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MyESL: A Software for Evolutionary Sparse Learning in Molecular Phylogenetics and Genomics.

Evolutionary sparse learning uses supervised machine learning to build evolutionary models where genomic sites loci are parameters. It uses the Least Absolute Shrinkage and Selection Operator with bi-level sparsity to connect a specific phylogenetic hypothesis with sequence variation across genomic loci. The MyESL software addresses the need for open-source tools to perform evolutionary sparse learning analyses, offering features to preprocess input phylogenomic alignments, post-process output models to generate molecular evolutionary metrics, and make Least Absolute Shrinkage and Selection Operator regression adaptable and efficient for phylogenetic trees and alignments. The core of MyESL, which constructs models with logistic regressions using bi-level sparsity, is written in C++. Its input data preprocessing and result post-processing tools are developed in Python. Compared to other tools, MyESL is more computationally efficient and provides evolution-friendly inputs and outputs. These features have already enabled the use of MyESL in two phylogenomic applications, one to identify outlier sequences and fragile clades in inferred phylogenies and another to build genetic models of convergent traits. In addition to the use in a Python environment, MyESL is available as a standalone executable compatible across multiple platforms, which can be directly integrated into scripts and third-party software. The source code, executable, and documentation for MyESL are openly accessible at https://github.com/kumarlabgit/MyESL.

Phylogeny↗

A variational method for learning sparse and overcomplete representations.

An expectation-maximization algorithm for learning sparse and overcomplete data representations is presented. The proposed algorithm exploits a variational approximation to a range of heavy-tailed distributions whose limit is the Laplacian. A rigorous lower bound on the sparse prior distribution is derived, which enables the analytic marginalization of a lower bound on the data likelihood. This lower bound enables the development of an expectation-maximization algorithm for learning the overcomplete basis vectors and inferring the most probable basis coefficients.

Journal Article↗

Bayesian learning of sparse gene regulatory networks.

Differential equations (DEs) have been the most widespread formalism for gene regulatory network (GRN) modeling, as they offer natural interpretation of biological processes, easy elucidation of gene relationships, and the capability of using efficient parameter estimation methods. However, an important limitation of DEs is their requirement of O(d(2)) parameters where d is the number of genes modeled, which often causes over-parameterization for large d, leading to the over-fitting of data and dense parameter sets that are hard to interpret. This paper presents the first effort to address the over-parameterization problem by applying the sparse Bayesian learning (SBL) method to sparsify the GRN model of DEs. SBL operates on the parsimony principle, with the objective to reduce the number of effective parameters by driving the redundant parameters to zero. The resulting sparse parameter set offers three important advantages for GRN inference: first, the inferred GRNs are more plausible, since the biological counterparts are known to be sparse; second, gene relationships can be more easily elucidated from sparse sets than from dense sets; and third, the solutions become more optimal and consistent, due to the reduction in the volume of solution space. Experiments are conducted on the yeast Saccharomyces cerevisiae time-series gene expression data, in which known regulatory events related to the cell cycle G1/S phase are reliably reproduced.

Bayes Theorem↗

Sparse multinomial logistic regression: fast algorithms and generalization bounds.

Recently developed methods for learning sparse classifiers are among the state-of-the-art in supervised learning. These methods learn classifiers that incorporate weighted sums of basis functions with sparsity-promoting priors encouraging the weight estimates to be either significantly large or exactly zero. From a learning-theoretic perspective, these methods control the capacity of the learned classifier by minimizing the number of basis functions used, resulting in better generalization. This paper presents three contributions related to learning sparse classifiers. First, we introduce a true multiclass formulation based on multinomial logistic regression. Second, by combining a bound optimization approach with a component-wise update procedure, we derive fast exact algorithms for learning sparse multiclass classifiers that scale favorably in both the number of training samples and the feature dimensionality, making them applicable even to large data sets in high-dimensional feature spaces. To the best of our knowledge, these are the first algorithms to perform exact multinomial logistic regression with a sparsity-promoting prior. Third, we show how nontrivial generalization bounds can be derived for our classifier in the binary case. Experimental results on standard benchmark data sets attest to the accuracy, sparsity, and efficiency of the proposed methods.

Algorithms↗

Constructing Bayesian formulations of sparse kernel learning methods.

