Biology subjects

Hao, M.

Publications and source records attributed to Hao, M..

42 records · Page 3Linked to original sources

bioRxiv2020

SOMDE: A scalable method for identifying spatially variable genes with self-organizing map

Recent developments of spatial transcriptomic sequencing technologies provide powerful tools for understanding cells in the physical context of tissue micro-environments. A fundamental task in spatial gene expression analysis is to identify genes with spatially variable expression patterns, or spatially variable genes (SVgenes). Several computational methods have been developed for this task. Their high computational complexity limited their scalability to the latest and future large-scale spatial expression data. We present SOMDE, an efficient method for identifying SVgenes in large-scale spatial expression data. SOMDE uses self-organizing map (SOM) to cluster neighboring cells into nodes, and then uses a Gaussian Process to fit the node-level spatial gene expression to identify SVgenes. Experiments show that SOMDE is about 5-50 times faster than existing methods with comparable results. The adjustable resolution of SOMDE makes it the only method that can give results in [~]5 minutes in large datasets of more than 20,000 sequencing sites. SOMDE is available as a python package on PyPI at https://pypi.org/project/somde free for academic use.

bioinformatics↗

bioRxiv2020

A potent neutralizing human antibody reveals the N-terminal domain of the Spike protein of SARS-CoV-2 as a site of vulnerability

The pandemic of coronavirus disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) presents a global public health threat. Most research on therapeutics against SARS-CoV-2 focused on the receptor binding domain (RBD) of the Spike (S) protein, whereas the vulnerable epitopes and functional mechanism of non-RBD regions are poorly understood. Here we isolated and characterized monoclonal antibodies (mAbs) derived from convalescent COVID-19 patients. An mAb targeting the N-terminal domain (NTD) of the SARS-CoV-2 S protein, named 4A8, exhibits high neutralization potency against both authentic and pseudotyped SARS-CoV-2, although it does not block the interaction between angiotensin-converting enzyme 2 (ACE2) receptor and S protein. The cryo-EM structure of the SARS-CoV-2 S protein in complex with 4A8 has been determined to an overall resolution of 3.1 Angstrom and local resolution of 3.4 Angstrom for the 4A8-NTD interface, revealing detailed interactions between the NTD and 4A8. Our functional and structural characterizations discover a new vulnerable epitope of the S protein and identify promising neutralizing mAbs as potential clinical therapy for COVID-19.

biochemistry↗

bioRxiv2020

Mixed Culture of Bacterial Cell for Large Scale DNA Storage

DNA emerged as novel material for mass data storage, the serious problem human society is facing. Taking advantage of current synthesis capacity, massive oligo pool demonstrated its high-potential in data storage in test tube. Herein, mixed culture of bacterial cells carrying mass oligo pool that was assembled in a high copy plasmid was presented as a stable material for large scale data storage. Living cells data storage was fabricated by a multiple-steps process, assembly, transformation and mixed culture. The underlying principle was explored by deep bioinformatic analysis. Although homology assembly showed sequence context dependent bias but the massive digital information oligos in mixed culture were constant over multiple successive passaging. In pushing the limitation, over ten thousand distinct oligos, totally 2304 Kbps encoding 445 KB digital data including texts and images, were stored in bacterial cell, the largest archival data storage in living cell reported so far. The mixed culture of living cell data storage opens up a new approach to simply bridge the in vitro and in vivo storage system with combined advantage of both storage capability and economical information propagation.

molecular biology↗

bioRxiv2018

Quantitative Analysis of Interactive Behavior of Mitochondria and Lysosomes Using Structured Illumination Microscopy

Super-resolution optical microscopy has extended the spatial resolution of cell biology from the cellular level to the nanoscale, enabling the observation of the interactive behavior of single mitochondria and lysosomes. Quantitative parametrization of interaction between mitochondria and lysosomes under super-resolution optical microscopy, however, is currently unavailable, which has severely limited our understanding of the molecular machinery underlying mitochondrial functionality. Here, we introduce an M-value to quantitatively investigate mitochondria and lysosome contact (MLC) and mitophagy under structured illumination microscopy. We found that the M-value for an MLC is typically less than 0.4, whereas in mitophagy it ranges from 0.5 to 1.0. This system permits further investigation of the detailed molecular mechanism governing the interactive behavior of mitochondria and lysosomes.

cell biology↗

bioRxiv2018

Using composite phenotypes to reveal heterogeneity and model SpO2 of altitude acclimatization

Altitude acclimatization is the physiological process of the human body adjusting to the decreased availability of oxygen. Since several physiological processes are involved and the relation among them is complicated, analyses of single-traits is insufficient in revealing the complex mechanism of altitude acclimatization. In this study, we examined whether these physiological responses could be studied as composite phenotypes which are represented by a linear combination of physiological traits. We developed a strategy which combines both spectral clustering and PLSPM to define composite phenotypes. We captured 14 composite phenotypes from 28 physiological traits of altitude acclimatization. Using these composite phenotypes, we applied k-means to reveal hidden physiological heterogeneity in altitude acclimatization. Furthermore, we employed linear regression to systematically model oxygen saturation (SpO2) changes in altitude acclimatization and evaluated the model fitness performance. And composite phenotypes based Model 2 has better fitness than single-traits based Model 1 in all measurement indices. Therefore, this new strategy of defining and applying composite phenotypes can be considered as a general strategy of complex traits.

systems biology↗

bioRxiv2018

Robust Reference Powered Association Test of genome-wide association studies

Genome-wide association studies (GWAS) have identified abundant genetic susceptibility loci, although they are far less from meeting the previous expectations due to low statistical power and false positive results. Effective statistical methods are required to further improve the analyses of massive GWAS data. Here we presented a new statistic (Robust Reference Powered Association Test, http://drwang.top/gwas.html) to use large public database as reference to reduce concern of potential population stratification. To evaluate the performance of this statistic for various situations, we simulated multiple sets of sample size and frequencies to compute statistical power. Furthermore, we applied our method to several real datasets (psoriasis genome-wide association datasets and schizophrenia genome-wide association dataset) to evaluate the performance. Careful analyses indicated that our newly developed statistic outperformed several previously developed GWAS applications. Importantly, this statistic is more robust than naive merging method in the presence of small control-reference differentiation, therefore likely to detect more association signals.

genetics↗