Deformable templates, or atlases, are images that represent a prototypical anatomy for a population, and are often enhanced with probabilistic anatomical label maps. They are commonly used in medical image analysis for population studies and computational anatomy tasks such as registration and segmentation. Because developing a template is a computationally expensive process, relatively few templates are available. As a result, analysis is often conducted with sub-optimal templates that are not truly representative of the study population, especially when there are large variations within this population. We propose a machine learning framework that uses convolutional registration neural networks to efficiently learn a function that outputs templates conditioned on subject-specific attributes, such as age and sex. We also leverage segmentations, when available, to produce anatomical segmentation maps for the resulting templates. The learned network can also be used to register subject images to the templates. We demonstrate our method on a compilation of 3D brain MRI datasets, and show that it can learn high-quality templates that are representative of populations. We find that annotated conditional templates enable better registration than their unlabeled unconditional counterparts, and outperform other templates construction methods.

We present MultiMorph, a fast and efficient method for constructing anatomical atlases on the fly. Atlases capture the canonical structure of a collection of images and are essential for quantifying anatomical variability across populations. However, current atlas construction methods often require days to weeks of computation, thereby discouraging rapid experimentation. As a result, many scientific studies rely on suboptimal, precomputed atlases from mismatched populations, negatively impacting downstream analyses. MultiMorph addresses these challenges with a feedforward model that rapidly produces high-quality, population-specific atlases in a single forward pass for any 3D brain dataset, without any fine-tuning or optimization. MultiMorph is based on a linear group-interaction layer that aggregates and shares features within the group of input images. Further, by leveraging auxiliary synthetic data, MultiMorph generalizes to new imaging modalities and population groups at test-time. Experimentally, MultiMorph outperforms state-of-the-art optimization-based and learning-based atlas construction methods in both small and large population settings, with a 100-fold reduction in time. This makes MultiMorph an accessible framework for biomedical researchers without machine learning expertise, enabling rapid, high-quality atlas generation for diverse studies.

Medical researchers and clinicians often need to perform novel segmentation tasks on a set of related images. Existing methods for segmenting a new dataset are either interactive, requiring substantial human effort for each image, or require an existing set of previously labeled images. We introduce a system, MultiverSeg, that enables practitioners to rapidly segment an entire new dataset without requiring access to any existing labeled data from that task or domain. Along with the image to segment, the model takes user interactions such as clicks, bounding boxes or scribbles as input, and predicts a segmentation. As the user segments more images, those images and segmentations become additional inputs to the model, providing context. As the context set of labeled images grows, the number of interactions required to segment each new image decreases. We demonstrate that MultiverSeg enables users to interactively segment new datasets efficiently, by amortizing the number of interactions per image to achieve an accurate segmentation. Compared to using a state-of-the-art interactive segmentation method, MultiverSeg reduced the total number of clicks by 36% and scribble steps by 25% to achieve 90% Dice on sets of images from unseen tasks. We release code and model weights at https://multiverseg.csail.mit.edu

Current volumetric biomedical foundation models struggle to generalize as public 3D datasets are small and do not cover the broad diversity of medical procedures, conditions, anatomical regions, and imaging protocols. We address this by creating a representation learning method that instead anticipates strong domain shifts at training time itself. We first propose a data engine that synthesizes highly variable training samples that would enable generalization to new biomedical contexts. To then train a single 3D network for any voxel-level task, we develop a contrastive learning method that pretrains the network to be stable against nuisance imaging variation simulated by the data engine, a key inductive bias for generalization. This network's features can be used as robust representations of input images for downstream tasks and its weights provide a strong, _dataset-agnostic_ initialization for finetuning on new datasets. As a result, we set new standards across _both_ multimodality registration and few-shot segmentation, a first for any 3D biomedical vision model, all without (pre-)training on any existing dataset of real images.

A single biomedical image can be segmented in multiple valid ways, depending on the application. For instance, a brain MRI may be divided according to tissue types, vascular territories, broad anatomical regions, fine-grained anatomy, or pathology. Existing automatic segmentation models typically either (1) support only a single protocol---the one they were trained on---or (2) require labor-intensive prompting to specify the desired segmentation. We introduce _Pancakes_, a framework that, given a new image from a previously unseen domain, automatically generates multi-label segmentation maps for _multiple_ plausible protocols, while maintaining semantic consistency across related images. In extensive experiments across seven previously unseen domains, _Pancakes_ consistently outperforms strong baselines, often by a wide margin, demonstrating its ability to produce diverse yet coherent segmentation maps on unseen domains.

