arXiv subjects

Christoph Lippert

Publications and source records attributed to Christoph Lippert.

At least 37 records · Page 2Linked to original sources

arXiv2023

DCID: Deep Canonical Information Decomposition

We consider the problem of identifying the signal shared between two one-dimensional target variables, in the presence of additional multivariate observations. Canonical Correlation Analysis (CCA)-based methods have traditionally been used to identify shared variables, however, they were designed for multivariate targets and only offer trivial solutions for univariate cases. In the context of Multi-Task Learning (MTL), various models were postulated to learn features that are sparse and shared across multiple tasks. However, these methods were typically evaluated by their predictive performance. To the best of our knowledge, no prior studies systematically evaluated models in terms of correctly recovering the shared signal. Here, we formalize the setting of univariate shared information retrieval, and propose ICM, an evaluation metric which can be used in the presence of ground-truth labels, quantifying 3 aspects of the learned shared features. We further propose Deep Canonical Information Decomposition (DCID) - a simple, yet effective approach for learning the shared variables. We benchmark the models on a range of scenarios on synthetic data with known ground-truths and observe DCID outperforming the baselines in a wide range of settings. Finally, we demonstrate a real-life application of DCID on brain Magnetic Resonance Imaging (MRI) data, where we are able to extract more accurate predictors of changes in brain regions and obesity. The code for our experiments as well as the supplementary materials are available at https://github.com/alexrakowski/dcid

cs.LG↗

arXiv2023

Training Normalizing Flows from Dependent Data

Normalizing flows are powerful non-parametric statistical models that function as a hybrid between density estimators and generative models. Current learning algorithms for normalizing flows assume that data points are sampled independently, an assumption that is frequently violated in practice, which may lead to erroneous density estimation and data generation. We propose a likelihood objective of normalizing flows incorporating dependencies between the data points, for which we derive a flexible and efficient learning algorithm suitable for different dependency structures. We show that respecting dependencies between observations can improve empirical results on both synthetic and real-world data, and leads to higher statistical power in a downstream application to genome-wide association studies.

cs.LG↗

arXiv2023

Iterative Patch Selection for High-Resolution Image Recognition

High-resolution images are prevalent in various applications, such as autonomous driving and computer-aided diagnosis. However, training neural networks on such images is computationally challenging and easily leads to out-of-memory errors even on modern GPUs. We propose a simple method, Iterative Patch Selection (IPS), which decouples the memory usage from the input size and thus enables the processing of arbitrarily large images under tight hardware constraints. IPS achieves this by selecting only the most salient patches, which are then aggregated into a global representation for image recognition. For both patch selection and aggregation, a cross-attention based transformer is introduced, which exhibits a close connection to Multiple Instance Learning. Our method demonstrates strong performance and has wide applicability across different domains, training regimes and image sizes while using minimal accelerator memory. For example, we are able to finetune our model on whole-slide images consisting of up to 250k patches (>16 gigapixels) with only 5 GB of GPU VRAM at a batch size of 16.

cs.CV↗

arXiv2022

Less Is More: A Comparison of Active Learning Strategies for 3D Medical Image Segmentation

Since labeling medical image data is a costly and labor-intensive process, active learning has gained much popularity in the medical image segmentation domain in recent years. A variety of active learning strategies have been proposed in the literature, but their effectiveness is highly dependent on the dataset and training scenario. To facilitate the comparison of existing strategies and provide a baseline for evaluating novel strategies, we evaluate the performance of several well-known active learning strategies on three datasets from the Medical Segmentation Decathlon. Additionally, we consider a strided sampling strategy specifically tailored to 3D image data. We demonstrate that both random and strided sampling act as strong baselines and discuss the advantages and disadvantages of the studied methods. To allow other researchers to compare their work to our results, we provide an open-source framework for benchmarking active learning strategies on a variety of medical segmentation datasets.

cs.CV↗

arXiv2021

ContIG: Self-supervised Multimodal Contrastive Learning for Medical Imaging with Genetics

