Search bioRxiv⌕ Search

bioRxiv · 10.1101/2022.05.04.490565

Identifying disease-associated circRNAs based on edge-weighted graph attention and heterogeneous graph neural network

Abstract

MotivationCircular RNAs (circRNAs) with varied biological activities are implicated in pathogenic processes, according to new findings. They are regarded as promising biomarkers for the diagnosis and prognosis due to their structural features. Computational approaches, as opposed to traditional experiments, can identify the circRNA-disease connections at a lower cost. Multi-source pathogenesis data can help to reduce data sparsity and infer probable connections at the system level. The majority of available approaches create a homologous network using multi-source data, but they lose the datas heterogeneity. Effective solutions that make use of the peculiarities of multi-source data are urgently needed. ResultsIn this paper, we propose a model (CDHGNN) based on edge-weighted graph attention and heterogeneous graph neural networks for discovering probable circRNA-disease correlations prediction. The circRNA network, miRNA network, disease network and heterogeneous network are constructed based on the introduced multi-source data on circRNAs, miRNAs, and diseases. The features for each type of node in the network are then extracted using a designed edge-weighted graph attention network model. Using the revised node features, we learn meta-path contextual information and use heterogeneous neural networks to assign attention weights to different types of edges. CDHGNN outperforms state-of-the-art algorithms with comparable accuracy, according to the findings of the trial. Edge-weighted graph attention networks and heterogeneous graph networks have both improved performance significantly. Furthermore, case studies suggest that CDHGNN is capable of identifying particular molecular connections and can be used to investigate pathogenic pathways. Contactjxwang@mail.csu.edu.cn

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Lu, C., Zhang, L., Zeng, M., Lan, W., Wang, J.. 2022-05-05. Identifying disease-associated circRNAs based on edge-weighted graph attention and heterogeneous graph neural network. https://doi.org/10.1101/2022.05.04.490565

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Algorithms for Designing Therapeutic Oligonucleotides on Pangenome Graphs

Designing therapeutic oligonucleotides that act reliably across human genetic diversity requires more than alignment to a single reference genome. Binding affinity of an siRNA or ASO to a usually complementary site in an mRNA target molecule is one main determinant of drug efficacy. Thus, variation in sub-populations can lead to failures in drug development if this variation reduces binding affinity. We provide a first methodological step towards principled, variant-aware design of therapeutic oligonucleotides. The genetic diversity in target genes, or specific regions thereof, is represented as a pangenome graph. We define individual or small sets of suitable therapeutic oligonucleotides by their ability to cover all paths in a directed acyclic graph within a bounded edit distance <= k. Edit distance is used as an accepted proxy to the commonly used binding affinity. We formalize the resulting computational problem and provide complexity results: NP-hardness of identifying such minimal sets even for k =0, and coNP-completeness of verifying the validity of a given set of oligonucleotides. Further, we propose algorithmic approaches operating on a product graph of an automaton (an Aho-Corasick DFA or an Ukkonen DFA) and the pangenome graph, as well as a dynamic programming-based lossless filter. We evaluate the approaches on gene-specific subgraphs of human pangenome graphs and demonstrate favorable performance compared to naive brute-force computation. Our results show that candidate target sites with a threshold of k <= 3 can be identified even for large, complex graphs where the brute-force computation did not complete within 24h. We observe that the dynamic programming-based lossless filter outperforms both product-graph approaches as well as brute-force baselines while maintaining an average approximation ratio < 1.5 across more than a hundred evaluated subgraphs. We also present examples where a small set of oligonucleotides constitutes a feasible solution where no single oligonucleotide with a threshold of k <= 2 covers all paths.

bioinformatics↗

Evolutionarily Conserved Fragments reveal modular architecture and expand functional coverage in bacteriophage proteins

Bacteriophage proteins evolve through extensive modular exchange, yet the sequence units underlying this process remain poorly defined. Classical domains are plausible evolutionary modules, but they incompletely annotate phage proteins and may not always coincide with the regions conserved across protein families. Here, we constructed 13,035 Evolutionarily Conserved Fragments (ECFs), grouped into 3,167 families, through large-scale HMM-HMM comparisons of proteins from 5,396 RefSeq phage genomes, without imposing predefined domain boundaries. ECFs overlapped substantially with ECOD and Pfam annotations but formed a heterogeneous spectrum comprising subdomains, domain-equivalent units, composite regions and fragments with no counterpart in either resource. Their relationships were frequently nested, indicating that conserved modules occur at multiple organisational scales. ECFs annotated 50% of phage representative proteins (at least doubling the coverage of either database), with the largest gains in structural and infection-related functions, a pattern replicated in independent metagenomic data. ECF families also showed function-dependent patterns of diversity and spatial segregation and provided functional associations for 23,925 protein families lacking detectable Pfam or ECOD domains. In receptor-binding proteins, ECFs subdivided established domains, delineated previously unannotated structural elements and recovered homologous regions where structural similarity was ambiguous. These results show that the evolutionary building blocks of phage proteins do not always coincide with classical domains, highlighting that evolutionary processes act across multiple scales. ECFs provide a complementary, sequence-derived framework for investigating how complex viral proteins are assembled, diversified and functionally organised.

bioinformatics↗

deepTools4: Faster, Scalable, and Modernized Genomic Data Analysis

The deepTools suite is widely used for quality control, summarization, and visualization of high-throughput sequencing data. However, as genomic datasets grow in scale and depth, existing tools often become computational bottlenecks. We present deepTools4, a modernized framework designed for high performance, scalability, and enhanced usability, while maintaining seamless integration with the Galaxy platform. Core functionality has been rewritten and thoroughly benchmarked, achieving substantial computational speed-ups. Visualization tools have been modernized to provide more intuitive, high-quality graphical outputs. In addition, our testing framework has been expanded to facilitate continuous development and ensure robustness. We demonstrate the utility of deepTools4 across diverse epigenomics and transcriptomics datasets, highlighting its ability to summarize genome-wide signals, apply a wide range of common normalization methods, and visualize enrichment patterns. The enhanced deepTools4 framework delivers a faster, more scalable solution for reproducible genome-wide analysis and interpretation across many sequencing modalities. Availability: https://github.com/deeptools/deepTools/

bioinformatics↗