We present here a simple technique that simplifies the construction of Bayesian treatments of a variety of sparse kernel learning algorithms. An incomplete Cholesky factorisation is employed to modify the dual parameter space, such that the Gaussian prior over the dual model parameters is whitened. The regularisation term then corresponds to the usual weight-decay regulariser, allowing the Bayesian analysis to proceed via the evidence framework of MacKay. There is in addition a useful by-product associated with the incomplete Cholesky factorisation algorithm, it also identifies a subset of the training data forming an approximate basis for the entire dataset in the kernel-induced feature space, resulting in a sparse model. Bayesian treatments of the kernel ridge regression (KRR) algorithm, with both constant and heteroscedastic (input dependent) variance structures, and kernel logistic regression (KLR) are provided as illustrative examples of the proposed method, which we hope will be more widely applicable.

Algorithms↗

APNet, an explainable sparse deep learning model to discover differentially active drivers of severe COVID-19.

MOTIVATION: Computational analyses of bulk and single-cell omics provide translational insights into complex diseases, such as COVID-19, by revealing molecules, cellular phenotypes, and signalling patterns that contribute to unfavourable clinical outcomes. Current in silico approaches dovetail differential abundance, biostatistics, and machine learning, but often overlook nonlinear proteomic dynamics, like post-translational modifications, and provide limited biological interpretability beyond feature ranking. RESULTS: We introduce APNet, a novel computational pipeline that combines differential activity analysis based on SJARACNe co-expression networks with PASNet, a biologically informed sparse deep learning model, to perform explainable predictions for COVID-19 severity. The APNet driver-pathway network ingests SJARACNe co-regulation and classification weights to aid result interpretation and hypothesis generation. APNet outperforms alternative models in patient classification across three COVID-19 proteomic datasets, identifying predictive drivers and pathways, including some confirmed in single-cell omics and highlighting under-explored biomarker circuitries in COVID-19. AVAILABILITY AND IMPLEMENTATION: APNet's R, Python scripts, and Cytoscape methodologies are available at https://github.com/BiodataAnalysisGroup/APNet.

COVID-19↗

Fast generalized cross-validation algorithm for sparse model learning.

We propose a fast, incremental algorithm for designing linear regression models. The proposed algorithm generates a sparse model by optimizing multiple smoothing parameters using the generalized cross-validation approach. The performances on synthetic and real-world data sets are compared with other incremental algorithms such as Tipping and Faul's fast relevance vector machine, Chen et al.'s orthogonal least squares, and Orr's regularized forward selection. The results demonstrate that the proposed algorithm is competitive.

Algorithms↗

Emergence of simple-cell receptive field properties by learning a sparse code for natural images.

The receptive fields of simple cells in mammalian primary visual cortex can be characterized as being spatially localized, oriented and bandpass (selective to structure at different spatial scales), comparable to the basis functions of wavelet transforms. One approach to understanding such response properties of visual neurons has been to consider their relationship to the statistical structure of natural images in terms of efficient coding. Along these lines, a number of studies have attempted to train unsupervised learning algorithms on natural images in the hope of developing receptive fields with similar properties, but none has succeeded in producing a full set that spans the image space and contains all three of the above properties. Here we investigate the proposal that a coding strategy that maximizes sparseness is sufficient to account for these properties. We show that a learning algorithm that attempts to find sparse linear codes for natural scenes will develop a complete family of localized, oriented, bandpass receptive fields, similar to those found in the primary visual cortex. The resulting sparse image code provides a more efficient representation for later stages of processing because it possesses a higher degree of statistical independence among its outputs.

Algorithms↗

Sparse Bayesian learning for efficient visual tracking.

This paper extends the use of statistical learning algorithms for object localization. It has been shown that object recognizers using kernel-SVMs can be elegantly adapted to localization by means of spatial perturbation of the SVM. While this SVM applies to each frame of a video independently of other frames, the benefits of temporal fusion of data are well-known. This is addressed here by using a fully probabilistic Relevance Vector Machine (RVM) to generate observations with Gaussian distributions that can be fused over time. Rather than adapting a recognizer, we build a displacement expert which directly estimates displacement from the target region. An object detector is used in tandem, for object verification, providing the capability for automatic initialization and recovery. This approach is demonstrated in real-time tracking systems where the sparsity of the RVM means that only a fraction of CPU time is required to track at frame rate. An experimental evaluation compares this approach to the state of the art showing it to be a viable method for long-term region tracking.

