Biology subjects

Taborsak-Lines, F.

Publications and source records attributed to Taborsak-Lines, F..

3 recordsLinked to original sources

bioRxiv2024

Convergent and lineage-specific genomic changes contribute to adaptations in sugar-consuming birds

High-sugar diets cause human metabolic diseases, yet several bird lineages convergently adapted to feeding on sugar-rich nectar or fruits. We investigated the underlying molecular mechanisms in hummingbirds, parrots, honeyeaters, and sunbirds by generating nine new genomes and 90 tissue-specific transcriptomes. Comparative screens revealed an excess of repeated selection in both protein-coding and regulatory sequences in sugar-feeding birds, suggesting reuse of genetic elements. Sequence or expression changes in sugar-feeders affect genes involved in blood pressure regulation, lipid, amino acid and carbohydrate metabolism, with experiments showing functional changes in honeyeater hexokinase 3. MLXIPL, a key regulator of sugar and lipid homeostasis, showed convergent sequence and regulatory changes across all sugar-feeding clades; experiments revealed enhanced sugar-induced transcriptional activity of hummingbird MLXIPL, highlighting its adaptive role in high-sugar diets. Summary Figure: Our comparative screens across four independent sugar-feeding bird groups identified both repeated and lineage-specific targets of selection O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=65 SRC="FIGDIR/small/610474v2_ufig1.gif" ALT="Figure 1"> View larger version (24K): org.highwire.dtl.DTLVardef@148f5c8org.highwire.dtl.DTLVardef@1005dbaorg.highwire.dtl.DTLVardef@1097facorg.highwire.dtl.DTLVardef@9d365c_HPS_FORMAT_FIGEXP M_FIG C_FIG

evolutionary biology↗

bioRxiv2022

Enabling automated and reproducible spatially resolved transcriptomics at scale

Tissue spatial information is an essential component to reach a holistic overview of gene expression mechanisms. The sequencing-based Spatial transcriptomics approach allows to spatially barcode the whole transcriptome of tissue sections using microarray glass slides. However, manual preparation of high-quality tissue sequencing libraries is time-consuming and subjected to technical variability. Here, we present an automated adaptation of the 10x Genomics Visium library construction on the widely used Agilent Bravo Liquid Handling Platform. Compared to the manual Visium library preparation, our automated approach reduces hands-on time by over 80% and provides higher throughput and robustness. Our automated Visium library preparation protocol provides a new strategy to standardize spatially resolved transcriptomics analysis of tissues at scale.

genetics↗

bioRxiv2021

Linked-read whole-genome sequencing resolves common and private structural variants in multiple myeloma

Multiple myeloma (MM) is an incurable and aggressive plasma cell malignancy characterized by a complex karyotype with multiple structural variants (SVs) and copy number variations (CNVs). Linked-read whole-genome sequencing (lrWGS) allows for refined detection and reconstruction of SVs by providing long-range genetic information from standard short-read sequencing. This makes lrWGS an attractive solution for capturing the full genomic complexity of MM. Here we show that high-quality lrWGS data can be generated from low numbers of FACS sorted cells without DNA purification. Using this protocol, we analyzed FACS sorted MM cells from 37 MM patients with lrWGS. We found high concordance between lrWGS and FISH for the detection of recurrent translocations and CNVs. Outside of the regions investigated by FISH, we identified >150 additional SVs and CNVs across the cohort. Analysis of the lrWGS data allowed for resolving the structure of diverse SVs affecting the MYC and t(11;14) loci causing the duplication of genes and gene regulatory elements. In addition, we identified private SVs causing the dysregulation of genes recurrently involved in translocations with the IGH locus and show that these can alter the molecular classification of the MM. Overall, we conclude that lrWGS allows for the detection of aberrations critical for MM prognostics and provides a feasible route for providing comprehensive genetics. Implementing lrWGS could provide more accurate clinical prognostics, facilitate genomic medicine initiatives, and greatly improve the stratification of patients included in clinical trials. KEY POINTS- Linked-read WGS can be performed without DNA purification and allows for resolving the diverse structural variants found in multiple myeloma. - Linked-read WGS can, as a stand-alone assay, provide comprehensive genetics in myeloma and other diseases with complex genomes.

genetics↗