Learning-based image reconstruction models, such as those based on the U-Net, require a large set of labeled images if good generalization is to be guaranteed. In some imaging domains, however, labeled data with pixel- or voxel-level label accuracy are scarce due to the cost of acquiring them. This problem is exacerbated further in domains like medical imaging, where there is no single ground truth label, resulting in large amounts of repeat variability in the labels. Therefore, training reconstruction networks to generalize better by learning from both labeled and unlabeled examples (called semi-supervised learning) is problem of practical and theoretical interest. However, traditional semi-supervised learning methods for image reconstruction often necessitate handcrafting a differentiable regularizer specific to some given imaging problem, which can be extremely time-consuming. In this work, we propose "supervision by denoising" (SUD), a framework to supervise reconstruction models using their own denoised output as labels. SUD unifies stochastic averaging and spatial denoising techniques under a spatio-temporal denoising framework and alternates denoising and model weight update steps in an optimization framework for semi-supervision. As example applications, we apply SUD to two problems from biomedical imaging-anatomical brain reconstruction (3D) and cortical parcellation (2D)-to demonstrate a significant improvement in reconstruction over supervised-only and ensembling baselines.

Existing learning-based solutions to medical image segmentation have two important shortcomings. First, for most new segmentation tasks, a new model has to be trained or fine-tuned. This requires extensive resources and machine-learning expertise, and is therefore often infeasible for medical researchers and clinicians. Second, most existing segmentation methods produce a single deterministic segmentation mask for a given image. In practice however, there is often considerable uncertainty about what constitutes the correct segmentation, and different expert annotators will often segment the same image differently. We tackle both of these problems with Tyche, a framework that uses a context set to generate stochastic predictions for previously unseen tasks without the need to retrain. Tyche differs from other in-context segmentation methods in two important ways. (1) We introduce a novel convolution block architecture that enables interactions among predictions. (2) We introduce in-context test-time augmentation, a new mechanism to provide prediction stochasticity. When combined with appropriate model design and loss functions, Tyche can predict a set of plausible diverse segmentation candidates for new or unseen medical images and segmentation tasks without the need to retrain. The Tyche code is available at: https://tyche.csail.mit.edu/

Hypernetworks, neural networks that predict the parameters of another neural network, are powerful models that have been successfully used in diverse applications from image generation to multi-task learning. Unfortunately, existing hypernetworks are often challenging to train. Training typically converges far more slowly than for non-hypernetwork models, and the rate of convergence can be very sensitive to hyperparameter choices. In this work, we identify a fundamental and previously unidentified problem that contributes to the challenge of training hypernetworks: a magnitude proportionality between the inputs and outputs of the hypernetwork. We demonstrate both analytically and empirically that this can lead to unstable optimization, thereby slowing down convergence, and sometimes even preventing any learning. We present a simple solution to this problem using a revised hypernetwork formulation that we call Magnitude Invariant Parametrizations (MIP). We demonstrate the proposed solution on several hypernetwork tasks, where it consistently stabilizes training and achieves faster convergence. Furthermore, we perform a comprehensive ablation study including choices of activation function, normalization strategies, input dimensionality, and hypernetwork architecture; and find that MIP improves training in all scenarios. We provide easy-to-use code that can turn existing networks into MIP-based hypernetworks.

Star-convex shapes arise across bio-microscopy and radiology in the form of nuclei, nodules, metastases, and other units. Existing instance segmentation networks for such structures train on densely labeled instances for each dataset, which requires substantial and often impractical manual annotation effort. Further, significant reengineering or finetuning is needed when presented with new datasets and imaging modalities due to changes in contrast, shape, orientation, resolution, and density. We present AnyStar, a domain-randomized generative model that simulates synthetic training data of blob-like objects with randomized appearance, environments, and imaging physics to train general-purpose star-convex instance segmentation networks. As a result, networks trained using our generative model do not require annotated images from un-seen datasets. A single network trained on our synthesized data accurately 3D segments C. elegans and P. dumerilii nuclei in fluorescence microscopy, mouse cortical nuclei in μCT, zebrafish brain nuclei in EM, and placental cotyledons in human fetal MRI, all without any retraining, finetuning, transfer learning, or domain adaptation. Code is available at https://github.com/neel-dey/AnyStar.

