CHOP and NJIT Researchers Develop New Tool for Studying Multiple Characteristics of a Single Cell

Philadelphia, December 21, 2022 – Researchers from Children’s Hospital of Philadelphia (CHOP) and New Jersey Institute of Technology (NJIT) developed new software that integrates a variety of information from a single cell, allowing researchers to see how one change in a cell can lead to several others and providing important clues for pinpointing the exact causes of genetic-based diseases.

The findings were published by Nature Communications.

Single-cell sequencing allows researchers to look at specific aspects of a cell to determine how it interacts with its microenvironment. This is particularly relevant in cancer research since it can be used to determine the effects of a mutation that may only affect a small portion of cells. At the single-cell level, researchers can study gene expression as well as messenger RNA, proteins and even organelles within the cells in much greater detail and resolution than before.

However, because each of the characteristics of a single cell has been studied individually, their connections with one another – for example, how a genetic variant might directly impact messenger RNA, protein synthesis or epigenetics – may not be apparent, even when comparing data generated from the same cell.

To address this statistical and computational dilemma, the researchers developed an automated single-cell multimodal sequencing clustering software tool to profile what is happening within the cell across multiple biological processes simultaneously and better characterize relationships between changes in a cell.

“With this tool, we can better understand a single cell as an entity and not just as a fragmented unit,” said Hakon Hakonarson, MD, PhD, director of the Center for Applied Genomics at CHOP and a senior author of the study. “This is a significant advancement and allows us to integrate and put all of this information into biological perspective, which is particularly important when considering information on different diseases.”

The software, referred to as single-cell multimodal deep clustering (scMDC), uses machine learning to analyze data about different characteristics of a single cell. The researchers conducted extensive simulation and real-data experiments and found that scMDC outperformed existing single cell single-modal and multimodal clustering methods on single-cell multimodal data sets. It also utilizes linear scalability, meaning that more data sources provided to the scMDC yield better results.

This study was supported by National Institutes of Health grant R15HG012087 and the National Center for Advancing Translational Sciences under grant number UL1TR003017. The computing resource was partially provided by Extreme Science and Engineering Discovery Environment (XSEDE) through allocation CIE160021 and CIE17003, supported by National Science Foundation Grant ACI-1548562.

Lin et al, “Clustering of single-cell multi-omics data with a multimodal deep learning method.” Nat Comm. Online December 13, 2022. DOI: 10.1038/s41467-022-35031-9.

About Children’s Hospital of Philadelphia: A non-profit, charitable organization, Children’s Hospital of Philadelphia was founded in 1855 as the nation’s first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals, and pioneering major research initiatives, the 595-bed hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country. The institution has a well-established history of providing advanced pediatric care close to home through its CHOP Care Network, which includes more than 50 primary care practices, specialty care and surgical centers, urgent care centers, and community hospital alliances throughout Pennsylvania and New Jersey, as well as a new inpatient hospital with a dedicated pediatric emergency department in King of Prussia. In addition, its unique family-centered care and public service programs have brought Children’s Hospital of Philadelphia recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu. 

About New Jersey Institute of Technology: One of only 35 polytechnic universities in the United States, New Jersey Institute of Technology (NJIT) is an R1 (most elite) Carnegie Classification research university that offers more than 125 undergraduate and graduate degree programs and spurs economic growth while preparing students to become leaders in the technology-dependent economy of the 21st century. NJIT is a catalyst for applied research and innovation that improves lives and fosters economic growth. Ranked No. 14 in the nation on Money’s Best Colleges list, NJIT also stands among the top 100 colleges and universities nationally for the mid-career earnings of its graduates, according to PayScale.com. NJIT is ranked No. 33 nationally by The Princeton Review as a Best Value College and is rated among the top 50 public national universities and top 100 overall by U.S. News & World Report.