ABSTRACT
The human reference genome is the most widely used resource in human genetics and is due for a major update. Its current structure is a linear composite of merged haplotypes from more than 20 people, with a single individual comprising most of the sequence. It contains biases and errors within a framework that does not represent global human genomic variation. A high-quality reference with global representation of common variants, including single-nucleotide variants, structural variants and functional elements, is needed. The Human Pangenome Reference Consortium aims to create a more sophisticated and complete human reference genome with a graph-based, telomere-to-telomere representation of global genomic diversity. Here we leverage innovations in technology, study design and global partnerships with the goal of constructing the highest-possible quality human pangenome reference. Our goal is to improve data representation and streamline analyses to enable routine assembly of complete diploid genomes. With attention to ethical frameworks, the human pangenome reference will contain a more accurate and diverse representation of global genomic variation, improve gene-disease association studies across populations, expand the scope of genomics research to the most repetitive and polymorphic regions of the genome, and serve as the ultimate genetic resource for future biomedical research and precision medicine.
Subject(s)
Genome, Human , Genomics , Genome, Human/genetics , Haplotypes/genetics , High-Throughput Nucleotide Sequencing , Humans , Sequence Analysis, DNAABSTRACT
The recent development and application of methods based on the general principle of "crosslinking and proximity ligation" (crosslink-ligation) are revolutionizing RNA structure studies in living cells. However, extracting structure information from such data presents unique challenges. Here, we introduce a set of computational tools for the systematic analysis of data from a wide variety of crosslink-ligation methods, specifically focusing on read mapping, alignment classification, and clustering. We design a new strategy to map short reads with irregular gaps at high sensitivity and specificity. Analysis of previously published data reveals distinct properties and bias caused by the crosslinking reactions. We perform rigorous and exhaustive classification of alignments and discover eight types of arrangements that provide distinct information on RNA structures and interactions. To deconvolve the dense and intertwined gapped alignments, we develop a network/graph-based tool Crosslinked RNA Secondary Structure Analysis using Network Techniques (CRSSANT), which enables clustering of gapped alignments and discovery of new alternative and dynamic conformations. We discover that multiple crosslinking and ligation events can occur on the same RNA, generating multisegment alignments to report complex high-level RNA structures and multi-RNA interactions. We find that alignments with overlapped segments are produced from potential homodimers and develop a new method for their de novo identification. Analysis of overlapping alignments revealed potential new homodimers in cellular noncoding RNAs and RNA virus genomes in the Picornaviridae family. Together, this suite of computational tools enables rapid and efficient analysis of RNA structure and interaction data in living cells.
Subject(s)
RNA, Untranslated , RNA , Algorithms , Cluster Analysis , RNA/chemistry , RNA/genetics , RNA, Untranslated/chemistry , Sequence Analysis, RNA/methods , SoftwareABSTRACT
K-mers are short DNA sequences that are used for genome sequence analysis. Applications that use k-mers include genome assembly and alignment. However, the wider bioinformatic use of these short sequences has challenges related to the massive scale of genomic sequence data. A single human genome assembly has billions of k-mers. As a result, the computational requirements for analyzing k-mer information is enormous, particularly when involving complete genome assemblies. To address these issues, we developed a new indexing data structure based on a hash table tuned for the lookup of short sequence keys. This web application, referred to as KmerKeys, provides performant, rapid query speeds for cloud computation on genome assemblies. We enable fuzzy as well as exact sequence searches of assemblies. To enable robust and speedy performance, the website implements cache-friendly hash tables, memory mapping and massive parallel processing. Our method employs a scalable and efficient data structure that can be used to jointly index and search a large collection of human genome assembly information. One can include variant databases and their associated metadata such as the gnomAD population variant catalogue. This feature enables the incorporation of future genomic information into sequencing analysis. KmerKeys is freely accessible at https://kmerkeys.dgi-stanford.org.