Neuroimage processing tasks like segmentation, reconstruction, and registration are central to the study of neuroscience. Robust deep learning strategies and architectures used to solve these tasks are often similar. Yet, when presented with a new task or a dataset with different visual characteristics, practitioners most often need to train a new model, or fine-tune an existing one. This is a time-consuming process that poses a substantial barrier for the thousands of neuroscientists and clinical researchers who often lack the resources or machine-learning expertise to train deep learning models. In practice, this leads to a lack of adoption of deep learning, and neuroscience tools being dominated by classical frameworks. We introduce Neuralizer, a single model that generalizes to previously unseen neuroimaging tasks and modalities without the need for retraining or fine-tuning. Tasks do not have to be known a priori, and generalization happens in a single forward pass during inference. The model can solve processing tasks across multiple image modalities, acquisition methods, and datasets, and generalize to tasks and modalities it has not been trained on. Our experiments on coronal slices show that when few annotated subjects are available, our multi-task network outperforms task-specific baselines without training on the task.

While deep learning models have become the predominant method for medical image segmentation, they are typically not capable of generalizing to unseen segmentation tasks involving new anatomies, image modalities, or labels. Given a new segmentation task, researchers generally have to train or fine-tune models. This is time-consuming and poses a substantial barrier for clinical researchers, who often lack the resources and expertise to train neural networks.We present UniverSeg, a method for solving unseen medical segmentation tasks without additional training. Given a query image and an example set of image-label pairs that define a new segmentation task, UniverSeg employs a new CrossBlock mechanism to produce accurate segmentation maps without additional training. To achieve generalization to new tasks, we have gathered and standardized a collection of 53 open-access medical segmentation datasets with over 22,000 scans, which we refer to as MegaMedical. We used this collection to train UniverSeg on a diverse set of anatomies and imaging modalities. We demonstrate that UniverSeg substantially outperforms several related methods on unseen tasks, and thoroughly analyze and draw insights about important aspects of the proposed system. The UniverSeg source code and model weights are freely available at https://universeg.csail.mit.edu

Convolutional Neural Networks (CNNs) are the predominant model used for a variety of medical image analysis tasks. At inference time, these models are computationally intensive, especially with volumetric data.In principle, it is possible to trade accuracy for computational efficiency by manipulating the rescaling factor in the downsample and upsample layers of CNN architectures.However, properly exploring the accuracy-efficiency trade-off is prohibitively expensive with existing models.To address this, we introduce Scale-Space HyperNetworks (SSHN), a method that learns a spectrum of CNNs with varying internal rescaling factors.A single SSHN characterizes an entire Pareto accuracy-efficiency curve of models that match, and occasionally surpass, the outcomes of training many separate networks with fixed rescaling factors.We demonstrate the proposed approach in several medical image analysis applications, comparing SSHN against strategies with both fixed and dynamic rescaling factors.We find that SSHN consistently provides a better accuracy-efficiency trade-off at a fraction of the training cost. Trained SSHNs enable the user to quickly choose a rescaling factor that appropriately balances accuracy and computational efficiency for their particular needs at inference.

Despite advances in data augmentation and transfer learning, convolutional neural networks (CNNs) difficultly generalise to unseen domains. When segmenting brain scans, CNNs are highly sensitive to changes in resolution and contrast: even within the same MRI modality, performance can decrease across datasets. Here we introduce SynthSeg, the first segmentation CNN robust against changes in contrast and resolution. SynthSeg is trained with synthetic data sampled from a generative model conditioned on segmentations. Crucially, we adopt a domain randomisation strategy where we fully randomise the contrast and resolution of the synthetic training data. Consequently, SynthSeg can segment real scans from a wide range of target domains without retraining or fine-tuning, which enables straightforward analysis of huge amounts of heterogeneous clinical data. Because SynthSeg only requires segmentations to be trained (no images), it can learn from labels obtained by automated methods on diverse populations (e.g., ageing and diseased), thus achieving robustness to a wide range of morphological variability. We demonstrate SynthSeg on 5,000 scans of six modalities (including CT) and ten resolutions, where it exhibits unparallelled generalisation compared with supervised CNNs, state-of-the-art domain adaptation, and Bayesian segmentation. Finally, we demonstrate the generalisability of SynthSeg by applying it to cardiac MRI and CT scans.

