DGRPool, a web tool leveraging harmonized Genetic Reference Panel phenotyping data for the study of complex traits.

Genome-wide association studies have advanced our understanding of complex traits, but studying how a GWAS variant can affect a specific trait in the human population remains challenging due to environmental variability. is in this regard an excellent model organism for studying the relationship between genetic and phenotypic variation due to its simple handling, standardized growth conditions, low cost, and short lifespan. The Genetic Reference Panel (DGRP) in particular has been a valuable tool for studying complex traits, but proper harmonization and indexing of DGRP phenotyping data is necessary to fully capitalize on this resource.

Fly Cell Atlas: A single-nucleus transcriptomic atlas of the adult fruit fly.

For more than 100 years, the fruit fly has been one of the most studied model organisms. Here, we present a single-cell atlas of the adult fly, Tabula , that includes 580,000 nuclei from 15 individually dissected sexed tissues as well as the entire head and body, annotated to >250 distinct cell types. We provide an in-depth analysis of cell type-related gene signatures and transcription factor markers, as well as sexual dimorphism, across the whole animal.

SPICA: Swiss portal for immune cell analysis.

Single-cell transcriptomics allows the study of immune cell heterogeneity at an unprecedented level of resolution. The Swiss portal for immune cell analysis (SPICA) is a web resource dedicated to the exploration and analysis of single-cell RNA-seq data of immune cells. In contrast to other single-cell databases, SPICA hosts curated, cell type-specific reference atlases that describe immune cell states at high resolution, and published single-cell datasets analysed in the context of these atlases.

Spatial tissue profiling by imaging-free molecular tomography.

Several techniques are currently being developed for spatially resolved omics profiling, but each new method requires the setup of specific detection strategies or specialized instrumentation. Here we describe an imaging-free framework to localize high-throughput readouts within a tissue by cutting the sample into thin strips in a way that allows subsequent image reconstruction. We implemented this framework to transform a low-input RNA sequencing protocol into an imaging-free spatial transcriptomics technique (called STRP-seq) and validated it by profiling the spatial transcriptome of the mouse brain.

Systematic analysis of differential rhythmic liver gene expression mediated by the circadian clock and feeding rhythms.

The circadian clock and feeding rhythms are both important regulators of rhythmic gene expression in the liver. To further dissect the respective contributions of feeding and the clock, we analyzed differential rhythmicity of liver tissue samples across several conditions. We developed a statistical method tailored to compare rhythmic liver messenger RNA (mRNA) expression in mouse knockout models of multiple clock genes, as well as PARbZip output transcription factors (//).

Ether lipids, sphingolipids and toxic 1-deoxyceramides as hallmarks for lean and obese type 2 diabetic patients.

Aim: The worldwide increase in obesity and type 2 diabetes (T2D) represents a major health challenge. Chronically altered lipids induced by obesity further promote the development of T2D, and the accumulation of toxic lipid metabolites in serum and peripheral organs may contribute to the diabetic phenotype.

Methods: To better understand the complex metabolic pattern of lean and obese T2D and non-T2D individuals, we analysed the lipid profile of human serum, skeletal muscle and visceral adipose tissue of two cohorts by systematic mass spectrometry-based lipid analysis.

ASAP 2020 update: an open, scalable and interactive web-based portal for (single-cell) omics analyses.

Single-cell omics enables researchers to dissect biological systems at a resolution that was unthinkable just 10 years ago. However, this analytical revolution also triggered new demands in 'big data' management, forcing researchers to stay up to speed with increasingly complex analytical processes and rapidly evolving methods. To render these processes and approaches more accessible, we developed the web-based, collaborative portal ASAP (Automated Single-cell Analysis Portal).

Identifying gene function and module connections by the integration of multispecies expression compendia.

The functions of many eukaryotic genes are still poorly understood. Here, we developed and validated a new method, termed GeneBridge, which is based on two linked approaches to impute gene function and bridge genes with biological processes. First, ene-odule ssociation etermination (G-MAD) allows the annotation of gene function.

