Professor Nikolaus Rajewsky is a visionary: He wants to understand exactly what happens in human cells during disease progression, with the goal of being able to recognize and treat the very first cellular changes. "This requires us not only to decipher the activity of the genome in individual cells, but also to track it spatially within an organ," explains the scientific director of the Berlin Institute for Medical Systems Biology (BIMSB) at the Max Delbrck Center for Molecular Medicine (MDC) in Berlin. For example, the spatial arrangement of immune cells in cancer ("microenvironment") is extremely important in order to diagnose the disease accurately and select the optimal therapy. "In general, we lack a systematic approach to molecularly capture and understand the (patho-)physiology of a tissue."
Maps for very different tissue typesRajewsky has now taken a big step towards his goal with a major new study that has been published in the scientific journal Nature. Together with Professor Nir Friedman from the Hebrew University of Jerusalem, Dr. Mor Nitzan from Harvard University in Cambridge, USA, and Dr. Nikos Karaiskos, a project leader from his own research group on "Systems Biology of Gene Regulatory Elements", the scientists have succeeded in using a special algorithm to create a spatial map of gene expression for individual cells in very different tissue types: in the liver and intestinal epithelium of mammals, as well as in embryos of fruit flies and zebrafish, in parts of the cerebellum, and in the kidney. "Sometimes purely theoretical science is enough to publish in a high-ranking science journal - I think this will happen even more frequently in the future. We need to invest a lot more in machine learning and artificial intelligence," says Nikolaus Rajewsky.
"Using these computer-generated maps, we are now able to precisely track whether a specific gene is active or not in the cells of a tissue part," explains Karaiskos, a theoretical physicist and bioinformatician who developed the algorithm together with Mor Nitzan. "This would not have been possible in this form without our model, which we have named 'novoSpaRc.'"
Spatial information was previously lost
It is only in recent years that researchers have been able to determine - on a large scale and with high precision - which information individual cells in an organ or tissue are retrieving from the genome at any given time. This was thanks to new sequencing methods, for example multiplex RNA sequencing, which enables a large number of RNA molecules to be analyzed simultaneously. RNA is produced in the cell when genes become active and proteins are formed from their blueprints. Rajewsky recognized the potential of single-cell sequencing early on, and established it in his laboratory.
"But for this technology to work, the tissue under investigation must first be broken down into individual cells," explains Rajewsky. This process causes valuable information to be lost: for example, the original location in the tissue of the particular cell whose gene activity has been genetically decoded. Rajewsky and Friedmann were therefore looking for a way to use data from single-cell sequencing to develop a mathematical model that could calculate the spatial pattern of gene expression for the entire genome - even in complex tissues.
The teams led by Rajewsky and Dr. Robert Zinzen, who also works at BIMSB, already achieved a first breakthrough two years ago. In the scientific journal Science, they presented a virtual model of a fruit fly embryo. It showed which genes were active in which cells in a spatial resolution that had never before been achieved. This gene mapping was made possible with the help of 84 marker genes: in situ experiments had determined where in the egg-shaped embryo these genes were active at a certain point in time. The researchers confirmed their model worked with further complex in situexperiments on living fruit fly embryos.
A puzzle with tens of thousands of pieces and colors
"In this model, however, we reconstructed the location of each cell individually," said Karaiskos. He was one of the first authors of both the "Science" study and the current "Nature" study. "This was possible because we had to deal with a considerably smaller number of cells and genes. This time, we wanted to know whether we can reconstruct complex tissue when we have hardly any or no previous information. Can we learn a principle about how gene expression is organized and regulated in complex tissues?" The basic assumption for the algorithm was that when cells are neighbors, their gene activity is more or less alike. They retrieve more similar information from their genome than cells that are further apart.
To test this hypothesis, the researchers used existing data. For liver, kidney and intestinal epithelium there was no additional information. The group had been able to collect only a few marker genes by using reconstructed tissue samples. In one case, there were only two marker genes available.
