How healthy am I? My immunome knows the score. Groundbreaking new tests reveal patterns in our immune systems that can signal underlying disease and tell us how well we might recover from our next cold. I got my results in a text message. It's not often you get a text about the robustness of your immune system, but that's what popped up on my phone last spring. Sent by John Tsang, an immunologist at Yale, the text came after his lab had put my blood through a mind-boggling array of newfangled tests. The result--think of it as a full-body, high-resolution CT scan of my immune system--would reveal more about the state of my health than any test I had ever taken. And it could potentially tell me far more than I wanted to know. "David," the text read, "you are the red dot." Tsang was referring to an image he had attached to the text that showed a graph with a scattering of black dots representing other people whose immune systems had been evaluated--and a lone red one.

Label-free imaging has gained broad interest because of its potential to omit elaborate staining procedures which is especially relevant for in vivo use. Label-free multiphoton microscopy (MPM), for instance, exploits two-photon excitation of natural autofluorescence (AF) from native, metabolic proteins, making it ideal for in vivo endomicroscopy. Deep learning (DL) models have been widely used in other optical imaging technologies to predict specific target annotations and thereby digitally augment the specificity of these label-free images. However, this computational specificity has only rarely been implemented for MPM. In this work, we used a data set of label-free MPM images from a series of different immune cell types (5,075 individual cells for binary classification in mixed samples and 3,424 cells for a multi-class classification task) and trained a convolutional neural network (CNN) to classify cell types based on this label-free AF as input. A low-complexity squeezeNet architecture was able to achieve reliable immune cell classification results (0.89 ROC-AUC, 0.95 PR-AUC, for binary classification in mixed samples; 0.689 F1 score, 0.697 precision, 0.748 recall, and 0.683 MCC for six-class classification in isolated samples). Perturbation tests confirmed that the model is not confused by extracellular environment and that both input AF channels (NADH and FAD) are about equally important to the classification. In the future, such predictive DL models could directly detect specific immune cells in unstained images and thus, computationally improve the specificity of label-free MPM which would have great potential for in vivo endomicroscopy.

Graph Neural Networks (GNNs) have recently been found to excel in histopathology. However, an important histopathological task, where GNNs have not been extensively explored, is the classification of glomeruli health as an important indicator in nephropathology. This task presents unique difficulties, particularly for the graph construction, i.e., the identification of nodes, edges, and informative features. In this work, we propose a pipeline composed of different traditional and machine learning-based computer vision techniques to identify nodes, edges, and their corresponding features to form a heterogeneous graph. We then proceed to propose a novel heterogeneous GNN architecture for glomeruli classification, called HIEGNet, that integrates both glomeruli and their surrounding immune cells. Hence, HIEGNet is able to consider the immune environment of each glomerulus in its classification. Our HIEGNet was trained and tested on a dataset of Whole Slide Images from kidney transplant patients. Experimental results demonstrate that HIEGNet outperforms several baseline models and generalises best between patients among all baseline models.

In this paper, we adapt a two species agent-based cancer model that describes the interaction between cancer cells and healthy cells on a uniform grid to include the interaction with a third species -- namely immune cells. We run six different scenarios to explore the competition between cancer and immune cells and the initial concentration of the immune cells on cancer dynamics. We then use coupled equation learning to construct a population-based reaction model for each scenario. We show how they can be unified into a single surrogate population-based reaction model, whose underlying three coupled ordinary differential equations are much easier to analyse than the original agent-based model. As an example, by finding the single steady state of the cancer concentration, we are able to find a linear relationship between this concentration and the initial concentration of the immune cells. This then enables us to estimate suitable values for the competition and initial concentration to reduce the cancer substantially without performing additional complex and expensive simulations from an agent-based stochastic model. The work shows the importance of performing equation learning from agent-based stochastic data for gaining key insights about the behaviour of complex cellular dynamics.

With the advent of novel cancer treatment options such as immunotherapy, studying the tumour immune micro-environment is crucial to inform on prognosis and understand response to therapeutic agents. A key approach to characterising the tumour immune micro-environment may be through combining (1) digitised microscopic high-resolution optical images of hematoxylin and eosin (H&E) stained tissue sections obtained in routine histopathology examinations with (2) automated immune cell detection and classification methods. However, current individual immune cell classification models for digital pathology present relatively poor performance. This is mainly due to the limited size of currently available datasets of individual immune cells, a consequence of the time-consuming and difficult problem of manually annotating immune cells on digitised H&E whole slide images. In that context, we introduce Immunocto, a massive, multi-million automatically generated database of 6,848,454 human cells, including 2,282,818 immune cells distributed across 4 subtypes: CD4$^+$ T cell lymphocytes, CD8$^+$ T cell lymphocytes, B cell lymphocytes, and macrophages. For each cell, we provide a 64$\times$64 pixels H&E image at $\mathbf{40}\times$ magnification, along with a binary mask of the nucleus and a label. To create Immunocto, we combined open-source models and data to automatically generate the majority of contours and labels. The cells are obtained from a matched H&E and immunofluorescence colorectal dataset from the Orion platform, while contours are obtained using the Segment Anything Model. A classifier trained on H&E images from Immunocto produces an average F1 score of 0.74 to differentiate the 4 immune cell subtypes and other cells. Immunocto can be downloaded at: https://zenodo.org/uploads/11073373.