Subject(s)
Algorithms , Sequence Analysis, DNA , Software , Humans , Genome, Human , Genomics/methods , Sequence Analysis, DNA/methodsABSTRACT
MOTIVATION: Nanopore sequencing provides a real-time and portable solution to genomic sequencing, enabling better assembly, structural variant discovery and modified base detection than second generation technologies. The sequencing process generates a huge amount of data in the form of raw signal contained in fast5 files, which must be compressed to enable efficient storage and transfer. Since the raw data is inherently noisy, lossy compression has potential to significantly reduce space requirements without adversely impacting performance of downstream applications. RESULTS: We explore the use of lossy compression for nanopore raw data using two state-of-the-art lossy time-series compressors, and evaluate the tradeoff between compressed size and basecalling/consensus accuracy. We test several basecallers and consensus tools on a variety of datasets at varying depths of coverage, and conclude that lossy compression can provide 35-50% further reduction in compressed size of raw data over the state-of-the-art lossless compressor with negligible impact on basecalling accuracy (â²0.2% reduction) and consensus accuracy (â²0.002% reduction). In addition, we evaluate the impact of lossy compression on methylation calling accuracy and observe that this impact is minimal for similar reductions in compressed size, although further evaluation with improved benchmark datasets is required for reaching a definite conclusion. The results suggest the possibility of using lossy compression, potentially on the nanopore sequencing device itself, to achieve significant reductions in storage and transmission costs while preserving the accuracy of downstream applications. AVAILABILITYAND IMPLEMENTATION: The code is available at https://github.com/shubhamchandak94/lossy_compression_evaluation. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
ABSTRACT
MOTIVATION: High-Throughput Sequencing technologies produce huge amounts of data in the form of short genomic reads, associated quality values and read identifiers. Because of the significant structure present in these FASTQ datasets, general-purpose compressors are unable to completely exploit much of the inherent redundancy. Although there has been a lot of work on designing FASTQ compressors, most of them lack in support of one or more crucial properties, such as support for variable length reads, scalability to high coverage datasets, pairing-preserving compression and lossless compression. RESULTS: In this work, we propose SPRING, a reference-free compressor for FASTQ files. SPRING supports a wide variety of compression modes and features, including lossless compression, pairing-preserving compression, lossy compression of quality values, long read compression and random access. SPRING achieves substantially better compression than existing tools, for example, SPRING compresses 195 GB of 25× whole genome human FASTQ from Illumina's NovaSeq sequencer to less than 7 GB, around 1.6× smaller than previous state-of-the-art FASTQ compressors. SPRING achieves this improvement while using comparable computational resources. AVAILABILITY AND IMPLEMENTATION: SPRING can be downloaded from https://github.com/shubhamchandak94/SPRING. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Data Compression , High-Throughput Nucleotide Sequencing , Algorithms , Genome, Human , Genomics , Humans , Sequence Analysis, DNA , SoftwareABSTRACT
Recent advancements in sequencing technology have led to a drastic reduction in genome sequencing costs. This development has generated an unprecedented amount of data that must be stored, processed, and communicated. To facilitate this effort, compression of genomic files has been proposed. Specifically, lossy compression of quality scores is emerging as a natural candidate for reducing the growing costs of storage. A main goal of performing DNA sequencing in population studies and clinical settings is to identify genetic variation. Though the field agrees that smaller files are advantageous, the cost of lossy compression, in terms of variant discovery, is unclear.Bioinformatic algorithms to identify SNPs and INDELs use base quality score information; here, we evaluate the effect of lossy compression of quality scores on SNP and INDEL detection. Specifically, we investigate how the output of the variant caller when using the original data differs from that obtained when quality scores are replaced by those generated by a lossy compressor. Using gold standard genomic datasets and simulated data, we are able to analyze how accurate the output of the variant calling is, both for the original data and that previously lossily compressed. We show that lossy compression can significantly alleviate the storage while maintaining variant calling performance comparable to that with the original data. Further, in some cases lossy compression can lead to variant calling performance that is superior to that using the original file. We envisage our findings and framework serving as a benchmark in future development and analyses of lossy genomic data compressors.