Image registration is a fundamental medical image analysis task, and a wide variety of approaches have been proposed. However, only a few studies have comprehensively compared medical image registration approaches on a wide range of clinically relevant tasks. This limits the development of registration methods, the adoption of research advances into practice, and a fair benchmark across competing approaches. The Learn2Reg challenge addresses these limitations by providing a multi-task medical image registration data set for comprehensive characterisation of deformable registration algorithms. A continuous evaluation will be possible at https://learn2reg.grand-challenge.org. Learn2Reg covers a wide range of anatomies (brain, abdomen, and thorax), modalities (ultrasound, CT, MR), availability of annotations, as well as intra- and inter-patient registration evaluation. We established an easily accessible framework for training and validation of 3D registration methods, which enabled the compilation of results of over 65 individual method submissions from more than 20 unique teams. We used a complementary set of metrics, including robustness, accuracy, plausibility, and runtime, enabling unique insight into the current state-of-the-art of medical image registration. This paper describes datasets, tasks, evaluation methods and results of the challenge, as well as results of further analysis of transferability to new datasets, the importance of label supervision, and resulting bias. While no single approach worked best across all tasks, many methodological aspects could be identified that push the performance of medical image registration to new state-of-the-art performance. Furthermore, we demystified the common belief that conventional registration methods have to be much slower than deep-learning-based methods.

The convolution operation is a central building block of neural network architectures widely used in computer vision. The size of the convolution kernels determines both the expressiveness of convolutional neural networks (CNN), as well as the number of learnable parameters. Increasing the network capacity to capture rich pixel relationships requires increasing the number of learnable parameters, often leading to overfitting and/or lack of robustness. In this paper, we propose a powerful novel building block, the hyper-convolution, which implicitly represents the convolution kernel as a function of kernel coordinates. Hyper-convolutions enable decoupling the kernel size, and hence its receptive field, from the number of learnable parameters. In our experiments, focused on challenging biomedical image segmentation tasks, we demonstrate that replacing regular convolutions with hyper-convolutions leads to more efficient architectures that achieve improved accuracy. Our analysis also shows that learned hyper-convolutions are naturally regularized, which can offer better generalization performance. We believe that hyper-convolutions can be a powerful building block in future neural network architectures for computer vision tasks. We provide all of our code here: https://github.com/tym002/Hyper-Convolution

We introduce a strategy for learning image registration without acquired imaging data, producing powerful networks agnostic to contrast introduced by magnetic resonance imaging (MRI). While classical registration methods accurately estimate the spatial correspondence between images, they solve an optimization problem for every new image pair. Learning-based techniques are fast at test time but limited to registering images with contrasts and geometric content similar to those seen during training. We propose to remove this dependency on training data by leveraging a generative strategy for diverse synthetic label maps and images that exposes networks to a wide range of variability, forcing them to learn more invariant features. This approach results in powerful networks that accurately generalize to a broad array of MRI contrasts. We present extensive experiments with a focus on 3D neuroimaging, showing that this strategy enables robust and accurate registration of arbitrary MRI contrasts even if the target contrast is not seen by the networks during training. We demonstrate registration accuracy surpassing the state of the art both within and across contrasts, using a single model. Critically, training on arbitrary shapes synthesized from noise distributions results in competitive performance, removing the dependency on acquired data of any kind. Additionally, since anatomical label maps are often available for the anatomy of interest, we show that synthesizing images from these dramatically boosts performance, while still avoiding the need for real intensity images. Our code is available at doic https://w3id.org/synthmorph.