SwissPalm 2: Protein S-Palmitoylation Database.

Protein S-palmitoylation is increasingly recognized as an important posttranslational modification, present in all eukaryotic organisms, involved in the regulation of many biological processes. The SwissPalm database centralizes the large and increasing number of published palmitoyl-proteome datasets, provides tools to compare them, and includes curated data from the literature on the identification and analysis of palmitoylated proteins. SwissPalm 2 provides an updated version, with 38 palmitoyl-proteomes at the time of release, from 17 different species, and new features such as the inclusion of orthologs.

Mitochondria-specific photoactivation to monitor local sphingosine metabolism and function.

Photoactivation ('uncaging') is a powerful approach for releasing bioactive small-molecules in living cells. Current uncaging methods are limited by the random distribution of caged molecules within cells. We have developed a mitochondria-specific photoactivation method, which permitted us to release free sphingosine inside mitochondria and thereafter monitor local sphingosine metabolism by lipidomics.

The SAGA complex, together with transcription factors and the endocytic protein Rvs167p, coordinates the reprofiling of gene expression in response to changes in sterol composition in .

Changes in cellular sterol species and concentrations can have profound effects on the transcriptional profile. In yeast, mutants defective in sterol biosynthesis show a wide range of changes in transcription, including a coinduction of anaerobic genes and ergosterol biosynthesis genes, biosynthesis of basic amino acids, and several stress genes. However the mechanisms underlying these changes are unknown.

ASAP: a web-based platform for the analysis and interactive visualization of single-cell RNA-seq data.

Motivation: Single-cell RNA-sequencing (scRNA-seq) allows whole transcriptome profiling of thousands of individual cells, enabling the molecular exploration of tissues at the cellular level. Such analytical capacity is of great interest to many research groups in the world, yet these groups often lack the expertise to handle complex scRNA-seq datasets.

Results: We developed a fully integrated, web-based platform aimed at the complete analysis of scRNA-seq data post genome alignment: from the parsing, filtering and normalization of the input count data files, to the visual representation of the data, identification of cell clusters, differentially expressed genes (including cluster-specific marker genes), and functional gene set enrichment.

GETPrime 2.0: gene- and transcript-specific qPCR primers for 13 species including polymorphisms.

GETPrime (http://bbcftools.epfl.ch/getprime) is a database with a web frontend providing gene- and transcript-specific, pre-computed qPCR primer pairs.

Extension of least squares spectral resolution algorithm to high-resolution lipidomics data.

Lipidomics, which focuses on the global study of molecular lipids in biological systems, has been driven tremendously by technical advances in mass spectrometry (MS) instrumentation, particularly high-resolution MS. This requires powerful computational tools that handle the high-throughput lipidomics data analysis. To address this issue, a novel computational tool has been developed for the analysis of high-resolution MS data, including the data pretreatment, visualization, automated identification, deconvolution and quantification of lipid species.

SwissPalm: Protein Palmitoylation database.

Protein S-palmitoylation is a reversible post-translational modification that regulates many key biological processes, although the full extent and functions of protein S-palmitoylation remain largely unexplored. Recent developments of new chemical methods have allowed the establishment of palmitoyl-proteomes of a variety of cell lines and tissues from different species.  As the amount of information generated by these high-throughput studies is increasing, the field requires centralization and comparison of this information.

The SwissLipids knowledgebase for lipid biology.

Motivation: Lipids are a large and diverse group of biological molecules with roles in membrane formation, energy storage and signaling. Cellular lipidomes may contain tens of thousands of structures, a staggering degree of complexity whose significance is not yet fully understood. High-throughput mass spectrometry-based platforms provide a means to study this complexity, but the interpretation of lipidomic data and its integration with prior knowledge of lipid biology suffers from a lack of appropriate tools to manage the data and extract knowledge from it.

Systematic lipidomic analysis of yeast protein kinase and phosphatase mutants reveals novel insights into regulation of lipid homeostasis.

