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Developmental Biology

Harmonizing Newborn Genetic Screening: A Data-Driven Approach to Gene Selection

More than a decade ago, researchers launched the BabySeq Project, a pilot program to return newborn genomic sequencing results to parents and measure the effects on newborn care. Today, over 30 international initiatives are exploring the expansion of newborn screening using genomic sequencing (NBSeq), but a new study highlights the substantial variability in gene selection among those programs.

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The world of newborn genetic screening has come a long way since the launch of the BabySeq Project over a decade ago. Today, more than 30 international initiatives are exploring the expansion of this critical public health tool using genomic sequencing (NBSeq). However, a recent study by researchers from Mass General Brigham highlights the substantial variability in gene selection among these programs. In a paper published in Genetics in Medicine, the researchers offer a data-driven approach to prioritizing genes for public health consideration.

“It’s essential that we be thoughtful about which genes and conditions are included in genomic newborn screening programs,” said co-senior author Nina Gold, MD, director of Prenatal Medical Genetics and Metabolism at Massachusetts General Hospital (MGH), a founding member of the Mass General Brigham healthcare system. “By leveraging machine learning, we can provide a tool that helps policymakers and clinicians make more informed choices, ultimately improving the impact of genomic screening programs.”

The researchers introduced a machine learning model that brings structure and consistency to the selection of genes for NBSeq programs. This is the first publication from the International Consortium of Newborn Sequencing (ICoNS), founded in 2021 by senior author Robert C. Green, MD, MPH, director of the Genomes2People Research Program at Mass General Brigham, and David Bick, MD, PhD, of Genomics England in the United Kingdom.

The study analyzed 4,390 genes included across 27 NBSeq programs, identifying key factors influencing gene inclusion. While the number of genes analyzed by each program ranged from 134 to 4,299, only 74 genes (1.7%) were consistently included in over 80% of programs. The strongest predictors of gene inclusion were whether the condition is on the U.S. Recommended Uniform Screening Panel, has robust natural history data, and if there is strong evidence of treatment efficacy.

Using these insights, the team developed a machine learning model incorporating 13 predictors, achieving high accuracy in predicting gene selection across programs. The model provides a ranked list of genes that can adapt to new evidence and regional needs, enabling more consistent and informed decision-making in NBSeq initiatives worldwide.

“This research represents a significant step toward harmonizing NBSeq programs and ensuring that gene selection reflects the latest scientific evidence and public health priorities,” said Green.

Behavioral Science

“Rewired for Romance: Scientists Give Gift-Giving Behavior to Singing Fruit Flies”

By flipping a single genetic switch, researchers made one fruit fly species adopt the gift-giving courtship of another, showing how tiny brain rewiring can drive evolutionary change.

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Rewired for Romance: Scientists Give Gift-Giving Behavior to Singing Fruit Flies

In a groundbreaking study published in the journal Science, researchers from Japan have successfully transferred a unique courtship behavior from one species of fruit fly to another. By activating a single gene in insulin-producing neurons, the team made Drosophila melanogaster, a species that typically sings “courtship songs,” perform a gift-giving ritual it had never done before.

The study reveals that the reason for this difference lies in the connection between insulin-producing neurons and the courtship control center in the brain. In gift-giving flies (D. subobscura), these cells are connected, while in singing flies (D. melanogaster), they remain disconnected. This discovery highlights that the evolution of novel behaviors does not necessarily require the emergence of new neurons; instead, small-scale genetic rewiring can lead to behavioral diversification and species differentiation.

The researchers inserted DNA into D. subobscura embryos to create flies with heat-activated proteins in specific brain cells. They used heat to activate groups of these cells and compared the brains of flies that did and did not regurgitate food. The study identified 16-18 insulin-producing neurons that make the male-specific protein FruM, clustered in a part of the brain called the pars intercerebralis.

“Our findings indicate that the evolution of novel behaviors does not necessarily require the emergence of new neurons; instead, small-scale genetic rewiring in a few preexisting neurons can lead to behavioral diversification and, ultimately, contribute to species differentiation,” said Dr. Yusuke Hara, co-lead author from the National Institute of Information and Communications Technology (NICT).

This study demonstrates how scientists can trace complex behaviors like nuptial gift-giving back to their genetic roots to understand how evolution creates entirely new strategies that help species survive and reproduce.

The research was conducted with support from KAKENHI Grant-in-Aid for Scientific Research and has been published in the journal Science on August 14, 2025.

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Agriculture and Food

Breaking New Ground: Scientists Develop Groundbreaking Chromosome Editing Technology

A group of Chinese scientists has created powerful new tools that allow them to edit large chunks of DNA with incredible accuracy—and without leaving any trace. Using a mix of advanced protein design, AI, and clever genetic tweaks, they’ve overcome major limitations in older gene editing methods. These tools can flip, remove, or insert massive pieces of genetic code in both plants and animals. To prove it works, they engineered rice that’s resistant to herbicides by flipping a huge section of its DNA—something that was nearly impossible before.