Deformable templates are essential to large-scale medical image registration, segmentation, and population analysis. Current conventional and deep network-based methods for template construction use only regularized registration objectives and often yield templates with blurry and/or anatomically implausible appearance, confounding downstream biomedical interpretation. We reformulate deformable registration and conditional template estimation as an adversarial game wherein we encourage realism in the moved templates with a generative adversarial registration framework conditioned on flexible image covariates. The resulting templates exhibit significant gain in specificity to attributes such as age and disease, better fit underlying group-wise spatiotemporal trends, and achieve improved sharpness and centrality. These improvements enable more accurate population modeling with diverse covariates for standardized downstream analyses and easier anatomical delineation for structures of interest.

We introduce a new video synthesis task: synthesizing time lapse videos depicting how a given painting might have been created. Artists paint using unique combinations of brushes, strokes, and colors. There are often many possible ways to create a given painting. Our goal is to learn to capture this rich range of possibilities. Creating distributions of long-term videos is a challenge for learning-based video synthesis methods. We present a probabilistic model that, given a single image of a completed painting, recurrently synthesizes steps of the painting process. We implement this model as a convolutional neural network, and introduce a novel training scheme to enable learning from a limited dataset of painting time lapses. We demonstrate that this model can be used to sample many time steps, enabling long-term stochastic video synthesis. We evaluate our method on digital and watercolor paintings collected from video websites, and show that human raters find our synthetic videos to be similar to time lapse videos produced by real artists.

Optimized sensing is important for computational imaging in low-resource environments, when images must be recovered from severely limited measurements. In this paper, we propose a physics-constrained, fully differentiable, autoencoder that learns a probabilistic sensor-sampling strategy for optimized sensor design. The proposed method learns a system's preferred sampling distribution that characterizes the correlations between different sensor selections as a binary, fully-connected Ising model. The learned probabilistic model is achieved by using a Gibbs sampling inspired network architecture, and is trained end-to-end with a reconstruction network for efficient co-design. The proposed framework is applicable to sensor selection problems in a variety of computational imaging applications. In this paper, we demonstrate the approach in the context of a very-long-baseline-interferometry (VLBI) array design task, where sensor correlations and atmospheric noise present unique challenges. We demonstrate results broadly consistent with expectation, and draw attention to particular structures preferred in the telescope array geometry that can be leveraged to plan future observations and design array expansions.

Image segmentation is an important task in many medical applications. Methods based on convolutional neural networks attain state-of-the-art accuracy; however, they typically rely on supervised training with large labeled datasets. Labeling medical images requires significant expertise and time, and typical hand-tuned approaches for data augmentation fail to capture the complex variations in such images. We present an automated data augmentation method for synthesizing labeled medical images. We demonstrate our method on the task of segmenting magnetic resonance imaging (MRI) brain scans. Our method requires only a single segmented scan, and leverages other unlabeled scans in a semi-supervised approach. We learn a model of transformations from the images, and use the model along with the labeled example to synthesize additional labeled examples. Each transformation is comprised of a spatial deformation field and an intensity change, enabling the synthesis of complex effects such as variations in anatomy and image acquisition procedures. We show that training a supervised segmenter with these new examples provides significant improvements over state-of-the-art methods for one-shot biomedical image segmentation.

We introduce visual deprojection: the task of recovering an image or video that has been collapsed along a dimension. Projections arise in various contexts, such as long-exposure photography, where a dynamic scene is collapsed in time to produce a motion-blurred image, and corner cameras, where reflected light from a scene is collapsed along a spatial dimension because of an edge occluder to yield a 1D video. Deprojection is ill-posed-- often there are many plausible solutions for a given input. We first propose a probabilistic model capturing the ambiguity of the task. We then present a variational inference strategy using convolutional neural networks as functional approximators. Sampling from the inference network at test time yields plausible candidates from the distribution of original signals that are consistent with a given input projection. We evaluate the method on several datasets for both spatial and temporal deprojection tasks. We first demonstrate the method can recover human gait videos and face images from spatial projections, and then show that it can recover videos of moving digits from dramatically motion-blurred images obtained via temporal projection.

