Tag Archives: genetic

AI is playing an increasingly important role in diagnostic services in healthcare

Researchers at the University of Bonn have trained software to improve our ability to diagnose rare genetic diseases. The program uses a patient’s portrait photograph and analyzes their facial features — such as characteristically shaped brows, nose, or cheeks — to judge how at risk a certain individual is of these ailments.

Dubbed “GestaltMatcher”, the program has successfully diagnosed known diseases in a trial with a very small number of patients.

Automated diagnosis

“The goal is to detect such diseases at an early stage and initiate appropriate therapy as soon as possible,” says Prof. Dr. Peter Krawitz from the Institute for Genomic Statistics and Bioinformatics (IGSB) at the University Hospital Bonn, corresponding author of the paper.

“We are very happy to finally have a phenotype analysis solution for the ultra-rare cases, which can help clinicians solve challenging cases, and researchers to progress rare disease understanding,” says Aviram Bar-Haim of FDNA Inc. in Boston, USA, co-author of the paper, in a press release. “GestaltMatcher helps the physician make an assessment and complements expert opinion.”

The way we perform diagnosis in healthcare will undoubtedly be revolutionized by AI. And, judging from the results of a new study, that revolution is already upon us.

A large number of very rare diseases are rooted in genetic factors. The same hereditary mutations that encode these diseases, however, ale also expressed phenotypically (in the body’s features) in characteristic ways, for example, in the particular shape of the nose, cheeks, or brows. Obviously, these characteristics vary from one disease to another and can be quite subtle, making them a poor diagnosis element — for human doctors, that is.

AI can however pick up on these subtle features and link them to a known disease. The new software analyzes an individual’s facial features from their profile picture, calculates how similar they are to a known set of characteristics, and uses this to estimate the probability that the person in question bears the genes associated with various conditions. The individual’s clinical symptoms and any available genetic data are also factored into the analysis.

The system is a further development of “DeepGestalt”, which the IGSB team trained with other institutions a few years ago. The team worked to improve its ability to learn using a small sample of patients — and the new program is much better in this regard than its predecessor — which is a key feature for software used to diagnose rare diseases, where sample sizes are very limited. Another key improvement is GestaltMatcher’s ability to consider data from patients who have not yet been diagnosed, allowing it to take into account combinations of features that have not yet been described. This, the team explains, allows it to recognize diseases that were previously unknown, and suggest diagnoses based on data available to it.

The program was trained using 17,560 patient photos, most of which came from digital health company FDNA. Around 5,000 of those photographs were contributed by the Institute of Human Genetics at the University of Bonn, along with nine other university sites in Germany and abroad. All in all, these covered 1,115 different rare diseases.

“This wide variation in appearance trained the AI so well that we can now diagnose with relative confidence even with only two patients as our baseline at best, if that’s possible,” Krawitz says.

The data was turned over to the non-profit Association for Genome Diagnostics (AGD), to allow researchers around the world free access to it.

The application is not far off from being available in doctors’ offices in certain countries such as Germany, the team adds. Doctors can simply take portraits of their patients with a smartphone and use the AI to help them in a diagnosis.

Humans started growing cannabis 12,000 years ago — for food, fibers, and probably to get high

A new study traced back the origin of cannabis agriculture to nearly 12,000 years ago in East Asia. During this time cannabis was likely a multipurpose crop — it was only 4,000 years ago that farmers started growing different strains for either fiber or drug production.

Cannabis landraces in Qinghai province, central China. Credit: Guangpeng Ren.

Although it’s largely understudied due to legal reasons, cannabis is one of the first plants to be domesticated by humans. Archaeological studies have found traces of cannabis in various different cultures across the centuries, but when and where exactly was cannabis domesticated was still unclear.

Many botanists believed the plant emerged in central Asia, but a new study shows that east Asia (including parts of China) is the origin of domesticated cannabis.