Algorithms↗

A simple Hebbian/anti-Hebbian network learns the sparse, independent components of natural images.

Slightly modified versions of an early Hebbian/anti-Hebbian neural network are shown to be capable of extracting the sparse, independent linear components of a prefiltered natural image set. An explanation for this capability in terms of a coupling between two hypothetical networks is presented. The simple networks presented here provide alternative, biologically plausible mechanisms for sparse, factorial coding in early primate vision.

Algorithms↗

Dictionary learning algorithms for sparse representation.

Algorithms for data-driven learning of domain-specific overcomplete dictionaries are developed to obtain maximum likelihood and maximum a posteriori dictionary estimates based on the use of Bayesian models with concave/Schur-concave (CSC) negative log priors. Such priors are appropriate for obtaining sparse representations of environmental signals within an appropriately chosen (environmentally matched) dictionary. The elements of the dictionary can be interpreted as concepts, features, or words capable of succinct expression of events encountered in the environment (the source of the measured signals). This is a generalization of vector quantization in that one is interested in a description involving a few dictionary entries (the proverbial "25 words or less"), but not necessarily as succinct as one entry. To learn an environmentally adapted dictionary capable of concise expression of signals generated by the environment, we develop algorithms that iterate between a representative set of sparse representations found by variants of FOCUSS and an update of the dictionary using these sparse representations. Experiments were performed using synthetic data and natural images. For complete dictionaries, we demonstrate that our algorithms have improved performance over other independent component analysis (ICA) methods, measured in terms of signal-to-noise ratios of separated sources. In the overcomplete case, we show that the true underlying dictionary and sparse sources can be accurately recovered. In tests with natural images, learned overcomplete dictionaries are shown to have higher coding efficiency than complete dictionaries; that is, images encoded with an overcomplete dictionary have both higher compression (fewer bits per pixel) and higher accuracy (lower mean square error).

Algorithms↗

A two-layer sparse coding model learns simple and complex cell receptive fields and topography from natural images.

The classical receptive fields of simple cells in the visual cortex have been shown to emerge from the statistical properties of natural images by forcing the cell responses to be maximally sparse, i.e. significantly activated only rarely. Here, we show that this single principle of sparseness can also lead to emergence of topography (columnar organization) and complex cell properties as well. These are obtained by maximizing the sparsenesses of locally pooled energies, which correspond to complex cell outputs. Thus, we obtain a highly parsimonious model of how these properties of the visual cortex are adapted to the characteristics of the natural input.

Humans↗

A multi-layer sparse coding network learns contour coding from natural images.

An important approach in visual neuroscience considers how the function of the early visual system relates to the statistics of its natural input. Previous studies have shown how many basic properties of the primary visual cortex, such as the receptive fields of simple and complex cells and the spatial organization (topography) of the cells, can be understood as efficient coding of natural images. Here we extend the framework by considering how the responses of complex cells could be sparsely represented by a higher-order neural layer. This leads to contour coding and end-stopped receptive fields. In addition, contour integration could be interpreted as top-down inference in the presented model.

Cerebral Cortex↗

Unsupervised learning of granule cell sparse codes enhances cerebellar adaptive control.

Marr [J. Physiol. (1969) 202, 437-470] and Albus [Math. Biosci. (1971) 10, 25-61] hypothesized that cerebellar learning is facilitated by a granule cell sparse code, i.e. a neural code in which the fraction of active neurons is low at any one time. In this paper, we re-examine this hypothesis in light of recent experimental and theoretical findings. We argue that cerebellar motor learning is enhanced by a sparse code that simultaneously maximizes information transfer between mossy fibers and granule cells, minimizes redundancies between granule cell discharges, and re-codes the mossy fiber inputs with an adaptive resolution such that inputs corresponding to large errors are finely encoded. We then propose that a set of biologically plausible unsupervised learning rules can produce such a code. To maintain a low mean firing rate compatible with a sparse code, an activity-dependent homeostatic mechanism sets the cells' thresholds. Then, to maximize information transfer, the mossy fiber--granule cell synapses are adjusted by a Hebbian rule. Furthermore, to minimize redundancies between granule cell discharges, the inhibitory Golgi cell--granule cell synapses are tuned by an anti-Hebbian rule. Finally, to allow adaptive resolution, a performance-based neuromodulator-like signal gates these three plastic processes. We integrate these gated learning rules into a simplified model of the cerebellum for arm movement control, and show that unsupervised learning of granule cell sparse codes greatly improves cerebellar adaptive motor control in comparison to a "fixed" Marr--Albus-type model. Until recently, activity-dependent cerebellar plasticity was thought to be largely confined to the granule cell--Purkinje cell synapses. This static view of the cerebellum is, however, quickly being replaced by an extremely dynamic view in which plasticity is omnipresent. The present theoretical study shows how several forms of plasticity in the granular layer of the cerebellum can produce fast, accurate and stable cerebellar learning.

