Dlugas, H. | Search bioRxiv

bioRxiv2026

Novel biologically relevant small RNA-sequencing alignment tool LevenMap for alignment to database of non-coding RNAs

A crucial aspect of the bioinformatics workflow in small RNA-sequencing is the alignment of reads to a database of reference ncRNAs. Alignment algorithms such as Bowtie, Burrows-Wheeler Aligner (BWA), and Spliced Transcripts Alignment to a Reference (STAR) - which are designed for aligning reads to a reference genome - are typically used. Aligning short RNA-sequenced reads to a database of non-coding RNAs (ncRNAs) is fundamentally a different task than aligning longer reads to a genome due to ncRNAs (i) having roughly the same number of nucleotides as the reads being aligned and (ii) being subsequences of other ncRNAs. To account for these differences, we developed the novel alignment algorithm LevenMap. Of all reads which exactly matched a reference ncRNA in a publicly available dataset, LevenMap aligned 100.0% of them to their respective ncRNA while all other aligners mapped less than 40% of these reads to their corresponding ncRNA. Furthermore, the mean ratio (length of read) / (length of corresponding reference ncRNA) of all aligned reads was 1.0 and 0.998 for LevenMap with at most zero and one mismatch(es) allowed, respectively; this ratio was no more than 0.51 for all other aligners. Overall, LevenMap is designed to account for the nuances of aligning small RNA-sequencing data to a database of reference ncRNAs and yields more biologically relevant counts compared to traditional aligners in this context. LevenMap is free and publicly available on GitHub: https://github.com/hdlugas/LevenMap.

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bioRxiv2022

Electrocardiogram feature extraction and interval measurements using optimal representative cycles from persistent homology

Cardiovascular diseases are among the leading causes of death, and their early detection and treatment is important for lowering their prevalence and mortality rate. Electrocardiograms (ECGs) record electrical activity of the heart to provide information used to diagnose and treat various cardiovascular diseases. Many approaches to computer-aided ECG analysis have been performed, including Fourier analysis, principal component analysis, analyzing morphological changes, and machine learning. Due to the high accuracy required of ECG-analysis software, there is no universally-agreed upon algorithm to identify P,Q,R,S, and T-waves and measure intervals of interest. Topological data analysis uses tools from algebraic topology to quantify hole-like shapes within data, and methods using persistence statistics and fractal dimension with machine learning have been applied to ECG signals in the context of detecting arrhythmias within recent years. To our knowledge, there does not exist a method of identifying P,Q,S, and T-waves and measuring intervals of interest which relies on topological features of the data, and we propose a novel topological method for performing these aspects of ECG analysis. Specifically, we establish criteria to identify cardinality-minimal and area-minimal 1-cycles with certain properties as P,Q,S, and T-waves. This yields a procedure for measuring the PR-interval, QT-interval, ST-segment, QRS-duration, P-wave duration, and T-wave duration in Lead II ECG data. We apply our procedure to 400 sets of simulated Lead II ECG signals and compare with the interval values set by the model. Additionally, the algorithm is used to identify cardinality-minimal and area-minimal 1-cycles as P,Q,S, and T-waves in two sets of 200 randomly sampled Lead II ECG signals of real patients with 11 common rhythms. Analysis of optimal 1-cycles identified as P,Q,S, and T-waves and comparison of interval measurements shows that 1-cycle reconstructions can provide useful information about the ECG signal and could hold utility in characterizing arrhythmias. Author summaryTopological data analysis (TDA) has been a rapidly growing field within the past 15 years and has found applications across many fields. In the context of TDA, several algorithms primarily using persistence barcode statistics and machine learning have been applied to electrocardiogram (ECG) signals in recent years. We use a topological data-analytic method to identify subsets of an ECG signal which are representative of certain topological features in the ECG signal, and we propose that those subsets coincide with the P,Q,S, and T-waves in the ECG signal. We then use information about these subsets of the signal identified as P,Q,S, and T-waves to measure the PR-interval, QT-interval, ST-segment, QRS-duration, P-wave duration, and T-wave duration. We demonstrate our method on both simulated and real Lead II ECG data. These results show how identifying subsets of an ECG signal with certain topological properties could be used in analyzing the morphology of the signal over time and in arrhythmia-detection algorithms.

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