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The field of genetic engineering has taken a significant leap forward with the development of two new genome editing technologies by a team of Chinese researchers led by Prof. Gao Caixia from the Institute of Genetics and Developmental Biology of the Chinese Academy of Sciences. These innovations, collectively known as Programmable Chromosome Engineering (PCE) systems, have been published in the prestigious journal Cell.

The PCE system is an upgrade to the well-known Cre-Lox technology, which has long been used for precise chromosomal manipulation. However, this older method had three major limitations that hindered its broader application: low recombination efficiency, reversible recombination activity, and the need for a scar (a small DNA fragment) at the editing site.

The research team tackled each of these challenges by developing novel methods to advance the state of this technology. Firstly, they created a high-throughput platform for rapid recombination site modification and proposed an asymmetric Lox site design that reduces reversible recombination activity by over 10-fold.

Secondly, they utilized their recently developed AiCE model – a protein-directed evolution system integrating general inverse folding models with structural and evolutionary constraints – to develop AiCErec. This approach enabled precise optimization of Cre’s multimerization interface, resulting in an engineered variant with a recombination efficiency 3.5 times that of the wild-type Cre.

Lastly, they designed and refined a scarless editing strategy for recombinases by harnessing the high editing efficiency of prime editors to develop Re-pegRNA, a method that uses specifically designed pegRNAs to perform re-prime editing on residual Lox sites, precisely replacing them with the original genomic sequence.

The integration of these three innovations led to the creation of two programmable platforms, PCE and RePCE. These platforms allow flexible programming of insertion positions and orientations for different Lox sites, enabling precise, scarless manipulation of DNA fragments ranging from kilobase to megabase scale in both plant and animal cells.

Key achievements include targeted integration of large DNA fragments up to 18.8 kb, complete replacement of 5-kb DNA sequences, chromosomal inversions spanning 12 Mb, chromosomal deletions of 4 Mb, and whole-chromosome translocations. As a proof of concept, the researchers used this technology to create herbicide-resistant rice germplasm with a 315-kb precise inversion.

This groundbreaking work not only overcomes the historical limitations of the Cre-Lox system but also opens new avenues for precise genome engineering in various organisms, demonstrating its transformative potential for genetic engineering and crop improvement.

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Biochemistry Research

“Unlocking Timekeeping Secrets: Scientists Reveal How Artificial Cells Can Accurately Keep Rhythm”

Scientists at UC Merced have engineered artificial cells that can keep perfect time—mimicking the 24-hour biological clocks found in living organisms. By reconstructing circadian machinery inside tiny vesicles, the researchers showed that even simplified synthetic systems can glow with a daily rhythm—if they have enough of the right proteins.

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A team of researchers from UC Merced has made a groundbreaking discovery by creating tiny artificial cells that can accurately keep time, mimicking the daily rhythms found in living organisms. This achievement sheds light on how biological clocks stay on schedule despite the inherent molecular noise inside cells.

The study, published in Nature Communications, was led by bioengineering Professor Anand Bala Subramaniam and chemistry and biochemistry Professor Andy LiWang. The team’s findings show that artificial cells can glow in a regular 24-hour rhythm for at least four days when loaded with core clock proteins, one of which is tagged with a fluorescent marker.

However, when the number of clock proteins is reduced or the vesicles are made smaller, the rhythmic glow stops. This loss of rhythm follows a reproducible pattern, indicating that clocks become more robust with higher concentrations of clock proteins, allowing thousands of vesicles to keep time reliably – even when protein amounts vary slightly between vesicles.

To explain these findings, the team built a computational model that revealed another component of the natural circadian system – responsible for turning genes on and off – does not play a major role in maintaining individual clocks but is essential for synchronizing clock timing across a population. The researchers also noted that some clock proteins tend to stick to the walls of the vesicles, meaning a high total protein count is necessary to maintain proper function.

“This study shows that we can dissect and understand the core principles of biological timekeeping using simplified, synthetic systems,” Subramaniam said.

The work led by Subramaniam and LiWang advances the methodology for studying biological clocks, according to Mingxu Fang, a microbiology professor at Ohio State University and an expert in circadian clocks. “This new study introduces a method to observe reconstituted clock reactions within size-adjustable vesicles that mimic cellular dimensions,” Fang said. “This powerful tool enables direct testing of how and why organisms with different cell sizes may adopt distinct timing strategies, thereby deepening our understanding of biological timekeeping mechanisms across life forms.”

The study was supported by Subramaniam’s National Science Foundation CAREER award from the Division of Materials Research and by grants from the National Institutes of Health and Army Research Office awarded to LiWang.

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