Subject(s)
Databases, Genetic , Algorithms , Data Compression , Genome , Genomics , Humans , Sequence Analysis, DNAABSTRACT
Motivation: New Generation Sequencing (NGS) technologies for genome sequencing produce large amounts of short genomic reads per experiment, which are highly redundant and compressible. However, general-purpose compressors are unable to exploit this redundancy due to the special structure present in the data. Results: We present a new algorithm for compressing reads both with and without preserving the read order. In both cases, it achieves 1.4×-2× compression gain over state-of-the-art read compression tools for datasets containing as many as 3 billion Illumina reads. Our tool is based on the idea of approximately reordering the reads according to their position in the genome using hashed substring indices. We also present a systematic analysis of the read compression problem and compute bounds on fundamental limits of read compression. This analysis sheds light on the dynamics of the proposed algorithm (and read compression algorithms in general) and helps understand its performance in practice. The algorithm compresses only the read sequence, works with unaligned FASTQ files, and does not require a reference. Contact: schandak@stanford.edu. Supplementary information: Supplementary material are available at Bioinformatics online. The proposed algorithm is available for download at https://github.com/shubhamchandak94/HARC.
Subject(s)
Algorithms , Data Compression/methods , Genome , High-Throughput Nucleotide Sequencing/methods , Sequence Analysis, DNA/methods , Bacteria/genetics , Eukaryota/genetics , Genomics/methods , Humans , SoftwareABSTRACT
CONTRIBUTIONS: We developed a new lossless compression method for WIG data, named smallWig, offering the best known compression rates for RNA-seq data and featuring random access functionalities that enable visualization, summary statistics analysis and fast queries from the compressed files. Our approach results in order of magnitude improvements compared with bigWig and ensures compression rates only a fraction of those produced by cWig. The key features of the smallWig algorithm are statistical data analysis and a combination of source coding methods that ensure high flexibility and make the algorithm suitable for different applications. Furthermore, for general-purpose file compression, the compression rate of smallWig approaches the empirical entropy of the tested WIG data. For compression with random query features, smallWig uses a simple block-based compression scheme that introduces only a minor overhead in the compression rate. For archival or storage space-sensitive applications, the method relies on context mixing techniques that lead to further improvements of the compression rate. Implementations of smallWig can be executed in parallel on different sets of chromosomes using multiple processors, thereby enabling desirable scaling for future transcriptome Big Data platforms. MOTIVATION: The development of next-generation sequencing technologies has led to a dramatic decrease in the cost of DNA/RNA sequencing and expression profiling. RNA-seq has emerged as an important and inexpensive technology that provides information about whole transcriptomes of various species and organisms, as well as different organs and cellular communities. The vast volume of data generated by RNA-seq experiments has significantly increased data storage costs and communication bandwidth requirements. Current compression tools for RNA-seq data such as bigWig and cWig either use general-purpose compressors (gzip) or suboptimal compression schemes that leave significant room for improvement. To substantiate this claim, we performed a statistical analysis of expression data in different transform domains and developed accompanying entropy coding methods that bridge the gap between theoretical and practical WIG file compression rates. RESULTS: We tested different variants of the smallWig compression algorithm on a number of integer-and real- (floating point) valued RNA-seq WIG files generated by the ENCODE project. The results reveal that, on average, smallWig offers 18-fold compression rate improvements, up to 2.5-fold compression time improvements, and 1.5-fold decompression time improvements when compared with bigWig. On the tested files, the memory usage of the algorithm never exceeded 90 KB. When more elaborate context mixing compressors were used within smallWig, the obtained compression rates were as much as 23 times better than those of bigWig. For smallWig used in the random query mode, which also supports retrieval of the summary statistics, an overhead in the compression rate of roughly 3-17% was introduced depending on the chosen system parameters. An increase in encoding and decoding time of 30% and 55% represents an additional performance loss caused by enabling random data access. We also implemented smallWig using multi-processor programming. This parallelization feature decreases the encoding delay 2-3.4 times compared with that of a single-processor implementation, with the number of processors used ranging from 2 to 8; in the same parameter regime, the decoding delay decreased 2-5.2 times. AVAILABILITY AND IMPLEMENTATION: The smallWig software can be downloaded from: http://stanford.edu/~zhiyingw/smallWig/smallwig.html, http://publish.illinois.edu/milenkovic/, http://web.stanford.edu/~tsachy/. CONTACT: zhiyingw@stanford.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Algorithms , Data Compression/methods , High-Throughput Nucleotide Sequencing/methods , Sequence Analysis, RNA/methods , Humans , SoftwareABSTRACT
