Towards Deep Cellular Phenotyping in Placental HistologyMichael Ferlaino, Craig A. Glastonbury, Carolina Motta-Mejia et al.
The placenta is a complex organ, playing multiple roles during fetal development. Very little is known about the association between placental morphological abnormalities and fetal physiology. In this work, we present an open sourced, computationally tractable deep learning pipeline to analyse placenta histology at the level of the cell. By utilising two deep Convolutional Neural Network architectures and transfer learning, we can robustly localise and classify placental cells within five classes with an accuracy of 89%. Furthermore, we learn deep embeddings encoding phenotypic knowledge that is capable of both stratifying five distinct cell populations and learn intraclass phenotypic variance. We envisage that the automation of this pipeline to population scale studies of placenta histology has the potential to improve our understanding of basic cellular placental biology and its variations, particularly its role in predicting adverse birth outcomes.
Contrastive Mixture of Posteriors for Counterfactual Inference, Data Integration and FairnessAdam Foster, Árpi Vezér, Craig A Glastonbury et al.
Learning meaningful representations of data that can address challenges such as batch effect correction and counterfactual inference is a central problem in many domains including computational biology. Adopting a Conditional VAE framework, we show that marginal independence between the representation and a condition variable plays a key role in both of these challenges. We propose the Contrastive Mixture of Posteriors (CoMP) method that uses a novel misalignment penalty defined in terms of mixtures of the variational posteriors to enforce this independence in latent space. We show that CoMP has attractive theoretical properties compared to previous approaches, and we prove counterfactual identifiability of CoMP under additional assumptions. We demonstrate state-of-the-art performance on a set of challenging tasks including aligning human tumour samples with cancer cell-lines, predicting transcriptome-level perturbation responses, and batch correction on single-cell RNA sequencing data. We also find parallels to fair representation learning and demonstrate that CoMP is competitive on a common task in the field.
Adjusting for Confounding in Unsupervised Latent Representations of ImagesCraig A. Glastonbury, Michael Ferlaino, Christoffer Nellåker et al.
Biological imaging data are often partially confounded or contain unwanted variability. Examples of such phenomena include variable lighting across microscopy image captures, stain intensity variation in histological slides, and batch effects for high throughput drug screening assays. Therefore, to develop "fair" models which generalise well to unseen examples, it is crucial to learn data representations that are insensitive to nuisance factors of variation. In this paper, we present a strategy based on adversarial training, capable of learning unsupervised representations invariant to confounders. As an empirical validation of our method, we use deep convolutional autoencoders to learn unbiased cellular representations from microscopy imaging.
Count-ception: Counting by Fully Convolutional Redundant CountingJoseph Paul Cohen, Genevieve Boucher, Craig A. Glastonbury et al.
Counting objects in digital images is a process that should be replaced by machines. This tedious task is time consuming and prone to errors due to fatigue of human annotators. The goal is to have a system that takes as input an image and returns a count of the objects inside and justification for the prediction in the form of object localization. We repose a problem, originally posed by Lempitsky and Zisserman, to instead predict a count map which contains redundant counts based on the receptive field of a smaller regression network. The regression network predicts a count of the objects that exist inside this frame. By processing the image in a fully convolutional way each pixel is going to be accounted for some number of times, the number of windows which include it, which is the size of each window, (i.e., 32x32 = 1024). To recover the true count we take the average over the redundant predictions. Our contribution is redundant counting instead of predicting a density map in order to average over errors. We also propose a novel deep neural network architecture adapted from the Inception family of networks called the Count-ception network. Together our approach results in a 20% relative improvement (2.9 to 2.3 MAE) over the state of the art method by Xie, Noble, and Zisserman in 2016.