Biology subjects

Handzlik, J. E.

Publications and source records attributed to Handzlik, J. E..

2 recordsLinked to original sources

bioRxiv2021

Data-driven modeling predicts gene regulatory network dynamics during the differentiation of multipotential progenitors

Cellular differentiation during hematopoiesis is guided by gene regulatory networks (GRNs) thought to be organized as a hierarchy of bistable switches, with antagonism between Gata1 and PU.1 driving red- and white-blood cell differentiation. We utilized high temporal-resolution gene-expression data from in vitro erythrocyte-neutrophil differentiation and a predictive data-driven dynamical modeling framework to learn the architecture and dynamics of gene regulation in a comprehensive twelve-gene GRN. The inferred genetic architecture is densely interconnected rather than hierarchical. The analysis of model dynamics revealed that neutrophil differentiation is driven by C/EBP and Gfi1 rather than PU.1. This prediction is supported by the sequence of gene up-regulation in an independent mouse bone marrow scRNA-Seq dataset. These results imply that neutrophil differentiation is not driven by the Gata1-PU.1 switch but by neutrophil-specific genes instead. More generally, this work shows that data-driven dynamical modeling can uncover the causality of developmental events that might otherwise be obscured.

systems biology↗

bioRxiv2019

Manatee: detection and quantification of small ncRNAs from next-generation sequencing data

Small non-coding RNAs (sncRNAs) play important roles in health and disease. Next Generation Sequencing technologies are considered as the most powerful and versatile methodologies to explore small RNA (sRNA) transcriptomes in diverse experimental and clinical studies. Small RNA-Seq data analysis proved to be challenging due to non-unique genomic origin, short length and abundant post-transcriptional modifications of sRNA species. Here we present Manatee, an algorithm for quantification of sRNA classes and detection of uncharacterized expressed non-coding loci. Manatee adopts a novel approach for abundance estimation of genomic reads that combines sRNA annotation with reliable alignment density information and extensive reads salvation. Comparison of Manatee against state-of-the-art implementations using real/simulated data sets demonstrates its superior accuracy in quantification of diverse sRNA classes providing at the same time insights about unannotated expressed loci. It is user-friendly, easily embeddable in pipelines and provides a simplified output suitable for direct usage in downstream analyses and functional studies.

bioinformatics↗