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Dahlstrom, T. J.

Publications and source records attributed to Dahlstrom, T. J..

2 recordsLinked to original sources

mim: A lightweight auxiliary index to enable fast, parallel, gzipped FASTQ parsing

The FASTQ file format is the lingua franca of primary data distribution and processing across most of bioinformatics. Over time, the compression, storage, transmission, and decompression of gzip compressed fastq.gz files has become a substantial scalability bottleneck in the modern world of fast and massively parallel genomics tools and algorithms. In this work, we introduce mim: a lightweight, auxiliary index that enables fast, parallel, and highly-scalable parsing of compressed fastq.gz files. The creation of the mim index for a file is a one-time operation that can be performed in time comparable to that of simply decompressing and parsing the file (index creation induces [~] 20% overhead) and with minimal working memory. The mim index itself is very small, usually about [Formula]th of the size of the original compressed file, and can be easily stored along side the file or fetched from a remote location when it is needed. Further, the mim index is purely additive -- it does not modify the original gzipped FASTQ file in any way, nor require that the file be recompressed or rewritten -- and thus it does not require converting the massive back catalog of existing raw sequencing data. To demonstrate the feasibility and utility of the mim index, we benchmark construction of the mim index on a variety of existing gzipped FASTQ data, and also measure thread-scaling of mim index-assisted parallel FASTQ parsing on a simple parsing/ decompression-related task. We find that, for the one-time cost of index creation, and a small fraction of extra storage space, the mim index can massively accelerate the ingestion and parsing of gzipped FASTQ data, exhibiting near linear thread scaling in our experiments. mim is written in C++17, and is available as open source software under a BSD 3-clause license at https://github.com/COMBINE-lab/mim.

bioinformatics↗

Uncovering the Pathophysiological Pattern of Expression from Integrated Analysis across Uniformly Processed RNA Sequencing COVID-19 Datasets

BackgroundPost-acute sequelae of SARS-CoV-2 infection (PASC) affects millions globally, yet the molecular mechanisms underlying acute COVID-19 and its chronic sequelae remain poorly understood. MethodsWe performed an integrative transcriptomic analysis of three independent RNA-seq datasets, capturing the complete COVID-19 pathophysiology from health through acute severe infection to post-acute sequelae and mortality (n=142 total samples). We implemented a containerized analytical pipeline from data download, quantification, differential gene expression to uniformly process these three RNA-seq datasets. ResultsOur analysis reveals striking molecular dichotomies contrasting disease phases with profound clinical implications. Acute severe/critical COVID-19 reveals predominant enrichment of TNF- signaling via NF-{kappa}B pathways (normalized enrichment score >2.5, FDR <0.001), reflecting a cytokine storm pathophysiology characterized by rapid inflammatory developments involving IL-6, TNF-, and anti-apoptotic responses. In contrast, PASC patients exhibit dominant enrichment of Myc Targets V1 and Oxidative Phosphorylation pathways (NES >2.2, FDR <0.005), indicating important shifts toward cellular adaptation. Pathway signature analysis identifies core differentially expressed genes that reliably distinguish disease phases, thereby offering objective biomarkers for precision diagnosis and monitoring. ConclusionsThese findings establish a comprehensive molecular framework distinguishing acute inflammatory from chronic metabolic COVID-19 phases, with potential clinical applicability. TNF-/NF-{kappa}B pathway signatures identify patients at risk for severe disease progression, while Myc/OXPHOS signatures allow objective PASC diagnosis, addressing current reliance on subjective and eliminative diagnosis. This integrative analytical framework has utility beyond COVID-19, offering an applicable approach for precision medicine implementation across other diseases processes. Clinical SignificanceThis study transforms COVID-19 from a symptom-based to a molecularly-defined disease spectrum, enabling precision diagnosis, prognostic monitoring, classification, and targeted therapeutic possibilities based on pathway-specific biomarkers rather than subjective clinical assessments.

genomics↗