Neural-network-directed alignment of optical systems using the laser-beam spatial filter as an example

This report describes an effort at NASA Lewis Research Center to use artificial neural networks to automate the alignment and control of optical measurement systems. Specifically, it addresses the use of commercially available neural network software and hardware to direct alignments of the common laser-beam-smoothing spatial filter. The report presents a general approach for designing alignment records and combining these into training sets to teach optical alignment functions to neural networks and discusses the use of these training sets to train several types of neural networks. Neural network configurations used include the adaptive resonance network, the back-propagation-trained network, and the counter-propagation network. This work shows that neural networks can be used to produce robust sequencers. These sequencers can learn by example to execute the step-by-step procedures of optical alignment and also can learn adaptively to correct for environmentally induced misalignment. The long-range objective is to use neural networks to automate the alignment and operation of optical measurement systems in remote, harsh, or dangerous aerospace environments. This work also shows that when neural networks are trained by a human operator, training sets should be recorded, training should be executed, and testing should be done in a manner that does not depend on intellectual judgments of the human operator

Read alignment using deep neural networks

2019 Spring.Includes bibliographical references.Read alignment is the process of mapping short DNA sequences into the reference genome. With the advent of consecutively evolving "next generation" sequencing technologies, the need for sequence alignment tools appeared. Many scientific communities and the companies marketing the sequencing technologies developed a whole spectrum of read aligners/mappers for different error profiles and read length characteristics. Among the most recent successfully marketed sequencing technologies are Oxford Nanopore and PacBio SMRT sequencing, which are considered top players because of their extremely long reads and low cost. However, the reads may contain error up to 20% that are not generally uniformly distributed. To deal with that level of error rate and read length, proximity preserving hashing techniques, such as Minhash and Minimizers, were utilized to quickly map a read to the target region of the reference sequence. Subsequently, a variant of global or local alignment dynamic programming is then used to give the final alignment. In this research work, we train a Deep Neural Network (DNN) to yield a hashing scheme for the highly erroneous long reads, which is deemed superior to Minhash for mapping the reads. We implemented that idea to build a read alignment tool: DNNAligner. We evaluated the performance of our aligner against the popular read aligners in the bioinformatics community currently — minimap2, bwa-mem and graphmap. Our results show that the performance of DNNAligner is comparable to other tools without any code optimization or integration of other advanced features. Moreover, DNN exhibits superior performance in comparison with Minhashon neighborhood classification

Probabilistic methods for quality improvement in high-throughput sequencing data

Advances in high-throughput next-generation sequencing (NGS) technologies have enabled the determination of millions of nucleotide sequences in massive parallelism at affordable costs. Many studies have shown increased error rates over Sanger sequencing, in sequencing data produced by mainstream next-generation sequencing platforms, and have demonstrated the negative impacts of sequencing errors on a wide range of applications of NGS. Thus, it is critically important for primary analysis of sequencing data to produce accurate, high-quality nucleotides for downstream bioinformatics pipelines. Two bioinformatics problems are dedicated to the direct removal of sequencing errors: base-calling and error-correction. However, existing error correction methods are mostly algorithmic and heuristics. Few methods can address insertion and deletion errors, the dominant error type produced by many platforms. On the other hand, most base-callers do not model the underlying genome structures of the sequencing data, which are necessary for improving base-calling quality especially in low-quality regions. The sequential application of base-caller and error-corrector do not fully offset their shortcomings. In recognition of these issues, in this dissertation, we propose a probabilistic framework that closely emulate the sequencing-by-synthesis (SBS) process adopted by many NGS platforms. The core idea is to model sequencing data (individual reads, or fluorescent intensities) as independent emissions from a Hidden Markov model (HMM) with transition distributions to model local and double-stranded dependence in the genome, and emission distributions to model the subtle error characteristics of the sequencers. Deriving from this backbone, we develop three novel methods for improving the data quality of high-throughput sequencing: 1) PREMIER, an accurate probabilistic error corrector of substitution errors in Illumina data, 2) PREMIER-bc, an integrated base-caller and error corrector that significantly improves base-calling quality, and 3) PREMIER-indel, an extended error correction method that addresses substitution, insertion and deletion errors for SBS-based sequencers with good empirical performance. Our foray of using probabilistic methods for base-calling and error correction provides the immediate benefits to downstream analyses with increased sequencing data quality, and more importantly, a flexible and fully-probabilistic basis to go beyond primary analysis

Knowledge Driven Approaches and Machine Learning Improve the Identification of Clinically Relevant Somatic Mutations in Cancer Genomics