Cancer is one of the most widespread diseases around the world with millions of new patients each year. Bladder cancer is one of the most prevalent types of cancer affecting all individuals alike with no obvious prototypical patient. The current standard treatment for BC follows a routine weekly Bacillus Calmette-Guerin (BCG) immunotherapy-based therapy protocol which is applied to all patients alike. The clinical outcomes associated with BCG treatment vary significantly among patients due to the biological and clinical complexity of the interaction between the immune system, treatments, and cancer cells. In this study, we take advantage of the patient's socio-demographics to offer a personalized mathematical model that describes the clinical dynamics associated with BCG-based treatment. To this end, we adopt a well-established BCG treatment model and integrate a machine learning component to temporally adjust and reconfigure key parameters within the model thus promoting its personalization. Using real clinical data, we show that our personalized model favorably compares with the original one in predicting the number of cancer cells at the end of the treatment, with 14.8% improvement, on average.

Vaccines are biological preparations that help to provide immunity against infectious diseases. They work by introducing a weakened or dead form of a disease-causing organism, or a piece of its genetic material, into the body. This triggers an immune response, which helps the body recognize and remember the pathogen if it infects the body again in the future. As a result, the body can quickly produce an immune response, which helps to prevent the disease from developing or reduces its severity. A Chinese research team has made a breakthrough in vaccine development by using computer-aided molecular design and machine learning to create two innovative adjuvants, which are substances added to vaccines to enhance the immune response.

Cancer is a disease characterized by the abnormal growth and division of cells in the body. Tumors can affect any part of the body and can be benign (non-cancerous) or malignant (cancerous), spreading to other parts of the body through the bloodstream or lymph system. Scientists at the University of California, San Francisco (UCSF) and IBM Research have created a virtual library of thousands of "command sentences" for cells using machine learning. These "sentences" are based on combinations of "words" that direct engineered immune cells to find and continuously eliminate cancer cells. This research, which was recently published in the journal Science, is the first time that advanced computational techniques have been applied to a field that has traditionally progressed through trial-and-error experimentation and the use of pre-existing molecules rather than synthetic ones to engineer cells.

Using new machine learning techniques, researchers at UC San Francisco (UCSF), in collaboration with a team at IBM Research, have developed a virtual molecular library of thousands of "command sentences" for cells, based on combinations of "words" that guided engineered immune cells to seek out and tirelessly kill cancer cells. The work, published online Dec. 8, 2022, in Science, represents the first time such sophisticated computational approaches have been applied to a field that, until now, has progressed largely through ad hoc tinkering and engineering cells with existing, rather than synthesized, molecules. The advance allows scientists to predict which elements -- natural or synthesized -- they should include in a cell to give it the precise behaviors required to respond effectively to complex diseases. "This is a vital shift for the field," said Wendell Lim, PhD, the Byers Distinguished Professor of Cellular and Molecular Pharmacology, who directs the UCSF Cell Design Institute and led the study. "Only by having that power of prediction can we get to a place where we can rapidly design new cellular therapies that carry out the desired activities."

Using new machine learning techniques, researchers at UC San Francisco (UCSF), in collaboration with a team at IBM Research, have developed a virtual molecular library of thousands of "command sentences" for cells, based on combinations of "words" that guided engineered immune cells to seek out and tirelessly kill cancer cells. The work, published online Dec. 8, 2022, in Science, represents the first time such sophisticated computational approaches have been applied to a field that until now has progressed largely through ad hoc tinkering and engineering cells with existing--rather than synthesized--molecules. The advance allows scientists to predict which elements--natural or synthesized--they should include in a cell to give it the precise behaviors required to respond effectively to complex diseases. "This is a vital shift for the field," said Wendell Lim, Ph.D., the Byers Distinguished Professor of Cellular and Molecular Pharmacology, who directs the UCSF Cell Design Institute and led the study. "Only by having that power of prediction can we get to a place where we can rapidly design new cellular therapies that carry out the desired activities."