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Results 21 through 40 out of 2546

in category systems biology


21: Differential stoichiometry among core ribosomal proteins

Nikolai Slavov

5,129 downloads (posted 26 May 2014)

Understanding the regulation and structure of ribosomes is essential to understanding protein synthesis and its dysregulation in disease. While ribosomes are believed to have a fixed stoichiometry among their core ribosomal proteins (RPs), some experiments suggest a more variable composition. Testing such variability requires direct and precise quantification of RPs. We used mass-spectrometry to directly quantify RPs across monosomes and polysomes of mouse embryonic stem cells (ESC) and budding yeast. Our data show that the stoichiometry among core RPs in wild-type yeast cells and ESC depends both on the growth conditions and on the number of ribosomes bound per mRNA. Furthermore, we find that the fitness of cells with a deleted RP-gene is inversely proportional to the enrichment of the corresponding RP in polysomes. Together, our findings support the existence of ribosomes with distinct protein composition and physiological function.


22: Massively parallel clonal analysis using CRISPR/Cas9 induced genetic scars

Jan Philipp Junker, Bastiaan Spanjaard et al.

5,086 downloads (posted 01 Jun 2016)

A key goal of developmental biology is to understand how a single cell transforms into a full-grown organism consisting of many cells. Although impressive progress has been made in lineage tracing using imaging approaches, analysis of vertebrate lineage trees has mostly been limited to relatively small subsets of cells. Here we present scartrace, a strategy for massively parallel clonal analysis based on Cas9 induced genetic scars in the zebrafish.


23: Mechanistic modelling and Bayesian inference elucidates the variable dynamics of double-strand break repair

M. Woods, Chris Barnes

4,788 downloads (posted 04 Sep 2015)

DNA double-strand breaks are lesions that form during metabolism, DNA replication and exposure to mutagens. When a double-strand break occurs one of a number of repair mechanisms is recruited, all of which have differing propensities for mutational events. Despite DNA repair being of crucial importance, the relative contribution of these mechanisms and their regulatory interactions remain to be fully elucidated. Understanding these mutational processes will have a profound impact on our knowledge of genomic instability,...


24: Bulk and single-cell gene expression profiling of SARS-CoV-2 infected human cell lines identifies molecular targets for therapeutic intervention

Emanuel Wyler, Mösbauer Kirstin et al.

4,756 downloads (posted 05 May 2020)

The coronavirus disease 2019 (COVID-19) pandemic, caused by the novel severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is an ongoing global health threat with more than two million infected people since its emergence in late 2019. Detailed knowledge of the molecular biology of the infection is indispensable for understanding of the viral replication, host responses, and disease progression. We provide gene expression profiles of SARS-CoV and SARS-CoV-2 infections in three human cell lines (H1299, Caco-2 and...


25: Charting a tissue from single-cell transcriptomes

Mor Nitzan, Nikos Karaiskos et al.

4,693 downloads (posted 30 Oct 2018)

Massively multiplexed sequencing of RNA in individual cells is transforming basic and clinical life sciences. However, in standard experiments, tissues must first be dissociated. Thus, after sequencing, information about the spatial relationships between cells is lost although this knowledge is crucial for understanding cellular and tissue-level function. Recent attempts to overcome this fundamental challenge rely on employing additional in situ gene expression imaging data which can guide spatial mapping of sequenced c...


26: Memory sequencing reveals heritable single cell gene expression programs associated with distinct cellular behaviors

Sydney M. Shaffer, Benjamin L. Emert et al.

4,441 downloads (posted 27 Jul 2018)

Non-genetic factors can cause individual cells to fluctuate substantially in gene expression levels over time. Yet it remains unclear whether these fluctuations can persist for much longer than the time of one cell division. Current methods for measuring gene expression in single cells mostly rely on single time point measurements, making the duration of gene expression fluctuations or cellular memory difficult to measure. Here, we report a method combining Luria and Delbrück’s fluctuation analysis with population-based...


27: Undulating changes in human plasma proteome across lifespan are linked to disease

Benoit Lehallier, David Gate et al.