We develop a learning framework for building deformable templates, which play a fundamental role in many image analysis and computational anatomy tasks. Conventional methods for template creation and image alignment to the template have undergone decades of rich technical development. In these frameworks, templates are constructed using an iterative process of template estimation and alignment, which is often computationally very expensive. Due in part to this shortcoming, most methods compute a single template for the entire population of images, or a few templates for specific sub-groups of the data. In this work, we present a probabilistic model and efficient learning strategy that yields either universal or \textit{conditional} templates, jointly with a neural network that provides efficient alignment of the images to these templates. We demonstrate the usefulness of this method on a variety of domains, with a special focus on neuroimaging. This is particularly useful for clinical applications where a pre-existing template does not exist, or creating a new one with traditional methods can be prohibitively expensive. Our code and atlases are available online as part of the VoxelMorph library at http://voxelmorph.csail.mit.edu.

We present VoxelMorph, a fast learning-based framework for deformable, pairwise medical image registration. Traditional registration methods optimize an objective function for each pair of images, which can be time-consuming for large datasets or rich deformation models. In contrast to this approach, and building on recent learning-based methods, we formulate registration as a function that maps an input image pair to a deformation field that aligns these images. We parameterize the function via a convolutional neural network (CNN), and optimize the parameters of the neural network on a set of images. Given a new pair of scans, VoxelMorph rapidly computes a deformation field by directly evaluating the function. In this work, we explore two different training strategies. In the first (unsupervised) setting, we train the model to maximize standard image matching objective functions that are based on the image intensities. In the second setting, we leverage auxiliary segmentations available in the training data. We demonstrate that the unsupervised model's accuracy is comparable to state-of-the-art methods, while operating orders of magnitude faster. We also show that VoxelMorph trained with auxiliary data improves registration accuracy at test time, and evaluate the effect of training set size on registration. Our method promises to speed up medical image analysis and processing pipelines, while facilitating novel directions in learning-based registration and its applications. Our code is freely available at https://github.com/voxelmorph/voxelmorph.

We present an algorithm for creating high resolution anatomically plausible images consistent with acquired clinical brain MRI scans with large inter-slice spacing. Although large data sets of clinical images contain a wealth of information, time constraints during acquisition result in sparse scans that fail to capture much of the anatomy. These characteristics often render computational analysis impractical as many image analysis algorithms tend to fail when applied to such images. Highly specialized algorithms that explicitly handle sparse slice spacing do not generalize well across problem domains. In contrast, we aim to enable application of existing algorithms that were originally developed for high resolution research scans to significantly undersampled scans. We introduce a generative model that captures fine-scale anatomical structure across subjects in clinical image collections and derive an algorithm for filling in the missing data in scans with large inter-slice spacing. Our experimental results demonstrate that the resulting method outperforms state-of-the-art upsampling super-resolution techniques, and promises to facilitate subsequent analysis not previously possible with scans of this quality. Our implementation is freely available at https://github.com/adalca/papago.

We address the computational problem of novel human pose synthesis. Given an image of a person and a desired pose, we produce a depiction of that person in that pose, retaining the appearance of both the person and background. We present a modular generative neural network that synthesizes unseen poses using training pairs of images and poses taken from human action videos. Our network separates a scene into different body part and background layers, moves body parts to new locations and refines their appearances, and composites the new foreground with a hole-filled background. These subtasks, implemented with separate modules, are trained jointly using only a single target image as a supervised label. We use an adversarial discriminator to force our network to synthesize realistic details conditioned on pose. We demonstrate image synthesis results on three action classes: golf, yoga/workouts and tennis, and show that our method produces accurate results within action classes as well as across action classes. Given a sequence of desired poses, we also produce coherent videos of actions.

We present a fast learning-based algorithm for deformable, pairwise 3D medical image registration. Current registration methods optimize an objective function independently for each pair of images, which can be time-consuming for large data. We define registration as a parametric function, and optimize its parameters given a set of images from a collection of interest. Given a new pair of scans, we can quickly compute a registration field by directly evaluating the function using the learned parameters. We model this function using a CNN, and use a spatial transform layer to reconstruct one image from another while imposing smoothness constraints on the registration field. The proposed method does not require supervised information such as ground truth registration fields or anatomical landmarks. We demonstrate registration accuracy comparable to state-of-the-art 3D image registration, while operating orders of magnitude faster in practice. Our method promises to significantly speed up medical image analysis and processing pipelines, while facilitating novel directions in learning-based registration and its applications. Our code is available at https://github.com/balakg/voxelmorph.

