GSplit LBI: Taming the Procedural Bias in Neuroimaging for Disease Prediction

In voxel-based neuroimage analysis, lesion features have been the main focus in disease prediction due to their interpretability with respect to the related diseases. However, we observe that there exists another type of features introduced during the preprocessing steps and we call them "\textbf{Procedural Bias}". Besides, such bias can be leveraged to improve classification accuracy. Nevertheless, most existing models suffer from either under-fit without considering procedural bias or poor interpretability without differentiating such bias from lesion ones. In this paper, a novel dual-task algorithm namely \emph{GSplit LBI} is proposed to resolve this problem. By introducing an augmented variable enforced to be structural sparsity with a variable splitting term, the estimators for prediction and selecting lesion features can be optimized separately and mutually monitored by each other following an iterative scheme. Empirical experiments have been evaluated on the Alzheimer's Disease Neuroimaging Initiative\thinspace(ADNI) database. The advantage of proposed model is verified by improved stability of selected lesion features and better classification results.Comment: Conditional Accepted by Miccai,201

Modelling high-dimensional categorical data using nonconvex fusion penalties

We propose a method for estimation in high-dimensional linear models with nominal categorical data. Our estimator, called SCOPE, fuses levels together by making their corresponding coefficients exactly equal. This is achieved using the minimax concave penalty on differences between the order statistics of the coefficients for a categorical variable, thereby clustering the coefficients. We provide an algorithm for exact and efficient computation of the global minimum of the resulting nonconvex objective in the case with a single variable with potentially many levels, and use this within a block coordinate descent procedure in the multivariate case. We show that an oracle least squares solution that exploits the unknown level fusions is a limit point of the coordinate descent with high probability, provided the true levels have a certain minimum separation; these conditions are known to be minimal in the univariate case. We demonstrate the favourable performance of SCOPE across a range of real and simulated datasets. An R package CatReg implementing SCOPE for linear models and also a version for logistic regression is available on CRAN

Necessary and sufficient conditions of solution uniqueness in ℓ1\ell_1 minimization

This paper shows that the solutions to various convex $\ell_1$ minimization problems are \emph{unique} if and only if a common set of conditions are satisfied. This result applies broadly to the basis pursuit model, basis pursuit denoising model, Lasso model, as well as other $\ell_1$ models that either minimize $f(Ax-b)$ or impose the constraint $f(Ax-b)\leq\sigma$, where $f$ is a strictly convex function. For these models, this paper proves that, given a solution $x^*$ and defining I=\supp(x^*) and s=\sign(x^*_I), $x^*$ is the unique solution if and only if $A_I$ has full column rank and there exists $y$ such that $A_I^Ty=s$ and $|a_i^Ty|_\infty<1$ for $i\not\in I$. This condition is previously known to be sufficient for the basis pursuit model to have a unique solution supported on $I$. Indeed, it is also necessary, and applies to a variety of other $\ell_1$ models. The paper also discusses ways to recognize unique solutions and verify the uniqueness conditions numerically.Comment: 6 pages; revised version; submitte

Disease signatures are robust across tissues and experiments

Meta-analyses combining gene expression microarray experiments offer new insights into the molecular pathophysiology of disease not evident from individual experiments. Although the established technical reproducibility of microarrays serves as a basis for meta-analysis, pathophysiological reproducibility across experiments is not well established. In this study, we carried out a large-scale analysis of disease-associated experiments obtained from NCBI GEO, and evaluated their concordance across a broad range of diseases and tissue types. On evaluating 429 experiments, representing 238 diseases and 122 tissues from 8435 microarrays, we find evidence for a general, pathophysiological concordance between experiments measuring the same disease condition. Furthermore, we find that the molecular signature of disease across tissues is overall more prominent than the signature of tissue expression across diseases. The results offer new insight into the quality of public microarray data using pathophysiological metrics, and support new directions in meta-analysis that include characterization of the commonalities of disease irrespective of tissue, as well as the creation of multi-tissue systems models of disease pathology using public data

Deep Learning versus Classical Regression for Brain Tumor Patient Survival Prediction

Deep learning for regression tasks on medical imaging data has shown promising results. However, compared to other approaches, their power is strongly linked to the dataset size. In this study, we evaluate 3D-convolutional neural networks (CNNs) and classical regression methods with hand-crafted features for survival time regression of patients with high grade brain tumors. The tested CNNs for regression showed promising but unstable results. The best performing deep learning approach reached an accuracy of 51.5% on held-out samples of the training set. All tested deep learning experiments were outperformed by a Support Vector Classifier (SVC) using 30 radiomic features. The investigated features included intensity, shape, location and deep features. The submitted method to the BraTS 2018 survival prediction challenge is an ensemble of SVCs, which reached a cross-validated accuracy of 72.2% on the BraTS 2018 training set, 57.1% on the validation set, and 42.9% on the testing set. The results suggest that more training data is necessary for a stable performance of a CNN model for direct regression from magnetic resonance images, and that non-imaging clinical patient information is crucial along with imaging information.Comment: Contribution to The International Multimodal Brain Tumor Segmentation (BraTS) Challenge 2018, survival prediction tas

