One of the ultimate goals of biological research is to understand the multiscale organization of the human cell and its relationship to biological function and human disease. As much of cell structure remains uncharted, there has been long-standing interest in developing strategies to map this architecture systematically.
In a new study published in Nature titled, “Multimodal cell maps as a foundation for structural and functional genomics,” researchers from the University of California (UC), San Diego, have constructed a global map of subcellular architecture for over 5,000 proteins in U2OS osteosarcoma cells, which are associated with pediatric bone tumors. The work was a collaboration with researchers at Stanford University, Harvard Medical School, and the University of British Columbia.
The study presented a large-scale multimodal cell mapping pipeline, which leveraged high-resolution microscope imaging and biophysical interactions of proteins for broader applications in structural and functional genomics. Additionally, GPT-4, a large language model similar to ChatGPT, was used to draw upon the huge knowledge base of scientific literature to inform functional annotation of the human cell map.
“ We know each of the proteins that exist in our cells, but how they fit together to then carry out the function of a cell still remains largely unknown across cell types,” said Leah Schaffer, PhD, lead author of the paper and a postdoctoral research scholar at UC San Diego School of Medicine.
The results revealed functions for 975 proteins whose role was previously unknown, including C18orf21, which was shown to be involved in RNA processing, and the DPP9 protein, which was implicated in interferon signaling, an important function while fighting infection.
Additionally, the study identified 21 assemblies frequently mutated in childhood cancer. Within these groups, 102 mutated proteins were found to be strongly linked to cancer development.
“We need to stop looking at the level of individual mutations, which are very rare, sporadic, and almost never recur in the same way twice, and start looking at the common machinery inside of cells that is disrupted or hijacked by these mutations,” said Trey Ideker, PhD, co-corresponding author and professor of medicine at UC San Diego.
According to Emma Lundberg, PhD, another co-corresponding author of the paper and associate professor of bioengineering and pathology at Stanford University, scientists have historically been biased by the notion that “one gene codes for one protein that has one function.” However, there’s an increasing number of multifunctional proteins that remain underestimated.
“This study demonstrates the importance of multimodal data integration to reveal these multifunctional properties,” said Lundberg.
Schaffer describes browsing the U2OS cell map as similar to navigating an online geographical map. “You’re able to really explore, zoom in, and see what proteins are part of these different communities, and then see where those communities are located,” she said. According to the team, increasing the resolution of the map remains an ongoing goal.
Taken together, the researchers state that the U2OS cell atlas will not only facilitate an understanding of childhood cancers, but also provide a blueprint for scientists to map other cell types, use artificial intelligence tools to uncover the function of poorly understood proteins, and decipher the mechanisms behind a wide variety of disease processes.
The post Human Cell Maps Uncover Insights in Pediatric Bone Cancer appeared first on GEN - Genetic Engineering and Biotechnology News.
In a new study published in Nature titled, “Multimodal cell maps as a foundation for structural and functional genomics,” researchers from the University of California (UC), San Diego, have constructed a global map of subcellular architecture for over 5,000 proteins in U2OS osteosarcoma cells, which are associated with pediatric bone tumors. The work was a collaboration with researchers at Stanford University, Harvard Medical School, and the University of British Columbia.
The study presented a large-scale multimodal cell mapping pipeline, which leveraged high-resolution microscope imaging and biophysical interactions of proteins for broader applications in structural and functional genomics. Additionally, GPT-4, a large language model similar to ChatGPT, was used to draw upon the huge knowledge base of scientific literature to inform functional annotation of the human cell map.
“ We know each of the proteins that exist in our cells, but how they fit together to then carry out the function of a cell still remains largely unknown across cell types,” said Leah Schaffer, PhD, lead author of the paper and a postdoctoral research scholar at UC San Diego School of Medicine.
The results revealed functions for 975 proteins whose role was previously unknown, including C18orf21, which was shown to be involved in RNA processing, and the DPP9 protein, which was implicated in interferon signaling, an important function while fighting infection.
Additionally, the study identified 21 assemblies frequently mutated in childhood cancer. Within these groups, 102 mutated proteins were found to be strongly linked to cancer development.
“We need to stop looking at the level of individual mutations, which are very rare, sporadic, and almost never recur in the same way twice, and start looking at the common machinery inside of cells that is disrupted or hijacked by these mutations,” said Trey Ideker, PhD, co-corresponding author and professor of medicine at UC San Diego.
According to Emma Lundberg, PhD, another co-corresponding author of the paper and associate professor of bioengineering and pathology at Stanford University, scientists have historically been biased by the notion that “one gene codes for one protein that has one function.” However, there’s an increasing number of multifunctional proteins that remain underestimated.
“This study demonstrates the importance of multimodal data integration to reveal these multifunctional properties,” said Lundberg.
Schaffer describes browsing the U2OS cell map as similar to navigating an online geographical map. “You’re able to really explore, zoom in, and see what proteins are part of these different communities, and then see where those communities are located,” she said. According to the team, increasing the resolution of the map remains an ongoing goal.
Taken together, the researchers state that the U2OS cell atlas will not only facilitate an understanding of childhood cancers, but also provide a blueprint for scientists to map other cell types, use artificial intelligence tools to uncover the function of poorly understood proteins, and decipher the mechanisms behind a wide variety of disease processes.
The post Human Cell Maps Uncover Insights in Pediatric Bone Cancer appeared first on GEN - Genetic Engineering and Biotechnology News.