Haohua Song, Wenhao Gu, Zhijing Li, Yunwenyu, Tiantian Zhu, Xiao Yang, Zexuan Zhu. Proceedings of the 64th Annual Meeting of the Association for Computational Linguistics (Volume 1: Long Papers). 2026.

MOTIVATION: The associations between biomarkers and human diseases play a key role in understanding complex pathology and developing targeted therapies. Wet lab experiments for biomarker discovery are costly, laborious and time-consuming. Computational prediction methods can be used to greatly expedite the identification of candidate biomarkers. RESULTS: Here, we present a novel computational model named GTGenie for predicting the biomarker-disease associations based on graph and text features. In GTGenie, a graph attention network is utilized to characterize diverse similarities of biomarkers and diseases from heterogeneous information resources. Meanwhile, a pretrained BERT-based model is applied to learn the text-based representation of biomarker-disease relation from biomedical literature. The captured graph and text features are then integrated in a bimodal fusion network to model the hybrid entity representation. Finally, inductive matrix completion is adopted to infer the missing entries for reconstructing relation matrix, with which the unknown biomarker-disease associations are predicted. Experimental results on HMDD, HMDAD and LncRNADisease data sets showed that GTGenie can obtain competitive prediction performance with other state-of-the-art methods. AVAILABILITY: The source code of GTGenie and the test data are available at: https://github.com/Wolverinerine/GTGenie.

The exponential growth of high-throughput DNA sequence data has posed great challenges to genomic data storage, retrieval and transmission. Compression is a critical tool to address these challenges, where many methods have been developed to reduce the storage size of the genomes and sequencing data (reads, quality scores and metadata). However, genomic data are being generated faster than they could be meaningfully analyzed, leaving a large scope for developing novel compression algorithms that could directly facilitate data analysis beyond data transfer and storage. In this article, we categorize and provide a comprehensive review of the existing compression methods specialized for genomic data and present experimental results on compression ratio, memory usage, time for compression and decompression. We further present the remaining challenges and potential directions for future research.

SUMMARY: Exhaustive mapping of next-generation sequencing data to a set of relevant reference sequences becomes an important task in pathogen discovery and metagenomic classification. However, the runtime and memory usage increase as the number of reference sequences and the repeat content among these sequences increase. In many applications, read mapping time dominates the entire application. We developed CompMap, a reference-based compression program, to speed up this process. CompMap enables the generation of a non-redundant representative sequence for the input sequences. We have demonstrated that reads can be mapped to this representative sequence with a much reduced time and memory usage, and the mapping to the original reference sequences can be recovered with high accuracy. AVAILABILITY AND IMPLEMENTATION: CompMap is implemented in C and freely available at http://csse.szu.edu.cn/staff/zhuzx/CompMap/. CONTACT: [email protected] SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

BACKGROUND: The exponential growth of next generation sequencing (NGS) data has posed big challenges to data storage, management and archive. Data compression is one of the effective solutions, where reference-based compression strategies can typically achieve superior compression ratios compared to the ones not relying on any reference. RESULTS: This paper presents a lossless light-weight reference-based compression algorithm namely LW-FQZip to compress FASTQ data. The three components of any given input, i.e., metadata, short reads and quality score strings, are first parsed into three data streams in which the redundancy information are identified and eliminated independently. Particularly, well-designed incremental and run-length-limited encoding schemes are utilized to compress the metadata and quality score streams, respectively. To handle the short reads, LW-FQZip uses a novel light-weight mapping model to fast map them against external reference sequence(s) and produce concise alignment results for storage. The three processed data streams are then packed together with some general purpose compression algorithms like LZMA. LW-FQZip was evaluated on eight real-world NGS data sets and achieved compression ratios in the range of 0.111-0.201. This is comparable or superior to other state-of-the-art lossless NGS data compression algorithms. CONCLUSIONS: LW-FQZip is a program that enables efficient lossless FASTQ data compression. It contributes to the state of art applications for NGS data storage and transmission. LW-FQZip is freely available online at: http://csse.szu.edu.cn/staff/zhuzx/LWFQZip.

UNLABELLED: Error Correction is important for most next-generation sequencing applications because highly accurate sequenced reads will likely lead to higher quality results. Many techniques for error correction of sequencing data from next-gen platforms have been developed in the recent years. However, compared with the fast development of sequencing technologies, there is a lack of standardized evaluation procedure for different error-correction methods, making it difficult to assess their relative merits and demerits. In this article, we provide a comprehensive review of many error-correction methods, and establish a common set of benchmark data and evaluation criteria to provide a comparative assessment. We present experimental results on quality, run-time, memory usage and scalability of several error-correction methods. Apart from providing explicit recommendations useful to practitioners, the review serves to identify the current state of the art and promising directions for future research. AVAILABILITY: All error-correction programs used in this article are downloaded from hosting websites. The evaluation tool kit is publicly available at: http://aluru-sun.ece.iastate.edu/doku.php?id=ecr.