MOTIVATION: Data compression is crucial in effective handling of genomic data. Among several recently published algorithms, ERGC seems to be surprisingly good, easily beating all of the competitors. RESULTS: We evaluated ERGC and the previously proposed algorithms GDC and iDoComp, which are the ones used in the original paper for comparison, on a wide data set including 12 assemblies of human genome (instead of only four of them in the original paper). ERGC wins only when one of the genomes (referential or target) contains mixed-cased letters (which is the case for only the two Korean genomes). In all other cases ERGC is on average an order of magnitude worse than GDC and iDoComp. CONTACT: sebastian.deorowicz@polsl.pl, iochoa@stanford.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Data Compression , Sequence Analysis, DNA , Algorithms , Genome , Genome, Human , Genomics , HumansABSTRACT
MOTIVATION: The dramatic decrease in the cost of sequencing has resulted in the generation of huge amounts of genomic data, as evidenced by projects such as the UK10K and the Million Veteran Project, with the number of sequenced genomes ranging in the order of 10 K to 1 M. Due to the large redundancies among genomic sequences of individuals from the same species, most of the medical research deals with the variants in the sequences as compared with a reference sequence, rather than with the complete genomic sequences. Consequently, millions of genomes represented as variants are stored in databases. These databases are constantly updated and queried to extract information such as the common variants among individuals or groups of individuals. Previous algorithms for compression of this type of databases lack efficient random access capabilities, rendering querying the database for particular variants and/or individuals extremely inefficient, to the point where compression is often relinquished altogether. RESULTS: We present a new algorithm for this task, called GTRAC, that achieves significant compression ratios while allowing fast random access over the compressed database. For example, GTRAC is able to compress a Homo sapiens dataset containing 1092 samples in 1.1 GB (compression ratio of 160), while allowing for decompression of specific samples in less than a second and decompression of specific variants in 17 ms. GTRAC uses and adapts techniques from information theory, such as a specialized Lempel-Ziv compressor, and tailored succinct data structures. AVAILABILITY AND IMPLEMENTATION: The GTRAC algorithm is available for download at: https://github.com/kedartatwawadi/GTRAC CONTACT: : kedart@stanford.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Algorithms , Data Compression , Genomics , Sequence Analysis, DNA , Databases, Genetic , Genome , High-Throughput Nucleotide Sequencing , HumansABSTRACT
MOTIVATION: With the release of the latest next-generation sequencing (NGS) machine, the HiSeq X by Illumina, the cost of sequencing a Human has dropped to a mere $4000. Thus we are approaching a milestone in the sequencing history, known as the $1000 genome era, where the sequencing of individuals is affordable, opening the doors to effective personalized medicine. Massive generation of genomic data, including assembled genomes, is expected in the following years. There is crucial need for compression of genomes guaranteed of performing well simultaneously on different species, from simple bacteria to humans, which will ease their transmission, dissemination and analysis. Further, most of the new genomes to be compressed will correspond to individuals of a species from which a reference already exists on the database. Thus, it is natural to propose compression schemes that assume and exploit the availability of such references. RESULTS: We propose iDoComp, a compressor of assembled genomes presented in FASTA format that compresses an individual genome using a reference genome for both the compression and the decompression. In terms of compression efficiency, iDoComp outperforms previously proposed algorithms in most of the studied cases, with comparable or better running time. For example, we observe compression gains of up to 60% in several cases, including H.sapiens data, when comparing with the best compression performance among the previously proposed algorithms. AVAILABILITY: iDoComp is written in C and can be downloaded from: http://www.stanford.edu/~iochoa/iDoComp.html (We also provide a full explanation on how to run the program and an example with all the necessary files to run it.).
Subject(s)
Data Compression/methods , Databases, Factual , Genome, Human , Genomics/methods , High-Throughput Nucleotide Sequencing/methods , Sequence Analysis, DNA/methods , Software , Algorithms , Humans , Precision MedicineABSTRACT
MOTIVATION: Recent advancements in sequencing technology have led to a drastic reduction in the cost of sequencing a genome. This has generated an unprecedented amount of genomic data that must be stored, processed and transmitted. To facilitate this effort, we propose a new lossy compressor for the quality values presented in genomic data files (e.g. FASTQ and SAM files), which comprise roughly half of the storage space (in the uncompressed domain). Lossy compression allows for compression of data beyond its lossless limit. RESULTS: The proposed algorithm QVZ exhibits better rate-distortion performance than the previously proposed algorithms, for several distortion metrics and for the lossless case. Moreover, it allows the user to define any quasi-convex distortion function to be minimized, a feature not supported by the previous algorithms. Finally, we show that QVZ-compressed data exhibit better performance in the genotyping than data compressed with previously proposed algorithms, in the sense that for a similar rate, a genotyping closer to that achieved with the original quality values is obtained. AVAILABILITY AND IMPLEMENTATION: QVZ is written in C and can be downloaded from https://github.com/mikelhernaez/qvz. CONTACT: mhernaez@stanford.edu or gmalysa@stanford.edu or iochoa@stanford.edu SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.
