Biology subjects

Höjer, P.

Publications and source records attributed to Höjer, P..

3 recordsLinked to original sources

bioRxiv2025

Comparative analysis of whole genome amplification kits for single cell genome analysis

Whole genome amplification (WGA) enables detailed analysis of genomic heterogeneity at the cellular level. Here, we systematically compare two commercially available WGA technologies on single cells; Multiple Displacement Amplification in the Qiagen REPLI-g kit (MDA/REPLI-g) and Primary Template-directed Amplification in the BioSkryb ResolveDNA kit (PTA/ResolveDNA). Beyond quality control and genomic profiling, we assessed a cost-effective array-based approach as a complement to low-pass sequencing. Consistent with available benchmarks, PTA/ResolveDNA sequencing libraries consistently outperformed MDA/REPLI-g across quality metrics, including genome coverage breadth and uniformity. CNV calls from PTA-cells showed higher accuracy and sensitivity, including reliable detection of small CNVs at low sequencing depth. SNP array-based analysis corroborated sequencing-based findings, and additionally provided allelic information. Notably, CNV detection from SNP arrays matched the performance of low-pass sequencing, supporting its utility as an cost-effective approach for WGA quality control and single-cell CNV profiling.

genomics↗

bioRxiv2025

Whole genome sequencing with AVITI and NovaSeq X Plus reveals comparable performance with contextual biases

Element Biosciences avidity sequencing has emerged as a competing technology to Illuminas short read sequencing platform. Prior benchmarks of avidity sequencing have not included the latest Illumina NovaSeq X/X Plus instruments with XLEAP chemistry. Here, we have run PCR-free whole genome sequencing on four human tumor cell lines using both Illumina NovaSeq X Plus and Element AVITI instruments. AVITI showed low duplication rates and reported higher base qualities, the latter contributed to improved mapping confidence and fewer spurious variant candidates. Both platforms were found to be highly comparable when benchmarking variant calling, with AVITI only providing a minor improvement on INDELs at lower coverages. Stratifying by genomic context revealed further differences, where AVITI genome coverage and variant calls were superior in high GC regions while being inferior in GC homopolymers. Error rate analysis highlighted further differences between the platforms, in particular AVITI in some instances displayed an increased error rate on read 2 related to short fragments. AVITI error rate was also found to be more stable downstream of repetitive regions, except for GC homopolymers. We further found that AVITI sequencing was sensitive to G-quadruplex motifs. Overall, despite these identified differences, both platforms performed highly comparable for variant analysis.

genomics↗

bioRxiv2018

High-resolution regulatory maps connect cardiovascular risk variants to disease related pathways

Genetic variant landscape of cardiovascular disease (CVD) is dominated by non-coding variants among which many occur within putative enhancers regulating the expression levels of relevant genes. It is crucial to assign the genetic variants to their correct gene both to gain insights into perturbed functions and better assess the risk of disease. In this study, we generated high-resolution genomic interaction maps (~750 bases) in aortic endothelial, smooth muscle and THP-1 macrophages using Hi-C coupled with sequence capture targeting 25,429 features including variants associated with CVD. We detected interactions for 761 CVD risk variants obtained by genome-wide association studies (GWAS) and identified novel as well as established functions associated with CVD. We were able to fine-map 331 GWAS variants using interaction networks, thereby identifying additional genes and functions. We also discovered a subset of risk variants interacting with multiple promoters and the expression levels of such genes were correlated. The presented resource enables functional studies of cardiovascular disease providing novel approaches for its diagnosis and treatment.

genomics↗