Dataset Information

Unifying generative and discriminative learning principles.

ABSTRACT:

Background

The recognition of functional binding sites in genomic DNA remains one of the fundamental challenges of genome research. During the last decades, a plethora of different and well-adapted models has been developed, but only little attention has been payed to the development of different and similarly well-adapted learning principles. Only recently it was noticed that discriminative learning principles can be superior over generative ones in diverse bioinformatics applications, too.

Results

Here, we propose a generalization of generative and discriminative learning principles containing the maximum likelihood, maximum a posteriori, maximum conditional likelihood, maximum supervised posterior, generative-discriminative trade-off, and penalized generative-discriminative trade-off learning principles as special cases, and we illustrate its efficacy for the recognition of vertebrate transcription factor binding sites.

Conclusions

We find that the proposed learning principle helps to improve the recognition of transcription factor binding sites, enabling better computational approaches for extracting as much information as possible from valuable wet-lab data. We make all implementations available in the open-source library Jstacs so that this learning principle can be easily applied to other classification problems in the field of genome and epigenome analysis.

SUBMITTER: Keilwagen J

PROVIDER: S-EPMC2848239 | biostudies-literature | 2010 Feb

REPOSITORIES: biostudies-literature

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Publications

Unifying generative and discriminative learning principles.

Keilwagen Jens J Grau Jan J Posch Stefan S Strickert Marc M Grosse Ivo I

BMC bioinformatics 20100222

<h4>Background</h4>The recognition of functional binding sites in genomic DNA remains one of the fundamental challenges of genome research. During the last decades, a plethora of different and well-adapted models has been developed, but only little attention has been payed to the development of different and similarly well-adapted learning principles. Only recently it was noticed that discriminative learning principles can be superior over generative ones in diverse bioinformatics applications, ...[more]

PMID: 20175896

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Project description:A hybrid quantum-classical method for learning Boltzmann machines (BM) for a generative and discriminative task is presented. BM are undirected graphs with a network of visible and hidden nodes where the former is used as the reading site. In contrast, the latter is used to manipulate visible states' probability. In Generative BM, the samples of visible data imitate the probability distribution of a given data set. In contrast, the visible sites of discriminative BM are treated as Input/Output (I/O) reading sites where the conditional probability of output state is optimized for a given set of input states. The cost function for learning BM is defined as a weighted sum of Kullback-Leibler (KL) divergence and Negative conditional Log-likelihood (NCLL), adjusted using a hyper-parameter. Here, the KL Divergence is the cost for generative learning, and NCLL is the cost for discriminative learning. A Stochastic Newton-Raphson optimization scheme is presented. The gradients and the Hessians are approximated using direct samples of BM obtained through quantum annealing. Quantum annealers are hardware representing the physics of the Ising model that operates on low but finite temperatures. This temperature affects the probability distribution of the BM; however, its value is unknown. Previous efforts have focused on estimating this unknown temperature through regression of theoretical Boltzmann energies of sampled states with the probability of states sampled by the actual hardware. These approaches assume that the control parameter change does not affect the system temperature; however, this is usually untrue. Instead of using energies, the probability distribution of samples is employed to estimate the optimal parameter set, ensuring that the optimal set can be obtained from a single set of samples. The KL divergence and NCLL are optimized for the system temperature, and the result is used to rescale the control parameter set. The performance of this approach, as tested against the theoretically expected distributions, shows promising results for Boltzmann training on quantum annealers.

Project description:PurposeTo assess the contribution of a generative adversarial network (GAN) to improve intermanufacturer reproducibility of radiomic features (RFs).Materials and methodsThe authors retrospectively developed a cycle-GAN to translate texture information from chest radiographs acquired using one manufacturer (Siemens) to chest radiographs acquired using another (Philips), producing fake chest radiographs with different textures. The authors prospectively evaluated the ability of this texture-translation cycle-GAN to reduce the intermanufacturer variability of RFs extracted from the lung parenchyma. This study assessed the cycle-GAN's ability to fool several machine learning (ML) classifiers tasked with recognizing the manufacturer on the basis of chest radiography inputs. The authors also evaluated the cycle-GAN's ability to mislead radiologists who were asked to perform the same recognition task. Finally, the authors tested whether the cycle-GAN had an impact on radiomic diagnostic accuracy for chest radiography in patients with congestive heart failure (CHF).ResultsRFs, extracted from chest radiographs after the cycle-GAN's texture translation (fake chest radiographs), showed decreased intermanufacturer RF variability. Using cycle-GAN-generated chest radiographs as inputs, ML classifiers categorized the fake chest radiographs as belonging to the target manufacturer rather than to a native one. Moreover, cycle-GAN fooled two experienced radiologists who identified fake chest radiographs as belonging to a target manufacturer class. Finally, reducing intermanufacturer RF variability with cycle-GAN improved the discriminative power of RFs for patients without CHF versus patients with CHF (from 55% to 73.5%, P < .001).ConclusionBoth ML classifiers and radiologists had difficulty recognizing the chest radiographs' manufacturer. The cycle-GAN improved RF intermanufacturer reproducibility and discriminative power for identifying patients with CHF. This deep learning approach may help counteract the sensitivity of RFs to differences in acquisition.Supplemental material is available for this article.© RSNA, 2020See also the commentary by Alderson in this issue.

Dataset Information

Unifying generative and discriminative learning principles.

Background

Results

Conclusions

Publications

Unifying generative and discriminative learning principles.

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