Biology subjects

Eklund, A. C.

Publications and source records attributed to Eklund, A. C..

3 recordsLinked to original sources

bioRxiv2024

CHAMP delivers accurate taxonomic profiles of the prokaryotes, eukaryotes, and bacteriophages in the human microbiome

Accurate taxonomic profiling of the human microbiome composition is crucial for linking microbial species to health outcomes. Therefore, we created the Clinical Microbiomics Human Microbiome Profiler (CHAMP), a comprehensive tool designed for the profiling of prokaryotes, eukaryotes, and viruses across all body sites. Boasting a reference database derived from 30,382 human microbiome samples, CHAMP covers 6,567 prokaryotic and 244 eukaryotic species as well as 64,003 viruses. We used a diverse set of in silico metagenomes and DNA mock communities to benchmark CHAMP against the established profiling tools MetaPhlAn 4, Bracken 2, mOTUs 3, and Phanta. CHAMP demonstrated unparalleled species recall, F1 score, and significantly reduced false positives compared to all other tools benchmarked. Indeed, the false positive relative abundance (FPRA) for CHAMP was, on average, 50-fold lower than the second-best performing profiler. CHAMP also proved to be more robust than the other tools to low sequencing depths, highlighting its application for low biomass samples. Taken together, this establishes CHAMP as a best-in-class human microbiome profiler of prokaryotes, eukaryotes, and viruses in diverse and complex communities across low and high biomass samples. CHAMP profiling is offered as a service by Clinical Microbiomics A/S and available for a fee at https://cosmosidhub.com.

bioinformatics↗

bioRxiv2018

Strand Orientation Bias Detector (SOBDetector) to remove artifacts from sequencing data of formalin fixed samples

Formalin-fixed paraffin-embedded (FFPE) tissue, the most common tissue specimen stored in clinical practice, presents challenges in the analysis due to formalin-induced artifacts. Here we present SOBDetector, that is designed to remove these artifacts from a list of variants, which were extracted from next-generation sequencing data, using the posterior predictive distribution of a Bayesian logistic regression model trained on TCGA whole exomes. Based on a concordance analysis, SOBDetector outperforms the currently publicly available FFPE-filtration techniques (Accuracy: 0.9 {+/-} 0.015, AUC = 0.96). SOBDetector is implemented in Java 1.8 and is freely available online.

bioinformatics↗

bioRxiv2018

Breast cancer brain metastases show increased levels of genomic aberration based homologous recombination deficiency scores relative to their corresponding primary tumors

Due to its mechanism of action, PARP inhibitor therapy is expected to benefit mainly tumor cases with homologous recombination deficiency (HRD). Various measures of genomic scarring based HRD scores were developed as a companion diagnostic in order to correlate it with PARP inhibitor sensitivity. We compared a variety of HRD scores in primary tumors and their corresponding brain metastases and found a significant increase in this measure in brain metastases for all measures of HRD that were tested. This discrepancy warrants further investigation to assess whether this observation is common to other metastatic sites, and potentially a significant adjustment of strategy in the application of HRD measures in clinical trials for the prioritization of patients for PARP inhibitor therapy.\n\nKey messageWe quantified homologous recombination deficiency (HRD) in paired primary breast cancer and brain metastases samples based on a previously published data set. We showed that HRD significantly increases in the brain metastases relative to its paired primary tumor. An independent validation was also performed on another set of primary breast cancer and brain metastasis pairs using the \"my choice\" HRD score in collaboration with Myriad Genetics.\n\nThese confirmatory results suggest that brain metastases of breast cancer tend to have significantly higher HRD scores, which would prioritize those patients for PARP inhibitor therapy with those agents that cross the blood brain barrier such as veliparib and niraparib.

cancer biology↗