"It was like putting together a massive puzzle with a huge number of different colors - perhaps 10,000 or so," explains Karaiskos, trying to describe the difficult task he was faced with when calculating the model. "If the puzzle is solved correctly, all these colors result in a specific shape or pattern." Each piece of the puzzle represents a single cell of the tissue under investigation, and each color an active gene that was read by an RNA molecule.
The method works regardless of sequencing technique"We now have a method that enables us to create a virtual model of the tissue under investigation on the basis of the data gained from single-cell sequencing in the computer - regardless of which sequencing method was used," says Karaiskos. "Existing information on the spatial location of individual cells can be fed into the model, thus further refining it." With the help of novoSpaRc, it is then possible to determine for each known gene where in the tissue the genetic material is active and being translated into a protein.
Now, Karaiskos and his colleagues at BIMSB are also focusing on using the model to trace back over and even predict certain developmental processes in tissues or entire organisms. However, the scientist admits there may be some specific tissues that are incompatible with the novoSpaRc algorithm. But this could be a welcome challenge, he says: A chance to try his hand at a new puzzle!
Reference: Nitzan, Karaiskos, Friedman and Nikolaus Rajewsky. 2019. Gene expression cartography. DOI: https://doi.org/10.1038/s41586-019-1773-3.
This article has been republished from the following materials. Note: material may have been edited for length and content. For further information, please contact the cited source.
Go here to see the original:
Calculating the Spatial Pattern of Gene Expression for the Entire Genome - Technology Networks
- Exercise promotes a molecular profile in muscle: Research - January 21st, 2023
- Molecular Diagnostics Laboratory < Laboratory Medicine - January 4th, 2023
- Molecular cloning - Wikipedia - December 18th, 2022
- Trends in Molecular Medicine | Journal - ScienceDirect - December 10th, 2022
- Researchers from Insilico Medicine, University of Copenhagen, and University of Chicago unravel molecular secrets hidden in premature aging diseases... - December 2nd, 2022
- Nuclear Medicine and Molecular Imaging Week: October 2-8, 2022 - October 29th, 2022
- Biochemistry & Molecular Biology | Medicine - October 29th, 2022
- Cellular and Molecular Medicine | Faculty of Medicine - October 21st, 2022
- Molecular Diagnostics > Fact Sheets > Yale Medicine - October 21st, 2022
- Expert Reviews in Molecular Medicine | Cambridge Core - October 13th, 2022
- UT Southwestern ranked top health care institution globally for published research by Nature Index - UT Southwestern - October 13th, 2022
- Common Antibiotics Are Losing Their Potency. Researchers Pinpoint Mechanism to Restore It. - NYU Langone Health - October 13th, 2022
- expert reaction to study looking at integrating human stem cell-derived brain-like tissue in the brains of newborn rats - Science Media Centre - October 13th, 2022
- HTG Provides Update on Third Quarter Progress Toward Its Transcriptome-Informed Approach to Drug Discovery - Yahoo Finance - October 13th, 2022
- UVA Discovers Key Driver of High Blood Pressure - UVA Health Newsroom - October 13th, 2022
- Postdoctoral Fellow in Lung Cancer Genomics job with NORWEGIAN UNIVERSITY OF SCIENCE & TECHNOLOGY - NTNU | 311727 - Times Higher Education - October 13th, 2022
- Common cold may increase the risk of long Covid - Earth.com - October 13th, 2022
- Caris' Precision Oncology Alliance Welcomes The Cancer Institute at The University of Tennessee Medical Center - PR Newswire - October 13th, 2022
- Merus Announces Publication of Abstract on MCLA-129 at the 34th EORTC/NCI/AACR (ENA) Symposium on Molecular Targets and Cancer Therapeutics - Yahoo... - October 13th, 2022