For cancer genomics to fully expand its utility from research discovery to clinical adoption, somatic variant detection pipelines must be optimized and standardized to ensure identification of clinically relevant mutations and to reduce laborious and error-prone post-processing steps. To address the need for improved catalogues of clinically and biologically important somatic mutations, we developed DoCM, a Database of Curated Mutations in Cancer (http://docm.info), as described in Chapter 2. DoCM is an open source, openly licensed resource to enable the cancer research community to aggregate, store and track biologically and clinically important cancer variants. DoCM is currently comprised of 1,364 variants in 132 genes across 122 cancer subtypes, based on the curation of 876 publications. To demonstrate the utility of this resource, the mutations in DoCM were used to identify variants of established significance in cancer that were missed by standard variant discovery pipelines (Chapter 3). Sequencing data from 1,833 cases across four TCGA projects were reanalyzed and 1,228 putative variants that were missed in the original TCGA reports were identified. Validation sequencing data were produced from 93 of these cases to confirm the putative variant we detected with DoCM. Here, we demonstrated that at least one functionally important variant in DoCM was recovered in 41% of cases studied. A major bottleneck in the DoCM analysis in Chapter 3 was the filtering and manual review of somatic variants. Several steps in this post-processing phase of somatic variant calling have already been automated. However, false positive filtering and manual review of variant candidates remains as a major challenge, especially in high-throughput discovery projects or in clinical cancer diagnostics. In Chapter 4, an approach that systematized and standardized the post-processing of somatic variant calls using machine learning algorithms, trained on 41,000 manually reviewed variants from 20 cancer genome projects, is outlined. The approach accurately reproduced the manual review process on hold out test samples, and accurately predicted which variants would be confirmed by orthogonal validation sequencing data. When compared to traditional manual review, this approach increased identification of clinically actionable variants by 6.2%. These chapters outline studies that result in substantial improvements in the identification and interpretation of somatic variants, the use of which can standardize and streamline cancer genomics, enabling its use at high throughput as well as clinically

Introducing deep learning -based methods into the variant calling analysis pipeline

Biological interpretation of the genetic variation enhances our understanding of normal and pathological phenotypes, and may lead to the development of new therapeutics. However, it is heavily dependent on the genomic data analysis, which might be inaccurate due to the various sequencing errors and inconsistencies caused by these errors. Modern analysis pipelines already utilize heuristic and statistical techniques, but the rate of falsely identified mutations remains high and variable, particular sequencing technology, settings and variant type. Recently, several tools based on deep neural networks have been published. The neural networks are supposed to find motifs in the data that were not previously seen. The performance of these novel tools is assessed in terms of precision and recall, as well as computational efficiency. Following the established best practices in both variant detection and benchmarking, the discussed tools demonstrate accuracy metrics and computational efficiency that spur further discussion

A pipeline for complete characterization of complex germline rearrangements from long DNA reads

横浜市立大学2021年

A step towards a reinforcement learning de novo genome assembler

The use of reinforcement learning has proven to be very promising for solving complex activities without human supervision during their learning process. However, their successful applications are predominantly focused on fictional and entertainment problems - such as games. Based on the above, this work aims to shed light on the application of reinforcement learning to solve this relevant real-world problem, the genome assembly. By expanding the only approach found in the literature that addresses this problem, we carefully explored the aspects of intelligent agent learning, performed by the Q-learning algorithm, to understand its suitability to be applied in scenarios whose characteristics are more similar to those faced by real genome projects. The improvements proposed here include changing the previously proposed reward system and including state space exploration optimization strategies based on dynamic pruning and mutual collaboration with evolutionary computing. These investigations were tried on 23 new environments with larger inputs than those used previously. All these environments are freely available on the internet for the evolution of this research by the scientific community. The results suggest consistent performance progress using the proposed improvements, however, they also demonstrate the limitations of them, especially related to the high dimensionality of state and action spaces. We also present, later, the paths that can be traced to tackle genome assembly efficiently in real scenarios considering recent, successfully reinforcement learning applications - including deep reinforcement learning - from other domains dealing with high-dimensional inputs

Bayesian Learning from Sequential Data using Gaussian Processes with Signature Covariances

We develop a Bayesian approach to learning from sequential data by using Gaussian processes (GPs) with so-called signature kernels as covariance functions. This allows to make sequences of different length comparable and to rely on strong theoretical results from stochastic analysis. Signatures capture sequential structure with tensors that can scale unfavourably in sequence length and state space dimension. To deal with this, we introduce a sparse variational approach with inducing tensors. We then combine the resulting GP with LSTMs and GRUs to build larger models that leverage the strengths of each of these approaches and benchmark the resulting GPs on multivariate time series (TS) classification datasets. Code available at https://github.com/tgcsaba/GPSig.Comment: Near camera ready version for ICML 2020. Previous title: "Variational Gaussian Processes with Signature Covariances

Deep Learning Techniques for Music Generation -- A Survey

This paper is a survey and an analysis of different ways of using deep learning (deep artificial neural networks) to generate musical content. We propose a methodology based on five dimensions for our analysis: Objective - What musical content is to be generated? Examples are: melody, polyphony, accompaniment or counterpoint. - For what destination and for what use? To be performed by a human(s) (in the case of a musical score), or by a machine (in the case of an audio file). Representation - What are the concepts to be manipulated? Examples are: waveform, spectrogram, note, chord, meter and beat. - What format is to be used? Examples are: MIDI, piano roll or text. - How will the representation be encoded? Examples are: scalar, one-hot or many-hot. Architecture - What type(s) of deep neural network is (are) to be used? Examples are: feedforward network, recurrent network, autoencoder or generative adversarial networks. Challenge - What are the limitations and open challenges? Examples are: variability, interactivity and creativity. Strategy - How do we model and control the process of generation? Examples are: single-step feedforward, iterative feedforward, sampling or input manipulation. For each dimension, we conduct a comparative analysis of various models and techniques and we propose some tentative multidimensional typology. This typology is bottom-up, based on the analysis of many existing deep-learning based systems for music generation selected from the relevant literature. These systems are described and are used to exemplify the various choices of objective, representation, architecture, challenge and strategy. The last section includes some discussion and some prospects.Comment: 209 pages. This paper is a simplified version of the book: J.-P. Briot, G. Hadjeres and F.-D. Pachet, Deep Learning Techniques for Music Generation, Computational Synthesis and Creative Systems, Springer, 201