model has shown to outperform the current state-of-the-art predictor.

Kanza Hamid, Amina Asif, Wajid Abbasi et al.

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.

Abdul Hannan Basit, Wajid Arshad Abbasi, Amina Asif et al.

Detection of protein-protein interactions (PPIs) plays a vital role in molecular biology. Particularly, infections are caused by the interactions of host and pathogen proteins. It is important to identify host-pathogen interactions (HPIs) to discover new drugs to counter infectious diseases. Conventional wet lab PPI prediction techniques have limitations in terms of large scale application and budget. Hence, computational approaches are developed to predict PPIs. This study aims to develop large margin machine learning models to predict interspecies PPIs with a special interest in host-pathogen protein interactions (HPIs). Especially, we focus on seeking answers to three queries that arise while developing an HPI predictor. 1) How should we select negative samples? 2) What should be the size of negative samples as compared to the positive samples? 3) What type of margin violation penalty should be used to train the predictor? We compare two available methods for negative sampling. Moreover, we propose a new method of assigning weights to each training example in weighted SVM depending on the distance of the negative examples from the positive examples. We have also developed a web server for our HPI predictor called HoPItor (Host Pathogen Interaction predicTOR) that can predict interactions between human and viral proteins. This webserver can be accessed at the URL: http://faculty.pieas.edu.pk/fayyaz/software.html#HoPItor.

Amina Asif, Wajid Arshad Abbasi, Farzeen Munir et al.

Motivation: A major challenge in the development of machine learning based methods in computational biology is that data may not be accurately labeled due to the time and resources required for experimentally annotating properties of proteins and DNA sequences. Standard supervised learning algorithms assume accurate instance-level labeling of training data. Multiple instance learning is a paradigm for handling such labeling ambiguities. However, the widely used large-margin classification methods for multiple instance learning are heuristic in nature with high computational requirements. In this paper, we present stochastic sub-gradient optimization large margin algorithms for multiple instance classification and ranking, and provide them in a software suite called pyLEMMINGS. Results: We have tested pyLEMMINGS on a number of bioinformatics problems as well as benchmark datasets. pyLEMMINGS has successfully been able to identify functionally important segments of proteins: binding sites in Calmodulin binding proteins, prion forming regions, and amyloid cores. pyLEMMINGS achieves state-of-the-art performance in all these tasks, demonstrating the value of multiple instance learning. Furthermore, our method has shown more than 100-fold improvement in terms of running time as compared to heuristic solutions with improved accuracy over benchmark datasets. Availability and Implementation: pyLEMMINGS python package is available for download at: http://faculty.pieas.edu.pk/fayyaz/software.html#pylemmings.