Subject(s)
Algorithms , Data Compression/standards , Animals , Databases, Genetic , Genotype , Genotyping Techniques , Humans , Polymorphism, Single Nucleotide/geneticsABSTRACT
We begin by presenting a simple lossy compressor operating at near-zero rate: The encoder merely describes the indices of the few maximal source components, while the decoder's reconstruction is a natural estimate of the source components based on this information. This scheme turns out to be near optimal for the memoryless Gaussian source in the sense of achieving the zero-rate slope of its distortion-rate function. Motivated by this finding, we then propose a scheme comprised of iterating the above lossy compressor on an appropriately transformed version of the difference between the source and its reconstruction from the previous iteration. The proposed scheme achieves the rate distortion function of the Gaussian memoryless source (under squared error distortion) when employed on any finite-variance ergodic source. It further possesses desirable properties, and we, respectively, refer to as infinitesimal successive refinability, ratelessness, and complete separability. Its storage and computation requirements are of order no more than (n2)/(log ß n) per source symbol for ß > 0 at both the encoder and the decoder. Though the details of its derivation, construction, and analysis differ considerably, we discuss similarities between the proposed scheme and the recently introduced Sparse Regression Codes of Venkataramanan et al.
ABSTRACT
We study the problem of compression for the purpose of similarity identification, where similarity is measured by the mean square Euclidean distance between vectors. While the asymptotical fundamental limits of the problem - the minimal compression rate and the error exponent - were found in a previous work, in this paper we focus on the nonasymptotic domain and on practical, implementable schemes. We first present a finite blocklength achievability bound based on shape-gain quantization: The gain (amplitude) of the vector is compressed via scalar quantization and the shape (the projection on the unit sphere) is quantized using a spherical code. The results are numerically evaluated and they converge to the asymptotic values as predicted by the error exponent. We then give a nonasymptotic lower bound on the performance of any compression scheme, and compare to the upper (achievability) bound. For a practical implementation of such a scheme, we use wrapped spherical codes, studied by Hamkins and Zeger, and use the Leech lattice as an example for an underlying lattice. As a side result, we obtain a bound on the covering angle of any wrapped spherical code, as a function of the covering radius of the underlying lattice.
ABSTRACT
The problem of performing similarity queries on compressed data is considered. We focus on the quadratic similarity measure, and study the fundamental tradeoff between compression rate, sequence length, and reliability of queries performed on the compressed data. For a Gaussian source, we show that the queries can be answered reliably if and only if the compression rate exceeds a given threshold-the identification rate- which we explicitly characterize. Moreover, when compression is performed at a rate greater than the identification rate, responses to queries on the compressed data can be made exponentially reliable. We give a complete characterization of this exponent, which is analogous to the error and excess-distortion exponents in channel and source coding, respectively. For a general source, we prove that, as with classical compression, the Gaussian source requires the largest compression rate among sources with a given variance. Moreover, a robust scheme is described that attains this maximal rate for any source distribution.