High annotation costs are a substantial bottleneck in applying modern deep learning architectures to clinically relevant medical use cases, substantiating the need for novel algorithms to learn from unlabeled data. In this work, we propose ContIG, a self-supervised method that can learn from large datasets of unlabeled medical images and genetic data. Our approach aligns images and several genetic modalities in the feature space using a contrastive loss. We design our method to integrate multiple modalities of each individual person in the same model end-to-end, even when the available modalities vary across individuals. Our procedure outperforms state-of-the-art self-supervised methods on all evaluated downstream benchmark tasks. We also adapt gradient-based explainability algorithms to better understand the learned cross-modal associations between the images and genetic modalities. Finally, we perform genome-wide association studies on the features learned by our models, uncovering interesting relationships between images and genetic data.

cs.CV↗

arXiv2021

Self-Supervised Learning for 3D Medical Image Analysis using 3D SimCLR and Monte Carlo Dropout

Self-supervised learning methods can be used to learn meaningful representations from unlabeled data that can be transferred to supervised downstream tasks to reduce the need for labeled data. In this paper, we propose a 3D self-supervised method that is based on the contrastive (SimCLR) method. Additionally, we show that employing Bayesian neural networks (with Monte-Carlo Dropout) during the inference phase can further enhance the results on the downstream tasks. We showcase our models on two medical imaging segmentation tasks: i) Brain Tumor Segmentation from 3D MRI, ii) Pancreas Tumor Segmentation from 3D CT. Our experimental results demonstrate the benefits of our proposed methods in both downstream data-efficiency and performance.

cs.LG↗

arXiv2021

Explainability Requires Interactivity

When explaining the decisions of deep neural networks, simple stories are tempting but dangerous. Especially in computer vision, the most popular explanation approaches give a false sense of comprehension to its users and provide an overly simplistic picture. We introduce an interactive framework to understand the highly complex decision boundaries of modern vision models. It allows the user to exhaustively inspect, probe, and test a network's decisions. Across a range of case studies, we compare the power of our interactive approach to static explanation methods, showing how these can lead a user astray, with potentially severe consequences.

cs.LG↗

arXiv2020

3D Self-Supervised Methods for Medical Imaging

Self-supervised learning methods have witnessed a recent surge of interest after proving successful in multiple application fields. In this work, we leverage these techniques, and we propose 3D versions for five different self-supervised methods, in the form of proxy tasks. Our methods facilitate neural network feature learning from unlabeled 3D images, aiming to reduce the required cost for expert annotation. The developed algorithms are 3D Contrastive Predictive Coding, 3D Rotation prediction, 3D Jigsaw puzzles, Relative 3D patch location, and 3D Exemplar networks. Our experiments show that pretraining models with our 3D tasks yields more powerful semantic representations, and enables solving downstream tasks more accurately and efficiently, compared to training the models from scratch and to pretraining them on 2D slices. We demonstrate the effectiveness of our methods on three downstream tasks from the medical imaging domain: i) Brain Tumor Segmentation from 3D MRI, ii) Pancreas Tumor Segmentation from 3D CT, and iii) Diabetic Retinopathy Detection from 2D Fundus images. In each task, we assess the gains in data-efficiency, performance, and speed of convergence. Interestingly, we also find gains when transferring the learned representations, by our methods, from a large unlabeled 3D corpus to a small downstream-specific dataset. We achieve results competitive to state-of-the-art solutions at a fraction of the computational expense. We publish our implementations for the developed algorithms (both 3D and 2D versions) as an open-source library, in an effort to allow other researchers to apply and extend our methods on their datasets.

cs.CV↗

arXiv2020

Multimodal Self-Supervised Learning for Medical Image Analysis

Self-supervised learning approaches leverage unlabeled samples to acquire generic knowledge about different concepts, hence allowing for annotation-efficient downstream task learning. In this paper, we propose a novel self-supervised method that leverages multiple imaging modalities. We introduce the multimodal puzzle task, which facilitates rich representation learning from multiple image modalities. The learned representations allow for subsequent fine-tuning on different downstream tasks. To achieve that, we learn a modality-agnostic feature embedding by confusing image modalities at the data-level. Together with the Sinkhorn operator, with which we formulate the puzzle solving optimization as permutation matrix inference instead of classification, they allow for efficient solving of multimodal puzzles with varying levels of complexity. In addition, we also propose to utilize cross-modal generation techniques for multimodal data augmentation used for training self-supervised tasks. In other words, we exploit synthetic images for self-supervised pretraining, instead of downstream tasks directly, in order to circumvent quality issues associated with synthetic images, while improving data-efficiency and representations quality. Our experimental results, which assess the gains in downstream performance and data-efficiency, show that solving our multimodal puzzles yields better semantic representations, compared to treating each modality independently. Our results also highlight the benefits of exploiting synthetic images for self-supervised pretraining. We showcase our approach on four downstream tasks: Brain tumor segmentation and survival days prediction using four MRI modalities, Prostate segmentation using two MRI modalities, and Liver segmentation using unregistered CT and MRI modalities. We outperform many previous solutions, and achieve results competitive to state-of-the-art.

