Optocoder: computational decoding of spatially indexed bead arrays

Advancing technologies that quantify gene expression in space are transforming contemporary biology research. A class of spatial transcriptomics methods uses barcoded bead arrays that are optically decoded via microscopy and are later matched to sequenced data from the respective libraries. To obtain a detailed representation of the tissue in space, robust and efficient computational pipelines are required to process microscopy images and accurately basecall the bead barcodes. Optocoder is a computational framework that processes microscopy images to decode bead barcodes in space. It efficiently aligns images, detects beads, and corrects for confounding factors of the fluorescence signal, such as crosstalk and phasing. Furthermore, Optocoder employs supervised machine learning to strongly increase the number of matches between optically decoded and sequenced barcodes. We benchmark Optocoder using data from an in-house spatial transcriptomics platform, as well as from Slide-Seq(V2), and we show that it efficiently processes all datasets without modification. Optocoder is publicly available, open-source and provided as a stand-alone Python package on GitHub: https://github.com/rajewsky-lab/optocoder

Introduction to Quantum Integrability

In this article we review the basic concepts regarding quantum integrability. Special emphasis is given on the algebraic content of integrable models. The associated algebras are essentially described by the Yang-Baxter and boundary Yang-Baxter equations depending on the choice of boundary conditions. The relation between the aforementioned equations and the braid group is briefly discussed. A short review on quantum groups as well as the quantum inverse scattering method (algebraic Bethe ansatz) is also presented.Comment: 56 pages, Latex. A few typos correcte

Spacemake: processing and analysis of large-scale spatial transcriptomics data

BACKGROUND: Spatial sequencing methods increasingly gain popularity within RNA biology studies. State-of-the-art techniques quantify messenger RNA expression levels from tissue sections and at the same time register information about the original locations of the molecules in the tissue. The resulting data sets are processed and analyzed by accompanying software that, however, is incompatible across inputs from different technologies. FINDINGS: Here, we present spacemake, a modular, robust, and scalable spatial transcriptomics pipeline built in Snakemake and Python. Spacemake is designed to handle all major spatial transcriptomics data sets and can be readily configured for other technologies. It can process and analyze several samples in parallel, even if they stem from different experimental methods. Spacemake's unified framework enables reproducible data processing from raw sequencing data to automatically generated downstream analysis reports. Spacemake is built with a modular design and offers additional functionality such as sample merging, saturation analysis, and analysis of long reads as separate modules. Moreover, spacemake employs novoSpaRc to integrate spatial and single-cell transcriptomics data, resulting in increased gene counts for the spatial data set. Spacemake is open source and extendable, and it can be seamlessly integrated with existing computational workflows

Holographic Kondo Model in Various Dimensions

We study the addition of localised impurities to U(N) Supersymmetric Yang-Mills theories in (p+1)-dimensions by using the gauge/gravity correspondence. From the gravity side, the impurities are introduced by considering probe D(8-p)-branes extendingalong the time and radial directions and wrapping an (7-p)-dimensional submanifold of the internal (8-p)-sphere, so that the degrees of freedom are point-like from the gauge theory perspective. We analyse both the configuration in which the branes generate straight flux tubes -corresponding to actual single impurities - and the one in which connected flux tubes are created- corresponding to dimers. We discuss the thermodynamics of both the configurations and the related phase transition. In particular, the specific heat of the straight flux-tube configuration is negative for p<3, while it is never the case for the connected one. We study the stability of the system by looking at the impurity fluctuations. Finally, we characterise the theory by computing one- and two-point correlators of the gauge theory operators dual to the impurity fluctuations. Because of the underlying generalised conformal structure, such correlators can be expressed in terms of an effective coupling constant (which runs because of its dimensionality) and a generalised conformal dimension.Comment: 56 pages, 3 figures; v2: typos correcte

New reflection matrices for the U_q(gl(m|n)) case

We examine super symmetric representations of the B-type Hecke algebra. We exploit such representations to obtain new non-diagonal solutions of the reflection equation associated to the super algebra U_q(gl(m|n)). The boundary super algebra is briefly discussed and it is shown to be central to the super symmetric realization of the B-type Hecke algebraComment: 13 pages, Latex. A few alterations regarding the representations. A reference adde

Human muscle-derived CLEC14A-positive cells regenerate muscle independent of PAX7