Taxonomic clustering of species is an important and frequently arising problem in metagenomics. High-throughput next generation sequencing is facilitating the creation of large metagenomic samples, while at the same time making the clustering problem harder due to the short sequence length supported and unknown species sampled. In this paper, we present a parallel algorithm for hierarchical taxonomic clustering of large metagenomic samples with support for overlapping clusters. We adapt the sketching techniques originally developed for web document clustering to deduce significant similarities between pairs of sequences without resorting to expensive all vs. all alignments. We formulate the metagenomics classification problem as that of maximal quasi-clique enumeration in the resulting similarity graph, at multiple levels of the hierarchy as prescribed by different similarity thresholds. We cast execution of the underlying algorithmic steps as applications of the map-reduce framework to achieve a cloud based implementation. Apart from solving an important problem in metagenomics, this work demonstrates the applicability of map-reduce framework in relatively complicated algorithmic settings.

BACKGROUND: High-throughput short read sequencing is revolutionizing genomics and systems biology research by enabling cost-effective deep coverage sequencing of genomes and transcriptomes. Error detection and correction are crucial to many short read sequencing applications including de novo genome sequencing, genome resequencing, and digital gene expression analysis. Short read error detection is typically carried out by counting the observed frequencies of kmers in reads and validating those with frequencies exceeding a threshold. In case of genomes with high repeat content, an erroneous kmer may be frequently observed if it has few nucleotide differences with valid kmers with multiple occurrences in the genome. Error detection and correction were mostly applied to genomes with low repeat content and this remains a challenging problem for genomes with high repeat content. RESULTS: We develop a statistical model and a computational method for error detection and correction in the presence of genomic repeats. We propose a method to infer genomic frequencies of kmers from their observed frequencies by analyzing the misread relationships among observed kmers. We also propose a method to estimate the threshold useful for validating kmers whose estimated genomic frequency exceeds the threshold. We demonstrate that superior error detection is achieved using these methods. Furthermore, we break away from the common assumption of uniformly distributed errors within a read, and provide a framework to model position-dependent error occurrence frequencies common to many short read platforms. Lastly, we achieve better error correction in genomes with high repeat content. AVAILABILITY: The software is implemented in C++ and is freely available under GNU GPL3 license and Boost Software V1.0 license at "http://aluru-sun.ece.iastate.edu/doku.php?id = redeem". CONCLUSIONS: We introduce a statistical framework to model sequencing errors in next-generation reads, which led to promising results in detecting and correcting errors for genomes with high repeat content.

The advent of high-throughput short read technology is revolutionizing life sciences by providing an inexpensive way to sequence genomes at high coverage. Exploiting this technology requires the development of a de novo short read assembler, which is an important open problem that is garnering significant research effort. Current methods are largely limited to microbial organisms, whose genomes are two to three orders of magnitude smaller than complex mammalian and plant genomes. In this paper, we present the design and development of a parallel de novo short read assembler that can scale to large genomes with high coverage. Our approach is based on the string graph formulation. Input reads are mapped to short paths, and the genome is reconstructed as a superpath anchored by distance constraints inferred from read pairs. Our method can handle a mixture of multiple read sizes and multiple paired read distances. We present parallel algorithms for string graph construction, string graph compaction, graph based error detection and removal, and computing aggregate summarization of paired read links across graph edges. Using this, we navigate the final graph structure to reproduce large contiguous sequences from the underlying genome. We present a validation of our framework on experimental and simulated data from multiple known genomes and present scaling results on IBM Blue Gene/L.

MOTIVATION: Error correction is critical to the success of next-generation sequencing applications, such as resequencing and de novo genome sequencing. It is especially important for high-throughput short-read sequencing, where reads are much shorter and more abundant, and errors more frequent than in traditional Sanger sequencing. Processing massive numbers of short reads with existing error correction methods is both compute and memory intensive, yet the results are far from satisfactory when applied to real datasets. RESULTS: We present a novel approach, termed Reptile, for error correction in short-read data from next-generation sequencing. Reptile works with the spectrum of k-mers from the input reads, and corrects errors by simultaneously examining: (i) Hamming distance-based correction possibilities for potentially erroneous k-mers; and (ii) neighboring k-mers from the same read for correct contextual information. By not needing to store input data, Reptile has the favorable property that it can handle data that does not fit in main memory. In addition to sequence data, Reptile can make use of available quality score information. Our experiments show that Reptile outperforms previous methods in the percentage of errors removed from the data and the accuracy in true base assignment. In addition, a significant reduction in run time and memory usage have been achieved compared with previous methods, making it more practical for short-read error correction when sampling larger genomes. AVAILABILITY: Reptile is implemented in C++ and is available through the link: http://aluru-sun.ece.iastate.edu/doku.php?id=software CONTACT: [email protected].