cs.CV↗

arXiv2020

Beyond the Mean-Field: Structured Deep Gaussian Processes Improve the Predictive Uncertainties

Deep Gaussian Processes learn probabilistic data representations for supervised learning by cascading multiple Gaussian Processes. While this model family promises flexible predictive distributions, exact inference is not tractable. Approximate inference techniques trade off the ability to closely resemble the posterior distribution against speed of convergence and computational efficiency. We propose a novel Gaussian variational family that allows for retaining covariances between latent processes while achieving fast convergence by marginalising out all global latent variables. After providing a proof of how this marginalisation can be done for general covariances, we restrict them to the ones we empirically found to be most important in order to also achieve computational efficiency. We provide an efficient implementation of our new approach and apply it to several benchmark datasets. It yields excellent results and strikes a better balance between accuracy and calibrated uncertainty estimates than its state-of-the-art alternatives.

stat.ML↗

arXiv2020

Two-sample Testing Using Deep Learning

We propose a two-sample testing procedure based on learned deep neural network representations. To this end, we define two test statistics that perform an asymptotic location test on data samples mapped onto a hidden layer. The tests are consistent and asymptotically control the type-1 error rate. Their test statistics can be evaluated in linear time (in the sample size). Suitable data representations are obtained in a data-driven way, by solving a supervised or unsupervised transfer-learning task on an auxiliary (potentially distinct) data set. If no auxiliary data is available, we split the data into two chunks: one for learning representations and one for computing the test statistic. In experiments on audio samples, natural images and three-dimensional neuroimaging data our tests yield significant decreases in type-2 error rate (up to 35 percentage points) compared to state-of-the-art two-sample tests such as kernel-methods and classifier two-sample tests.

stat.ML↗

arXiv2019

Integrating omics and MRI data with kernel-based tests and CNNs to identify rare genetic markers for Alzheimer's disease

For precision medicine and personalized treatment, we need to identify predictive markers of disease. We focus on Alzheimer's disease (AD), where magnetic resonance imaging scans provide information about the disease status. By combining imaging with genome sequencing, we aim at identifying rare genetic markers associated with quantitative traits predicted from convolutional neural networks (CNNs), which traditionally have been derived manually by experts. Kernel-based tests are a powerful tool for associating sets of genetic variants, but how to optimally model rare genetic variants is still an open research question. We propose a generalized set of kernels that incorporate prior information from various annotations and multi-omics data. In the analysis of data from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we evaluate whether (i) CNNs yield precise and reliable brain traits, and (ii) the novel kernel-based tests can help to identify loci associated with AD. The results indicate that CNNs provide a fast, scalable and precise tool to derive quantitative AD traits and that new kernels integrating domain knowledge can yield higher power in association tests of very rare variants.

stat.ML↗

arXiv2017

Sparse Probit Linear Mixed Model

Linear Mixed Models (LMMs) are important tools in statistical genetics. When used for feature selection, they allow to find a sparse set of genetic traits that best predict a continuous phenotype of interest, while simultaneously correcting for various confounding factors such as age, ethnicity and population structure. Formulated as models for linear regression, LMMs have been restricted to continuous phenotypes. We introduce the Sparse Probit Linear Mixed Model (Probit-LMM), where we generalize the LMM modeling paradigm to binary phenotypes. As a technical challenge, the model no longer possesses a closed-form likelihood function. In this paper, we present a scalable approximate inference algorithm that lets us fit the model to high-dimensional data sets. We show on three real-world examples from different domains that in the setup of binary labels, our algorithm leads to better prediction accuracies and also selects features which show less correlation with the confounding factors.

