Katalin Susztak

Dec 16, 2024 | nature.com | Katalin Susztak

Diabetic kidney disease (DKD), the most common cause of chronic kidney disease, is primarily caused by metabolic dysfunction, likely due to mitochondrial abnormalities. In 2024, several studies made important strides towards defining the molecular mechanisms that underlie the development of DKD. Key advances A multi-omic and spatial metabolomic analysis of human kidney samples identified a defect in fatty acid oxidation in proximal tubule cells from people with kidney disease2.

Nov 26, 2024 | nature.com | Zhaojun Zhang |Divij Mathew |Tristan L. Lim |Kaishu Mason |Sijia Huang |E. John Wherry | +5 more

Data integration to align cells across batches has become a cornerstone of single-cell data analysis, critically affecting downstream results. Currently, there are no guidelines for when the biological differences between samples are separable from batch effects. Here we show that current paradigms for single-cell data integration remove biologically meaningful variation and introduce distortion. We present a statistical model and computationally scalable algorithm, CellANOVA (cell state space analysis of variance), that harnesses experimental design to explicitly recover biological signals that are erased during single-cell data integration. CellANOVA uses a ‘pool-of-controls’ design concept, applicable across diverse settings, to separate unwanted variation from biological variation of interest and allow the recovery of subtle biological signals. We apply CellANOVA to diverse contexts and validate the recovered biological signals by orthogonal assays. In particular, we show that CellANOVA is effective in the challenging case of single-cell and single-nucleus data integration, where it recovers subtle biological signals that can be validated and replicated by external data. A statistical framework quantifies single-cell batch variation and recovers meaningful biological signals.

Nov 5, 2024 | nature.com | Tanya J. Major |Riku Takei |Yuya Shirai |Wei Qing Wang |Murray Cadzow |Amanda Phipps-Green | +35 more

Correction to: Nature Genetics https://doi.org/10.1038/s41588-024-01921-5. Published online 15 October 2024. In the version of the article originally published, there were errors in the consortium lists at the end of the paper. Maureen Rischmueller, Hyon K. Choi, Masahiro Nakatochi, Jeff N. Miner, Daniel H. Solomon, Kathleen M. Giacomini and Deanna J. Brackman were erroneously listed as members of the Japan Gout Genomics Consortium.

Oct 15, 2024 | nature.com | Tanya J. Major |Riku Takei |Yuya Shirai |Wei Qing Wang |Murray Cadzow |Amanda Phipps-Green | +35 more

AbstractGout is a chronic disease that is caused by an innate immune response to deposited monosodium urate crystals in the setting of hyperuricemia. Here, we provide insights into the molecular mechanism of the poorly understood inflammatory component of gout from a genome-wide association study (GWAS) of 2.6 million people, including 120,295 people with prevalent gout. We detected 377 loci and 410 genetically independent signals (149 previously unreported loci in urate and gout).

Sep 17, 2024 | jci.org | Bernhard Dumoulin |Katalin Susztak |Konrad Hoeft |Sikander Hayat

AbstractFibrosis is a common manifestation of most progressive and degenerative diseases, with myofibroblast activation and matrix accumulation playing a key role. In this issue of the JCI, Hoeft et al. identify the important role of ADAMTS12 in fibroblast activation. ADAMTS12, a secreted protein, is involved in extracellular matrix (ECM) remodeling, cell signaling, and inflammation.