MotivationAs RNA viruses mutate and adapt to environmental changes, often developing resistance to anti-viral vaccines and drugs, they form an ensemble of viral strains––a viral quasispecies. While high-throughput sequencing (HTS) has enabled in-depth studies of viral quasispecies, sequencing errors and limited read lengths render the problem of reconstructing the strains and estimating their spectrum challenging. Inference of viral quasispecies is difficult due to generally non-uniform frequencies of the strains, and is further exacerbated when the genetic distances between the strains are small.ResultsThis paper presents TenSQR, an algorithm that utilizes tensor factorization framework to analyze HTS data and reconstruct viral quasispecies characterized by highly uneven frequencies of its components. Fundamentally, TenSQR performs clustering with successive data removal to infer strains in a quasispecies in order from the most to the least abundant one; every time a strain is inferred, sequencing reads generated from that strain are removed from the dataset. The proposed successive strain reconstruction and data removal enables discovery of rare strains in a population and facilitates detection of deletions in such strains. Results on simulated datasets demonstrate that TenSQR can reconstruct full-length strains having widely different abundances, generally outperforming state-of-the-art methods at diversities 1–10% and detecting long deletions even in rare strains. A study on a real HIV-1 dataset demonstrates that TenSQR outperforms competing methods in experimental settings as well. Finally, we apply TenSQR to analyze a Zika virus sample and reconstruct the full-length strains it contains.Availability and implementationTenSQR is available at https://github.com/SoYeonA/TenSQR.Supplementary information Supplementary data are available at Bioinformatics online.

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Reconstructing components of a genomic mixture from data obtained by means of DNA sequencing is a challenging problem encountered in a variety of applications including single individual haplotyping and studies of viral communities. Highthroughput DNA sequencing platforms oversample mixture components to provide massive amounts of reads whose relative positions can be determined by mapping the reads to a known reference genome; assembly of the components, however, requires discovery of the reads' origin -an NP-hard problem that the existing methods struggle to solve with the required level of accuracy. In this paper, we present a learning framework based on a graph auto-encoder designed to exploit structural properties of sequencing data. The algorithm is a neural network which essentially trains to ignore sequencing errors and infers the posterior probabilities of the origin of sequencing reads. Mixture components are then reconstructed by finding consensus of the reads determined to originate from the same genomic component. Results on realistic synthetic as well as experimental data demonstrate that the proposed framework reliably assembles haplotypes and reconstructs viral communities, often significantly outperforming state-ofthe-art techniques.

Identifying modulation type of a received radio signal is a challenging problem encountered in many applications including radio interference mitigation and spectrum allocation. This problem is rendered challenging by the existence of a large number of modulation schemes and numerous sources of interference. Existing methods for monitoring spectrum readily collect large amounts of radio signals. However, existing state-of-the-art approaches to modulation classification struggle to reach desired levels of accuracy with computational efficiency practically feasible for implementation on low-cost computational platforms. To this end, we propose a learning framework based on an LSTM denoising autoencoder designed to extract robust and stable features from the noisy received signals, and detect the underlying modulation scheme. The method uses a compact architecture that may be implemented on low-cost computational devices while achieving or exceeding state-of-the-art classification accuracy. Experimental results on realistic synthetic and over-the-air radio data show that the proposed framework reliably and efficiently classifies radio signals, and often significantly outperform state-of-the-art approaches.

Haplotype assembly and viral quasispecies reconstruction are challenging tasks concerned with analysis of genomic mixtures using sequencing data. High-throughput sequencing technologies generate enormous amounts of short fragments (reads) which essentially oversample components of a mixture; the representation redundancy enables reconstruction of the components (haplotypes, viral strains). The reconstruction problem, known to be NP-hard, boils down to grouping together reads originating from the same component in a mixture. Existing methods struggle to solve this problem with required level of accuracy and low runtimes; the problem is becoming increasingly more challenging as the number and length of the components increase. This paper proposes a read clustering method based on a convolutional auto-encoder designed to first project sequenced fragments to a low-dimensional space and then estimate the probability of the read origin using learned embedded features. The components are reconstructed by finding consensus sequences that agglomerate reads from the same origin. Mini-batch stochastic gradient descent and dimension reduction of reads allow the proposed method to efficiently deal with massive numbers of long reads. Experiments on simulated, semi-experimental and experimental data demonstrate the ability of the proposed method to accurately reconstruct haplotypes and viral quasispecies, often demonstrating superior performance compared to state-of-the-art methods.