4,381 downloads (posted 01 Sep 2019)

Aging is the predominant risk factor for numerous chronic diseases that limit healthspan. Mechanisms of aging are thus increasingly recognized as therapeutic targets. Blood from young mice reverses aspects of aging and disease across multiple tissues, pointing to the intriguing possibility that age-related molecular changes in blood can provide novel insight into disease biology. We measured 2,925 plasma proteins from 4,331 young adults to nonagenarians and developed a novel bioinformatics approach which uncovered profo...


28: Piper longum: A review of its phytochemicals and their network pharmacological evaluation

Neha Choudhary, Vikram Singh

4,314 downloads (posted 04 Aug 2017)

Piper longum L. (P. longum, also called as long pepper) is one of the common culinary herb and has been extensively used as an important constituent of various indigenous medicines, specifically in traditional Indian medicinal system known as Ayurveda. Towards obtaining a global regulatory framework of P. longum's constituents, in this work we first reviewed phytochemicals present in this herb and then studied their pharmacological and medicinal features using network pharmacology approach. We developed high-confidence ...


29: DeepWAS: Multivariate genotype-phenotype associations by directly integrating regulatory information using deep learning

Janine Arloth, Gökcen Eraslan et al.

4,201 downloads (posted 11 Aug 2016)

Genome-wide association studies (GWAS) identify genetic variants associated with quantitative traits or disease. Thus, GWAS never directly link variants to regulatory mechanisms, which, in turn, are typically inferred during post-hoc analyses. In parallel, a recent deep learning-based method allows for prediction of regulatory effects per variant on currently up to 1,000 cell type-specific chromatin features. We here describe "DeepWAS", a new approach that directly integrates predictions of these regulatory effects of s...


30: Evaluation and Design of Genome-wide CRISPR/Cas9 Knockout Screens

Traver Hart, Amy Tong et al.

4,187 downloads (posted 16 Mar 2017)

The adaptation of CRISPR/Cas9 technology to mammalian cell lines is transforming the study of human functional genomics. Pooled libraries of CRISPR guide RNAs (gRNAs), targeting human protein-coding genes and encoded in viral vectors, have been used to systematically create gene knockouts in a variety of human cancer and immortalized cell lines, in an effort to identify whether these knockouts cause cellular fitness defects. Previous work has shown that CRISPR screens are more sensitive and specific than pooled library ...


31: A deep proteome and transcriptome abundance atlas of 29 healthy human tissues

Dongxue Wang, Basak Eraslan et al.

4,085 downloads (posted 27 Jun 2018)

Genome-, transcriptome- and proteome-wide measurements provide valuable insights into how biological systems are regulated. However, even fundamental aspects relating to which human proteins exist, where they are expressed and in which quantities are not fully understood. Therefore, we have generated a systematic, quantitative and deep proteome and transcriptome abundance atlas from 29 paired healthy human tissues from the Human Protein Atlas Project and representing human genes by 17,615 transcripts and 13,664 proteins...


32: Transcriptional burst initiation and polymerase pause release are key control points of transcriptional regulation

Caroline Bartman, Cheryl A. Keller et al.

3,811 downloads (posted 02 Mar 2018)

Transcriptional regulation occurs via changes to the rates of various biochemical processes. Sequencing based approaches that average together many cells have suggested that polymerase binding and polymerase release from promoter proximal pausing are two key regulated steps in the transcriptional process. However, single cell studies have revealed that transcription occurs in short, discontinuous bursts, suggesting that transcriptional burst initiation and termination might also be regulated steps. Here, we develop and ...


33: Full-length mRNA sequencing reveals principles of poly(A) tail length control

Ivano Legnini, Jonathan Alles et al.

3,741 downloads (posted 11 Feb 2019)

Although mRNAs are key molecules for understanding life, there exists no method to determine the full-length sequence of endogenous mRNAs including their poly(A) tails. Moreover, although poly(A) tails can be modified in functionally important ways, there also exists no method to accurately sequence them. Here, we present FLAM-seq, a rapid and simple method for high-quality sequencing of entire mRNAs. We report a cDNA library preparation method coupled to single-molecule sequencing to perform FLAM-seq. Using human cell ...


34: Longitudinal single cell transcriptomics reveals Krt8+ alveolar epithelial progenitors in lung regeneration

Maximilian Strunz, Lukas M. Simon et al.