- Molecular Test Could Improve Early Detection of Pancreatic Cancer - Technology Networks - October 13th, 2022
- UTSW researchers identify key player in cellular response to stress - EurekAlert - October 4th, 2022
- New Antibody Demonstrates Therapeutic Benefits Against Alzheimers - SciTechDaily - October 4th, 2022
- Mount Sinai study uncovers mechanisms of reactive oxygen species in stem cell function and inflammation prevention - EurekAlert - October 4th, 2022
- NovoPath Pushes the Limits of Laboratory Information Systems with Integrated Workflows for Genetic and Molecular Testing - PR Newswire - October 4th, 2022
- Postdoctoral Fellow in Bioinformatics job with NORWEGIAN UNIVERSITY OF SCIENCE & TECHNOLOGY - NTNU | 311073 - Times Higher Education - October 4th, 2022
- Breast Cancer Awareness | Nick Jacobs | An unlikely partnership: The United States Army Space and Missile Defense Command and the Joyce Murtha Breast... - October 4th, 2022
- Tackling resistance to HIF2 drugs with an RNA-based therapy - UT Southwestern - October 4th, 2022
- OncoNano Medicine Announces Positive Phase 2 Data for Pegsitacianine as an adjunct to Cytoreductive Surgery of Peritoneal Carcinomatosis - Business... - October 4th, 2022
- SIMATS organizes Induction Ceremony - Afternoonnews - Afternoon News - October 4th, 2022
- ExPath Grad Student Madeline Mayday Awarded Grant from the NIDDK Cooperative Centers of Excellence in Hematology - Yale School of Medicine - September 25th, 2022
- Blood Cancer Discovery Publication Further Validates Exscientia's AI Precision Medicine Platform for Improving Patient Outcomes - Business Wire - September 25th, 2022
- New Startups Built From UC Davis Innovations Drive Solutions in Food, Health and Agriculture - University of California, Davis - September 25th, 2022
- Scientists Discover New Cancer Treatment - The Morning News - September 25th, 2022
- Rewriting the Textbook for Precision Medicine - Technology Networks - September 25th, 2022
- Biden says 'The pandemic is over,' but health experts disagree - Chief Healthcare Executive - September 25th, 2022
- Discovery Illuminates How Parkinson's Disease Spreads in The Brain - Weill Cornell Medicine Newsroom - September 25th, 2022
- AI Used to Determine Cause of Alzheimer's and Related Disorders - Inside Precision Medicine - September 25th, 2022
- Looking Ahead in the Treatment of Breast Cancer - Targeted Oncology - September 25th, 2022
- Researchers identify potential biomarker to distinguish two aggressive types of brain tumors in children - EurekAlert - September 25th, 2022
- New study reveals breakthrough infections increase immunity to COVID-19 - OHSU News - September 25th, 2022
- Coronavirus Today: Who's dying of COVID-19 now? - Los Angeles Times - September 25th, 2022
- Hoag Named Radiopharmaceutical Therapy Center of Excellence, Publishes Results of Breast and Prostate Cancer Trials - PR Newswire - September 8th, 2022
- Orbital Therapeutics Launches to Advance New Frontiers of Science with the Next Generation of Innovative RNA Medicines - Yahoo Finance - September 8th, 2022
- Scientists urged the Biden administration to launch an Operation Warp Speed to develop inhaled COVID vaccines. China beat the U.S. to the punch -... - September 8th, 2022
- Foundation Medicine to Share 14 Abstracts at the 2022 European Society for Medical Oncology (ESMO) Congress Demonstrating the Power of Genomic... - September 8th, 2022
- Monte Rosa Therapeutics Announces FDA Clearance of Investigational New Drug Application for MRT-2359, a GSPT1-directed Molecular Glue Degrader Phase... - September 8th, 2022
- Biden administration says the once-a-year shot phase of the COVID-19 pandemic has arrived - The Boston Globe - September 8th, 2022
- ICCBS welcomes students of MPhil and PhD Programs 2022 - The Academia Mag - September 8th, 2022