The regulatory pathways required to maintain eukaryotic lipid homeostasis are largely unknown. We developed a systematic approach to uncover new players in the regulation of lipid homeostasis. Through an unbiased mass spectrometry-based lipidomic screening, we quantified hundreds of lipid species, including glycerophospholipids, sphingolipids, and sterols, from a collection of 129 mutants in protein kinase and phosphatase genes of Saccharomyces cerevisiae.

HTSstation: a web application and open-access libraries for high-throughput sequencing data analysis.

The HTSstation analysis portal is a suite of simple web forms coupled to modular analysis pipelines for various applications of High-Throughput Sequencing including ChIP-seq, RNA-seq, 4C-seq and re-sequencing. HTSstation offers biologists the possibility to rapidly investigate their HTS data using an intuitive web application with heuristically pre-defined parameters. A number of open-source software components have been implemented and can be used to build, configure and run HTS analysis pipelines reactively.

Morphological and molecular characterization of adult midgut compartmentalization in Drosophila.

Although the gut is a central organ of Eumetazoans and is essential for organismal health, our understanding of its morphological and molecular determinants remains rudimentary. Here, we provide a comprehensive atlas of Drosophila adult midgut. Specifically, we uncover a fine-grained regional organization consisting of 14 subregions with distinct morphological, histological, and genetic properties.

Glycosylphosphatidylinositol anchors regulate glycosphingolipid levels.

Glycosylphosphatidylinositol (GPI) anchor biosynthesis takes place in the endoplasmic reticulum (ER). After protein attachment, the GPI anchor is transported to the Golgi where it undergoes fatty acid remodeling. The ER exit of GPI-anchored proteins is controlled by glycan remodeling and p24 complexes act as cargo receptors for GPI anchor sorting into COPII vesicles.

Activation of the unfolded protein response pathway causes ceramide accumulation in yeast and INS-1E insulinoma cells.

Sphingolipids are not only important components of membranes but also have functions in protein trafficking and intracellular signaling. The LCB1 gene encodes a subunit of the serine palmitoyltransferase, which is responsible for the first step of sphingolipid synthesis. Here, we show that activation of the unfolded protein response (UPR) can restore normal ceramide levels and viability in yeast cells with a conditional defect in LCB1.

GETPrime: a gene- or transcript-specific primer database for quantitative real-time PCR.

The vast majority of genes in humans and other organisms undergo alternative splicing, yet the biological function of splice variants is still very poorly understood in large part because of the lack of simple tools that can map the expression profiles and patterns of these variants with high sensitivity. High-throughput quantitative real-time polymerase chain reaction (qPCR) is an ideal technique to accurately quantify nucleic acid sequences including splice variants. However, currently available primer design programs do not distinguish between splice variants and also differ substantially in overall quality, functionality or throughput mode.

Easy retrieval of single amino-acid polymorphisms and phenotype information using SwissVar.

Summary: The SwissVar portal provides access to a comprehensive collection of single amino acid polymorphisms and diseases in the UniProtKB/Swiss-Prot database via a unique search engine. In particular, it gives direct access to the newly improved Swiss-Prot variant pages. The key strength of this portal is that it provides a possibility to query for similar diseases, as well as the underlying protein products and the molecular details of each variant.

Ribosome association and stability of the nascent polypeptide-associated complex is dependent upon its own ubiquitination.

In this work we addressed the role of ubiquitination in the function of the nascent polypeptide-associated complex (NAC), named EGD in the yeast Saccharomyces cerevisiae. To this end, we first identified the lysines residues required for ubiquitination of EGD/NAC. While simultaneous mutation of many lysines in the alpha-subunit of NAC (Egd2p) was required to abolish its ubiquitination, for the beta-subunit of NAC (Egd1p), mutation of K29 and K30 was sufficient.

Enrichment of N-terminal cysteinyl-peptides by covalent capture.

The detection of low abundance proteins in complex biological samples is still a challenge in proteomics. To circumvent this obstacle a number of strategies involving the targeting of subsets of proteins or peptides were developed. The following work describes a new approach to simplify peptide mixtures by enrichment of N-terminal cysteinyl peptides (and to some extent N-terminal threonine peptides).