3,670 downloads (posted 17 Jul 2019)

Lung injury activates quiescent stem and progenitor cells to regenerate alveolar structures. The sequence and coordination of transcriptional programs during this process has largely remained elusive. Using single cell RNA-seq, we first generated a whole-organ bird’s-eye view on cellular dynamics and cell-cell communication networks during mouse lung regeneration from ~30,000 cells at six timepoints. We discovered an injury-specific progenitor cell state characterized by Krt8 in flat epithelial cells covering alveolar s...


35: Cell-Type Selective Markers Represented in Whole-Kidney RNA-Seq Data

Jevin Z Clark, Lihe Chen et al.

3,617 downloads (posted 15 Jun 2018)

Bulk-tissue RNA-Seq is seeing increasing use in the study of physiological and pathophysiological processes in the kidney. However, the presence of multiple cell types in kidney complicates the interpretation of the data. Here we address the question, What cell types are represented in whole-kidney RNA-Seq data? to identify circumstances in which bulk-kidney RNA-Seq can successfully be interpreted. We carried out RNA-Seq in mouse whole kidneys and microdissected proximal S2 segments. To aid in the interpretation of the ...


36: Parallel accumulation – serial fragmentation combined with data-independent acquisition (diaPASEF): Bottom-up proteomics with near optimal ion usage

Florian Meier, Andreas-David Brunner et al.

3,555 downloads (posted 31 May 2019)

Data independent acquisition (DIA) modes isolate and concurrently fragment populations of different precursors by cycling through segments of a predefined precursor m/z range. Although these selection windows collectively cover the entire m/z range, overall only a few percent of all incoming ions are sampled. Making use of the correlation of molecular weight and ion mobility in a trapped ion mobility device (timsTOF Pro), we here devise a novel scan mode that samples up to 100% of the peptide precursor ion current. We e...


37: A single-cell RNA expression map of human coronavirus entry factors

Manvendra Singh, Vikas Bansal et al.

3,451 downloads (posted 09 May 2020)

To predict the tropism of human coronaviruses, we profile 28 SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs) using single-cell RNA-sequencing data from a wide range of healthy human tissues. SCARFs include cellular factors both facilitating and restricting viral entry. Among adult organs, enterocytes and goblet cells of the small intestine and colon, kidney proximal tubule cells, and gallbladder basal cells appear most permissive to SARS-CoV-2, consistent with clinical data. Our analysis also sugges...


38: Determining protein structures using genetics

Jörn M. Schmiedel, Ben Lehner

3,426 downloads (posted 20 Apr 2018)

Determining the three dimensional structures of macromolecules is a major goal of biological research because of the close relationship between structure and function. Structure determination usually relies on physical techniques including x-ray crystallography, NMR spectroscopy and cryo-electron microscopy. Here we present a method that allows the high-resolution three-dimensional structure of a biological macromolecule to be determined only from measurements of the activity of mutant variants of the molecule. This gen...


39: A compound that directly and selectively stalls PCSK9 translation

Nathanael G. Lintner, Kim F. McClure et al.

3,335 downloads (posted 25 Oct 2016)

Proprotein Convertase Subtilisin/Kexin Type 9 (PCSK9) plays a key role in regulating the levels of plasma low density lipoprotein cholesterol (LDL-C). Here we demonstrate that the compound PF-06446846 inhibits translation of PCSK9 by inducing the ribosome to stall around codon 34, mediated by the sequence of the nascent chain within the exit tunnel. We further show that PF-06446846 reduces plasma PCSK9 and total cholesterol levels in rats following oral dosing. Using ribosome profiling, we demonstrate that PF-06446846 i...


40: Cell Painting, a high-content image-based assay for morphological profiling using multiplexed fluorescent dyes

Mark-Anthony Bray, Shantanu Singh et al.

3,326 downloads (posted 25 Apr 2016)

In morphological profiling, quantitative data are extracted from microscopy images of cells to identify biologically relevant similarities and differences among samples based on these profiles. This protocol describes the design and execution of experiments using Cell Painting, a morphological profiling assay multiplexing six fluorescent dyes imaged in five channels, to reveal eight broadly relevant cellular components or organelles. Cells are plated in multi-well plates, perturbed with the treatments to be tested, stai...