- Exciting PhD positions at the European Molecular Biology Laboratory (EMBL) job with EUROPEAN MOLECULAR BIOLOGY LABORATORY (EMBL) | 308114 - Times... - September 8th, 2022
- Congratulations to our NRF award winners | UCT News - University of Cape Town News - September 8th, 2022
- Patients with some forms of aggressive esophageal cancers may benefit from treatment targeting how cells self-regulate - EurekAlert - September 8th, 2022
- Molecular Medicine (M.Sc.) - Georg-August-Universitt Gttingen - August 30th, 2022
- Gradalis Announces Publication in Nature Communications Medicine Identifying Survival Predicting Biomarker in Patients with Ovarian Cancer Treated... - August 30th, 2022
- Feinstein Institutes Get $3M From Lupus Research Alliance to Study Remission and Future Therapies - Business Wire - August 30th, 2022
- Unlocking the Power of Precision Medicine the Rheumatology Example - Technology Networks - August 30th, 2022
- When to trust your covid test results and when to question them | Mint - Mint - August 30th, 2022
- Molecular Diagnostics Market Report 2022-2030: Increasing Adoption of Point-Of-Care (Poc) Testing and the Development of Novel Assays Presents... - August 30th, 2022
- Advancing Precision Oncology, Ochsner Health First to Fully Integrate with Tempus and Epic's Genomics Module - Newswise - August 30th, 2022
- Tiny, Touch-Based Sensor Could Help Patients Stay on Top of Their Medications - SciTechDaily - August 30th, 2022
- Stellar Scholars Join CLAS Faculty - UConn Today - University of Connecticut - August 30th, 2022
- COVID-19 gave new urgency to the science of restoring smell - Science News Magazine - August 30th, 2022
- Dr. Sun lab wins R01 from National Institutes of Health to study liver proteins - Wayne State University - August 22nd, 2022
- Pasithea Therapeutics to Present Results of Tolerizing Vaccine Program at Prestigious International Immunotherapy Conference - GlobeNewswire - August 22nd, 2022
- New Study Identifies How A Group Of Genes Are Linked To Behavioral Conditions - Forbes - August 22nd, 2022
- New gene variant that protects against coronary heart disease uncovered - EurekAlert - August 22nd, 2022
- How a Japanese Herbal Medicine Protects the Gut Against Inflammatory Bowel Disease - Neuroscience News - August 22nd, 2022
- Insilico Medicine presents on AI for drug discovery at 9th Annual Aging Research and Drug Discovery Conference - EurekAlert - August 22nd, 2022
- Why polio is back on the radar of Canadian health officials - Brighter World - August 22nd, 2022
- Angela DeMichele, MD, MSCE, Assesses the Value of I-SPY2 for Neoadjuvant Treatment of Early Breast Cancer - Cancer Network - August 22nd, 2022
- Exciting PhD positions at the European Molecular Biology Laboratory (EMBL) job with EUROPEAN MOLECULAR BIOLOGY LABORATORY (EMBL) | 304753 - Times... - August 22nd, 2022
- Sensor could help patients stay on top of their meds - EurekAlert - August 22nd, 2022
- Trivitron Healthcare launches CoE in metabolomics, genomics, newborn screening and molecular diagnostics - Express Healthcare - August 22nd, 2022
- Research Trends of Moxibustion Therapy for Pain Treatment Over the Pas | JPR - Dove Medical Press - August 22nd, 2022
- Edited Transcript of EXAI.OQ earnings conference call or presentation 18-Aug-22 12:30pm GMT - Yahoo Finance - August 22nd, 2022
- Roche launches COVID-19 test that detects and differentiates the emerging variant of interest BA.2.75 - PR Newswire - August 22nd, 2022
- Will Omicron BA.5 Be the Last of the COVID Variants? - The Epoch Times - August 22nd, 2022
- Many Paths to Failure | Harvard Medical School - Harvard Medical School - August 5th, 2022
- Mitochondrial DNA Mutations Linked to Heart Disease Risk - University of California San Diego - August 5th, 2022
- UC Davis Sets a New Record, Surpasses $1 Billion in Research Funding - University of California, Davis - August 5th, 2022
- A first update on mapping the human genetic architecture of COVID-19 - Nature.com - August 5th, 2022