We consider the problem of segmenting a biomedical image into anatomical regions of interest. We specifically address the frequent scenario where we have no paired training data that contains images and their manual segmentations. Instead, we employ unpaired segmentation images that we use to build an anatomical prior. Critically these segmentations can be derived from imaging data from a different dataset and imaging modality than the current task. We introduce a generative probabilistic model that employs the learned prior through a convolutional neural network to compute segmentations in an unsupervised setting. We conducted an empirical analysis of the proposed approach in the context of structural brain MRI segmentation, using a multi-study dataset of more than 14,000 scans. Our results show that an anatomical prior enables fast unsupervised segmentation which is typically not possible using standard convolutional networks. The integration of anatomical priors can facilitate CNN-based anatomical segmentation in a range of novel clinical problems, where few or no annotations are available and thus standard networks are not trainable. The code, model definitions and model weights are freely available at http://github.com/adalca/neuron.

Variational autoencoders (VAE) are a powerful and widely-used class of models to learn complex data distributions in an unsupervised fashion. One important limitation of VAEs is the prior assumption that latent sample representations are independent and identically distributed. However, for many important datasets, such as time-series of images, this assumption is too strong: accounting for covariances between samples, such as those in time, can yield to a more appropriate model specification and improve performance in downstream tasks. In this work, we introduce a new model, the Gaussian Process (GP) Prior Variational Autoencoder (GPPVAE), to specifically address this issue. The GPPVAE aims to combine the power of VAEs with the ability to model correlations afforded by GP priors. To achieve efficient inference in this new class of models, we leverage structure in the covariance matrix, and introduce a new stochastic backpropagation strategy that allows for computing stochastic gradients in a distributed and low-memory fashion. We show that our method outperforms conditional VAEs (CVAEs) and an adaptation of standard VAEs in two image data applications.

The advent of high-throughput sequencing (HTS) technologies is enabling sequencing of human genomes at a significantly lower cost. The availability of these genomes is hoped to enable novel medical diagnostics and treatment, specific to the individual, thus launching the era of personalized medicine. The data currently generated by HTS machines require extensive computational analysis in order to identify genomic variants present in the sequenced individual. In this paper, we overview HTS technologies and discuss several of the plethora of algorithms and tools designed to analyze HTS data, including algorithms for read mapping, as well as methods for identification of single-nucleotide polymorphisms, insertions/deletions and large-scale structural variants and copy-number variants from these mappings.

MOTIVATION: High-throughput sequencing (HTS) technologies are transforming the study of genomic variation. The various HTS technologies have different sequencing biases and error rates, and while most HTS technologies sequence the residues of the genome directly, generating base calls for each position, the Applied Biosystem's SOLiD platform generates dibase-coded (color space) sequences. While combining data from the various platforms should increase the accuracy of variation detection, to date there are only a few tools that can identify variants from color space data, and none that can analyze color space and regular (letter space) data together. RESULTS: We present VARiD--a probabilistic method for variation detection from both letter- and color-space reads simultaneously. VARiD is based on a hidden Markov model and uses the forward-backward algorithm to accurately identify heterozygous, homozygous and tri-allelic SNPs, as well as micro-indels. Our analysis shows that VARiD performs better than the AB SOLiD toolset at detecting variants from color-space data alone, and improves the calls dramatically when letter- and color-space reads are combined. AVAILABILITY: The toolset is freely available at http://compbio.cs.utoronto.ca/varid.

The development of Next Generation Sequencing technologies, capable of sequencing hundreds of millions of short reads (25-70 bp each) in a single run, is opening the door to population genomic studies of non-model species. In this paper we present SHRiMP - the SHort Read Mapping Package: a set of algorithms and methods to map short reads to a genome, even in the presence of a large amount of polymorphism. Our method is based upon a fast read mapping technique, separate thorough alignment methods for regular letter-space as well as AB SOLiD (color-space) reads, and a statistical model for false positive hits. We use SHRiMP to map reads from a newly sequenced Ciona savignyi individual to the reference genome. We demonstrate that SHRiMP can accurately map reads to this highly polymorphic genome, while confirming high heterozygosity of C. savignyi in this second individual. SHRiMP is freely available at http://compbio.cs.toronto.edu/shrimp.