ABSTRACT
We propose a general methodology for the construction and analysis of essentially minimax estimators for a wide class of functionals of finite dimensional parameters, and elaborate on the case of discrete distributions, where the support size S is unknown and may be comparable with or even much larger than the number of observations n. We treat the respective regions where the functional is nonsmooth and smooth separately. In the nonsmooth regime, we apply an unbiased estimator for the best polynomial approximation of the functional whereas, in the smooth regime, we apply a bias-corrected version of the maximum likelihood estimator (MLE). We illustrate the merit of this approach by thoroughly analyzing the performance of the resulting schemes for estimating two important information measures: 1) the entropy [Formula: see text] and 2) [Formula: see text], α > 0. We obtain the minimax L2 rates for estimating these functionals. In particular, we demonstrate that our estimator achieves the optimal sample complexity n â S/ln S for entropy estimation. We also demonstrate that the sample complexity for estimating Fα (P), 0 < α < 1, is n â S1/α /ln S, which can be achieved by our estimator but not the MLE. For 1 < α < 3/2, we show the minimax L2 rate for estimating Fα (P) is (n ln n)-2(α-1) for infinite support size, while the maximum L2 rate for the MLE is n-2(α-1). For all the above cases, the behavior of the minimax rate-optimal estimators with n samples is essentially that of the MLE (plug-in rule) with n ln n samples, which we term "effective sample size enlargement." We highlight the practical advantages of our schemes for the estimation of entropy and mutual information. We compare our performance with various existing approaches, and demonstrate that our approach reduces running time and boosts the accuracy. Moreover, we show that the minimax rate-optimal mutual information estimator yielded by our framework leads to significant performance boosts over the Chow-Liu algorithm in learning graphical models. The wide use of information measure estimation suggests that the insights and estimators obtained in this paper could be broadly applicable.
ABSTRACT
We study the problem of communicating a distributed correlated memoryless source over a memoryless network, from source nodes to destination nodes, under quadratic distortion constraints. We establish the following two complementary results: 1) for an arbitrary memoryless network, among all distributed memoryless sources of a given correlation, Gaussian sources are least compressible, that is, they admit the smallest set of achievable distortion tuples and 2) for any memoryless source to be communicated over a memoryless additive-noise network, among all noise processes of a given correlation, Gaussian noise admits the smallest achievable set of distortion tuples. We establish these results constructively by showing how schemes for the corresponding Gaussian problems can be applied to achieve similar performance for (source or noise) distributions that are not necessarily Gaussian but have the same covariance.
ABSTRACT
UNLABELLED: The number of human genomes that have been sequenced completely for different individuals has increased rapidly in recent years. Storing and transferring complete genomes between computers for the purpose of applying various applications and analysis tools will soon become a major hurdle, hindering the analysis phase. Therefore, there is a growing need to compress these data efficiently. Here, we describe a technique to compress human genomes based on entropy coding, using a reference genome and known Single Nucleotide Polymorphisms (SNPs). Furthermore, we explore several intrinsic features of genomes and information in other genomic databases to further improve the compression attained. Using these methods, we compress James Watson's genome to 2.5 megabytes (MB), improving on recent work by 37%. Similar compression is obtained for most genomes available from the 1000 Genomes Project. Our biologically inspired techniques promise even greater gains for genomes of lower organisms and for human genomes as more genomic data become available. AVAILABILITY: Code is available at sourceforge.net/projects/genomezip/
Subject(s)
Data Compression/methods , Genome, Human , Genomics/methods , Algorithms , Haplotypes , Humans , Polymorphism, Single NucleotideABSTRACT
BACKGROUND: Next Generation Sequencing technologies have revolutionized many fields in biology by reducing the time and cost required for sequencing. As a result, large amounts of sequencing data are being generated. A typical sequencing data file may occupy tens or even hundreds of gigabytes of disk space, prohibitively large for many users. This data consists of both the nucleotide sequences and per-base quality scores that indicate the level of confidence in the readout of these sequences. Quality scores account for about half of the required disk space in the commonly used FASTQ format (before compression), and therefore the compression of the quality scores can significantly reduce storage requirements and speed up analysis and transmission of sequencing data. RESULTS: In this paper, we present a new scheme for the lossy compression of the quality scores, to address the problem of storage. Our framework allows the user to specify the rate (bits per quality score) prior to compression, independent of the data to be compressed. Our algorithm can work at any rate, unlike other lossy compression algorithms. We envisage our algorithm as being part of a more general compression scheme that works with the entire FASTQ file. Numerical experiments show that we can achieve a better mean squared error (MSE) for small rates (bits per quality score) than other lossy compression schemes. For the organism PhiX, whose assembled genome is known and assumed to be correct, we show that it is possible to achieve a significant reduction in size with little compromise in performance on downstream applications (e.g., alignment). CONCLUSIONS: QualComp is an open source software package, written in C and freely available for download at https://sourceforge.net/projects/qualcomp.