Skeletal muscle stem cells, called satellite cells and defined by the transcription factor PAX7, are responsible for postnatal muscle growth, homeostasis and regeneration. Attempts to utilize the regenerative potential of muscle stem cells for therapeutic purposes so far failed. We previously established the existence of human PAX7-positive cell colonies with high regenerative potential. We now identified PAX7-negative human muscle-derived cell colonies also positive for the myogenic markers desmin and MYF5. These include cells from a patient with a homozygous PAX7 c.86-1G > A mutation (PAX7null). Single cell and bulk transcriptome analysis show high intra- and inter-donor heterogeneity and reveal the endothelial cell marker CLEC14A to be highly expressed in PAX7null cells. All PAX7-negative cell populations, including PAX7null, form myofibers after transplantation into mice, and regenerate muscle after reinjury. Transplanted PAX7neg cells repopulate the satellite cell niche where they re-express PAX7, or, strikingly, CLEC14A. In conclusion, transplanted human cells do not depend on PAX7 for muscle regeneration

Single-cell transcriptomics reveals common epithelial response patterns in human acute kidney injury

BACKGROUND: Acute kidney injury (AKI) occurs frequently in critically ill patients and is associated with adverse outcomes. Cellular mechanisms underlying AKI and kidney cell responses to injury remain incompletely understood. METHODS: We performed single-nuclei transcriptomics, bulk transcriptomics, molecular imaging studies, and conventional histology on kidney tissues from 8 individuals with severe AKI (stage 2 or 3 according to Kidney Disease: Improving Global Outcomes (KDIGO) criteria). Specimens were obtained within 1-2 h after individuals had succumbed to critical illness associated with respiratory infections, with 4 of 8 individuals diagnosed with COVID-19. Control kidney tissues were obtained post-mortem or after nephrectomy from individuals without AKI. RESULTS: High-depth single cell-resolved gene expression data of human kidneys affected by AKI revealed enrichment of novel injury-associated cell states within the major cell types of the tubular epithelium, in particular in proximal tubules, thick ascending limbs, and distal convoluted tubules. Four distinct, hierarchically interconnected injured cell states were distinguishable and characterized by transcriptome patterns associated with oxidative stress, hypoxia, interferon response, and epithelial-to-mesenchymal transition, respectively. Transcriptome differences between individuals with AKI were driven primarily by the cell type-specific abundance of these four injury subtypes rather than by private molecular responses. AKI-associated changes in gene expression between individuals with and without COVID-19 were similar. CONCLUSIONS: The study provides an extensive resource of the cell type-specific transcriptomic responses associated with critical illness-associated AKI in humans, highlighting recurrent disease-associated signatures and inter-individual heterogeneity. Personalized molecular disease assessment in human AKI may foster the development of tailored therapies

Geographical variation in therapy for bloodstream infections due to multidrug-resistant enterobacteriaceae: a post hoc analysis of the INCREMENT study

We aimed to describe regional differences in therapy for bloodstream infection (BSI) caused by extended-spectrum ?-lactamase-producing Enterobacteriaceae (ESBL-E) or carbapenemase-producing Enterobacteriaceae (CPE). 1,482 patients in 12 countries were included from an observational study of BSI caused by ESBL-E or CPE. Multivariate logistic regression was used to calculate adjusted odds ratios (aORs) for the influence of country of recruitment on empirical use of ?-lactam/?-lactamase inhibitors (BLBLI) or carbapenems, targeted use of BLBLI for ESBL-E and use of targeted combination therapy for CPE. The use of BLBLI for empirical therapy was least likely in sites from Israel (aOR 0.34, 95% CI 0.14-0.81), Greece (aOR 0.49, 95% CI 0.26-0.94) and Canada (aOR 0.31, 95% CI 0.11-0.88) but more likely in Italy (aOR 1.58, 95% CI 1.11-2.2) and Turkey (aOR 2.09, 95% CI 1.14-3.81), compared to Spain as a reference. Empirical carbapenems were more likely to be used in sites from Taiwan (aOR 1.73, 95% CI 1.03-2.92) and USA (aOR 1.89; 95% CI 1.05-3.39), and less likely in Italy (aOR 0.44, 95% CI 0.28-0.69) and Canada (aOR 0.10, 95% CI 0.01-0.74). Targeted BLBLI for ESBL-E was more likely in sites from Italy. Treatment at sites within Israel, Taiwan, Turkey and Brazil was associated with less combination therapy for CPE. Although this study does not provide precise data on the relative prevalence of ESBL-E or CPE, significant variation in therapy exists across countries even after adjustment for patient factors. A better understanding of what influences therapeutic choices for these infections will aid antimicrobial stewardship efforts.PH is supported by an Australian Postgraduate Award from the University of Queensland. The study was funded by the Ministerio de Economía y Competitividad, Instituto de Salud Carlos III - co-financed by European Development Regional Fund "A way to achieve Europe" ERDF, Spanish Network for the Research in Infectious Diseases (REIPI RD12/0015). BGG, JRB, APH and YC also received funds from the COMBACTE-CARE project (grant agreement 115620), Innovative Medicines Initiative (IMI), the European Union's Seventh Framework Programme (FP7/2007-2013) and in-kind contributions from EFPIA companies