Algorithms↗

Age of acquisition effects in adult lexical processing reflect loss of plasticity in maturing systems: insights from connectionist networks.

Early learned words are recognized and produced faster than later learned words. The authors showed that such age of acquisition effects are a natural property of connectionist models trained by back-propagation when patterns are introduced at different points into training and learning of early and late patterns is cumulative and interleaved. Analysis of hidden unit activations indicated that the age of acquisition effect reflects a gradual reduction in network plasticity and a consequent failure to differentiate late items as effectively as early ones. Further simulations examined the effects of vocabulary size, learning rate, sparseness of coding, use of a modified learning algorithm, loss of early items, acquisition of very late items, and lesioning the network. The relationship between age of acquisition and word frequency was explored, including analyses of how the relative influence of these factors is modulated by introducing weight decay.

Adult↗

Temporal sparseness of the premotor drive is important for rapid learning in a neural network model of birdsong.

Sparse neural codes have been widely observed in cortical sensory and motor areas. A striking example of sparse temporal coding is in the song-related premotor area high vocal center (HVC) of songbirds: The motor neurons innervating avian vocal muscles are driven by premotor nucleus robustus archistriatalis (RA), which is in turn driven by nucleus HVC. Recent experiments reveal that RA-projecting HVC neurons fire just one burst per song motif. However, the function of this remarkable temporal sparseness has remained unclear. Because birdsong is a clear example of a learned complex motor behavior, we explore in a neural network model with the help of numerical and analytical techniques the possible role of sparse premotor neural codes in song-related motor learning. In numerical simulations with nonlinear neurons, as HVC activity is made progressively less sparse, the minimum learning time increases significantly. Heuristically, this slowdown arises from increasing interference in the weight updates for different synapses. If activity in HVC is sparse, synaptic interference is reduced, and is minimized if each synapse from HVC to RA is used only once in the motif, which is the situation observed experimentally. Our numerical results are corroborated by a theoretical analysis of learning in linear networks, for which we derive a relationship between sparse activity, synaptic interference, and learning time. If songbirds acquire their songs under significant pressure to learn quickly, this study predicts that HVC activity, currently measured only in adults, should also be sparse during the sensorimotor phase in the juvenile bird. We discuss the relevance of these results, linking sparse codes and learning speed, to other multilayered sensory and motor systems.

Algorithms↗

Recruitment learning of boolean functions in sparse random networks.

This work presents a new class of neural network models constrained by biological levels of sparsity and weight-precision, and employing only local weight updates. Concept learning is accomplished through the rapid recruitment of existing network knowledge - complex knowledge being realised as a combination of existing basis concepts. Prior network knowledge is here obtained through the random generation of feedforward networks, with the resulting concept library tailored through distributional bias to suit a particular target class. Learning is exclusively local - through supervised Hebbian and Winnow updates - avoiding the necessity for backpropagation of error and allowing remarkably rapid learning. The approach is demonstrated upon concepts of varying difficulty, culminating in the well-known Monks and LED benchmark problems.

Algorithms↗

Image denoising via sparse and redundant representations over learned dictionaries.

We address the image denoising problem, where zero-mean white and homogeneous Gaussian additive noise is to be removed from a given image. The approach taken is based on sparse and redundant representations over trained dictionaries. Using the K-SVD algorithm, we obtain a dictionary that describes the image content effectively. Two training options are considered: using the corrupted image itself, or training on a corpus of high-quality image database. Since the K-SVD is limited in handling small image patches, we extend its deployment to arbitrary image sizes by defining a global image prior that forces sparsity over patches in every location in the image. We show how such Bayesian treatment leads to a simple and effective denoising algorithm. This leads to a state-of-the-art denoising performance, equivalent and sometimes surpassing recently published leading alternative denoising methods.

Algorithms↗