Differential expression analysis with global network adjustment

&lt;p&gt;Background: Large-scale chromosomal deletions or other non-specific perturbations of the transcriptome can alter the expression of hundreds or thousands of genes, and it is of biological interest to understand which genes are most profoundly affected. We present a method for predicting a gene’s expression as a function of other genes thereby accounting for the effect of transcriptional regulation that confounds the identification of genes differentially expressed relative to a regulatory network. The challenge in constructing such models is that the number of possible regulator transcripts within a global network is on the order of thousands, and the number of biological samples is typically on the order of 10. Nevertheless, there are large gene expression databases that can be used to construct networks that could be helpful in modeling transcriptional regulation in smaller experiments.&lt;/p&gt; &lt;p&gt;Results: We demonstrate a type of penalized regression model that can be estimated from large gene expression databases, and then applied to smaller experiments. The ridge parameter is selected by minimizing the cross-validation error of the predictions in the independent out-sample. This tends to increase the model stability and leads to a much greater degree of parameter shrinkage, but the resulting biased estimation is mitigated by a second round of regression. Nevertheless, the proposed computationally efficient “over-shrinkage” method outperforms previously used LASSO-based techniques. In two independent datasets, we find that the median proportion of explained variability in expression is approximately 25%, and this results in a substantial increase in the signal-to-noise ratio allowing more powerful inferences on differential gene expression leading to biologically intuitive findings. We also show that a large proportion of gene dependencies are conditional on the biological state, which would be impossible with standard differential expression methods.&lt;/p&gt; &lt;p&gt;Conclusions: By adjusting for the effects of the global network on individual genes, both the sensitivity and reliability of differential expression measures are greatly improved.&lt;/p&gt

A Comparison of Machine Learning Methods for Cross-Domain Few-Shot Learning

We present an empirical evaluation of machine learning algorithms in cross-domain few-shot learning based on a fixed pre-trained feature extractor. Experiments were performed in five target domains (CropDisease, EuroSAT, Food101, ISIC and ChestX) and using two feature extractors: a ResNet10 model trained on a subset of ImageNet known as miniImageNet and a ResNet152 model trained on the ILSVRC 2012 subset of ImageNet. Commonly used machine learning algorithms including logistic regression, support vector machines, random forests, nearest neighbour classification, naïve Bayes, and linear and quadratic discriminant analysis were evaluated on the extracted feature vectors. We also evaluated classification accuracy when subjecting the feature vectors to normalisation using p-norms. Algorithms originally developed for the classification of gene expression data—the nearest shrunken centroid algorithm and LDA ensembles obtained with random projections—were also included in the experiments, in addition to a cosine similarity classifier that has recently proved popular in few-shot learning. The results enable us to identify algorithms, normalisation methods and pre-trained feature extractors that perform well in cross-domain few-shot learning. We show that the cosine similarity classifier and ℓ² -regularised 1-vs-rest logistic regression are generally the best-performing algorithms. We also show that algorithms such as LDA yield consistently higher accuracy when applied to ℓ² -normalised feature vectors. In addition, all classifiers generally perform better when extracting feature vectors using the ResNet152 model instead of the ResNet10 model

Optimality Driven Nearest Centroid Classification from Genomic Data

Nearest-centroid classifiers have recently been successfully employed in high-dimensional applications, such as in genomics. A necessary step when building a classifier for high-dimensional data is feature selection. Feature selection is frequently carried out by computing univariate scores for each feature individually, without consideration for how a subset of features performs as a whole. We introduce a new feature selection approach for high-dimensional nearest centroid classifiers that instead is based on the theoretically optimal choice of a given number of features, which we determine directly here. This allows us to develop a new greedy algorithm to estimate this optimal nearest-centroid classifier with a given number of features. In addition, whereas the centroids are usually formed from maximum likelihood estimates, we investigate the applicability of high-dimensional shrinkage estimates of centroids. We apply the proposed method to clinical classification based on gene-expression microarrays, demonstrating that the proposed method can outperform existing nearest centroid classifiers

Representing complex data using localized principal components with application to astronomical data

Often the relation between the variables constituting a multivariate data space might be characterized by one or more of the terms: ``nonlinear'', ``branched'', ``disconnected'', ``bended'', ``curved'', ``heterogeneous'', or, more general, ``complex''. In these cases, simple principal component analysis (PCA) as a tool for dimension reduction can fail badly. Of the many alternative approaches proposed so far, local approximations of PCA are among the most promising. This paper will give a short review of localized versions of PCA, focusing on local principal curves and local partitioning algorithms. Furthermore we discuss projections other than the local principal components. When performing local dimension reduction for regression or classification problems it is important to focus not only on the manifold structure of the covariates, but also on the response variable(s). Local principal components only achieve the former, whereas localized regression approaches concentrate on the latter. Local projection directions derived from the partial least squares (PLS) algorithm offer an interesting trade-off between these two objectives. We apply these methods to several real data sets. In particular, we consider simulated astrophysical data from the future Galactic survey mission Gaia.Comment: 25 pages. In "Principal Manifolds for Data Visualization and Dimension Reduction", A. Gorban, B. Kegl, D. Wunsch, and A. Zinovyev (eds), Lecture Notes in Computational Science and Engineering, Springer, 2007, pp. 180--204, http://www.springer.com/dal/home/generic/search/results?SGWID=1-40109-22-173750210-

An effective non-parametric method for globally clustering genes from expression profiles

Clustering is widely used in bioinformatics to find gene correlation patterns. Although many algorithms have been proposed, these are usually confronted with difficulties in meeting the requirements of both automation and high quality. In this paper, we propose a novel algorithm for clustering genes from their expression profiles. The unique features of the proposed algorithm are twofold: it takes into consideration global, rather than local, gene correlation information in clustering processes; and it incorporates clustering quality measurement into the clustering processes to implement non-parametric, automatic and global optimal gene clustering. The evaluation on simulated and real gene data sets demonstrates the effectiveness of the algorithm. <br /