stat.ML↗

arXiv2016

Accurate Liability Estimation Improves Power in Ascertained Case Control Studies

Linear mixed models (LMMs) have emerged as the method of choice for confounded genome-wide association studies. However, the performance of LMMs in non-randomly ascertained case-control studies deteriorates with increasing sample size. We propose a framework called LEAP (Liability Estimator As a Phenotype, https://github.com/omerwe/LEAP) that tests for association with estimated latent values corresponding to severity of phenotype, and demonstrate that this can lead to a substantial power increase.

q-bio.GN↗

arXiv2014

Genetic Analysis of Transformed Phenotypes

Linear mixed models (LMMs) are a powerful and established tool for studying genotype-phenotype relationships. A limiting assumption of LMMs is that the residuals are Gaussian distributed, a requirement that rarely holds in practice. Violations of this assumption can lead to false conclusions and losses in power, and hence it is common practice to pre-process the phenotypic values to make them Gaussian, for instance by applying logarithmic or other non-linear transformations. Unfortunately, different phenotypes require different specific transformations, and choosing a "good" transformation is in general challenging and subjective. Here, we present an extension of the LMM that estimates an optimal transformation from the observed data. In extensive simulations and applications to real data from human, mouse and yeast we show that using such optimal transformations lead to increased power in genome-wide association studies and higher accuracy in heritability estimates and phenotype predictions.

q-bio.GN↗

arXiv2013

A powerful and efficient set test for genetic markers that handles confounders

Approaches for testing sets of variants, such as a set of rare or common variants within a gene or pathway, for association with complex traits are important. In particular, set tests allow for aggregation of weak signal within a set, can capture interplay among variants, and reduce the burden of multiple hypothesis testing. Until now, these approaches did not address confounding by family relatedness and population structure, a problem that is becoming more important as larger data sets are used to increase power. Results: We introduce a new approach for set tests that handles confounders. Our model is based on the linear mixed model and uses two random effects-one to capture the set association signal and one to capture confounders. We also introduce a computational speedup for two-random-effects models that makes this approach feasible even for extremely large cohorts. Using this model with both the likelihood ratio test and score test, we find that the former yields more power while controlling type I error. Application of our approach to richly structured GAW14 data demonstrates that our method successfully corrects for population structure and family relatedness, while application of our method to a 15,000 individual Crohn's disease case-control cohort demonstrates that it additionally recovers genes not recoverable by univariate analysis. Availability: A Python-based library implementing our approach is available at http://mscompbio.codeplex.com

q-bio.GN↗

arXiv2012

easyGWAS: An integrated interspecies platform for performing genome-wide association studies

Motivation: The rapid growth in genome-wide association studies (GWAS) in plants and animals has brought about the need for a central resource that facilitates i) performing GWAS, ii) accessing data and results of other GWAS, and iii) enabling all users regardless of their background to exploit the latest statistical techniques without having to manage complex software and computing resources. Results: We present easyGWAS, a web platform that provides methods, tools and dynamic visualizations to perform and analyze GWAS. In addition, easyGWAS makes it simple to reproduce results of others, validate findings, and access larger sample sizes through merging of public datasets. Availability: Detailed method and data descriptions as well as tutorials are available in the supplementary materials. easyGWAS is available at http://easygwas.tuebingen.mpg.de/. Contact: dominik.grimm@tuebingen.mpg.de

q-bio.GN↗

arXiv2012

A mixed model approach for joint genetic analysis of alternatively spliced transcript isoforms using RNA-Seq data

RNA-Seq technology allows for studying the transcriptional state of the cell at an unprecedented level of detail. Beyond quantification of whole-gene expression, it is now possible to disentangle the abundance of individual alternatively spliced transcript isoforms of a gene. A central question is to understand the regulatory processes that lead to differences in relative abundance variation due to external and genetic factors. Here, we present a mixed model approach that allows for (i) joint analysis and genetic mapping of multiple transcript isoforms and (ii) mapping of isoform-specific effects. Central to our approach is to comprehensively model the causes of variation and correlation between transcript isoforms, including the genomic background and technical quantification uncertainty. As a result, our method allows to accurately test for shared as well as transcript-specific genetic regulation of transcript isoforms and achieves substantially improved calibration of these statistical tests. Experiments on genotype and RNA-Seq data from 126 human HapMap individuals demonstrate that our model can help to obtain a more fine-grained picture of the genetic basis of gene expression variation.

q-bio.GN↗