Bathina, M. | Search bioRxiv

bioRxiv2026

A rapid, sensitive, and quantitative high plex biomarker digital detection platform enabled by Hypercoding

Low-cost, multiplexed, and automated assays are needed to make omic technologies more broadly accessible in clinical, research, and commercial settings. We present Hypercoding, a scalable technology for detection and quantitation of multi-omic targets. Drawing from data reliability methods in the telecommunications field, Hypercoding uses fluorescent signals from hybridization with an error-correcting code to enable detection of high-plexity targets from biological samples, such as human DNA. In the presence of the target, a linear DNA construct is circularized, immobilized, and amplified to enable single-molecule detection of a target via rapid readout cycles within a 96-well plate. We demonstrate capability for >10,000 code plexity and accurate (98.7%) genotyping of 209 pharmacogenomic variants. Furthermore, we show computation of copy number variation with whole chromosome and sub-gene resolution, as well as quantitation of target abundance down to 10 fM sensitivity with a dynamic range of up to 10 logs.

genomics↗

bioRxiv2023

Inducible genetic ablation of Immt induces a lethal disruption of the MICOS complex

The mitochondrial contact site and cristae organizing system (MICOS) is important for cristae junctions (CJ) formation and for maintaining inner mitochondrial membrane (IMM) architecture. As the largest member, MIC60 is the primary scaffold protein for this complex. While MIC60 has been well studied in yeast and cell culture models, its function in mammals is poorly understood. To address this, we developed a mouse model conditionally deleting Immt (which encodes MIC60) and found that global Immt deletion disrupted the MICOS complex and resulted in lethality within 9 days of tamoxifen treatment. Pathologically, these mice display intestinal defects consistent with paralytic ileus, resulting in dehydration. We also identified bone marrow hypocellularity in tamoxifen-treated mice. However, bone marrow transplants from ImmtWT mice failed to rescue survival. Altogether, this novel mouse model demonstrates the importance of MIC60 in vivo, in both hematopoietic and non-hematopoietic tissues, and provides a valuable resource for future mechanistic investigations into the MICOS complex. Such investigations could include an in vivo structure-function analysis of MIC60 functional domains, with characterizations that are relevant to human diseases.

physiology↗