A research team was led by Luca Fumagalli of the University of Lausanne and involved scientists from Britain, China, India, Pakistan, Qatar, and Switzerland. The researchers compared and analyzed 110 whole genomes of different plants, ranging from wild-growing feral plants and landraces to historical cultivars and modern hybrids.

They concluded that the ancestral domestication of cannabis plants occurred some 12,000 years ago, during a period called the Neolithic, and that the plants likely had multiple uses.

“We show that cannabis sativa was first domesticated in early Neolithic times in East Asia and that all current hemp and drug cultivars diverged from an ancestral gene pool currently represented by feral plants and landraces in China,” the study reads.

“Our genomic dating suggests that early domesticated ancestors of hemp and drug types diverged from Basal cannabis [around 12,000 years ago] indicating that the species had already been domesticated by early Neolithic times”, the study adds. The results go against a popular theory regarding the plant’s origin, the researchers add.

“Contrary to a widely-accepted view, which associates cannabis with a Central Asian center of crop domestication, our results are consistent with a single domestication origin of cannabis sativa in East Asia, in line with early archaeological evidence.”

When a study can land you in jail

Cannabis grown for drugs. Image credits: Esteban Lopez.

It’s hard to study cannabis, regardless of what your reasons are. You can’t just go around picking or buying plants because the odds are that’ll get you in trouble. To make matters even more difficult, if you want to see where a domesticated plant originated from, you have to collect samples from different parts of the world — which is even more likely to get you in trouble.

So for decades, researchers looked at indirect evidence. Most cannabis strains appear to be from Central Asia, and several cultures of that region have used cannabis for thousands of years, so that seems like a likely place of origin. It’s a good guess, but not exactly true.

Cannabis grows pretty much everywhere — that’s why it’s called “weed” — and just because people in Central Asia were quick to adopt the plant doesn’t necessarily mean they were the first ones to grow it.

After crossing legal and logistic hurdles, Fumagalli was able to gather around 80 different types of cannabis plants, either cultivated by farmers or growing in the wild. They also included 30 previously sequenced genomes in the analysis.

With this, they found that the likely ancestor of modern cannabis (the initial wild plant that was domesticated) is likely extinct. However, its closest relatives survive in parts of northwestern China. This fits very well with existing archaeological evidence, which shows evidence of hemp cord markings some 12,000 years ago. In particular, it seems to fit with a 2016 study by other scientists that said that the earliest cannabis records were mostly from China and Japan.

The early domestication of cannabis in the Neolithic could be a big deal. Cannabis isn’t exactly a food crop. You can indeed use it to get oil, and the seeds can be consumed but its main use is for fibers and for intoxication. Usually, when archaeologists look at a population domesticating a crop, they naturally think of food as a priority — but this would suggest that Neolithic folk also had, uhm, other priorities. Or simply, cannabis was a multi-purpose crop.

Diversifying crops

The team also identified the genetic changes that farmers brought over the centuries through selective breeding. They found that some 4,000 years ago, farmers started to focus on either plants that would produce fibers, or on those better suited for producing drugs.

For instance, hemp strains bred for fiber production have mutations that inhibit branching, which makes them grow taller and produce more fibers. Meanwhile, strains bred for drug production, have mutations that encourage branching and reduce vertical growth. This results in shorter plants that produce more flowers. In addition, plants grown for drug productions also have mutations that boost the production of tetrahydrocannabinol (THC).

For millennia, hemp (the cannabis grown for fibers) has been an important crop. Clothes, ropes, and various other products used hemp fibers, but the emergence of modern metalworking and modern synthetic fibers (such as nylon) led to its downfall, and the once-popular plant became all but forgotten. Until recently.

A modern cannabis greenhouse. Image credits: Richard T.

Recently, we’ve seen a resurgence in the interest in cannabis, for sustainable fiber production as well as medicinal and recreational purposes. With more and more countries decriminalizing the possession and growth of cannabis, the plant may be making a comeback — and for researchers looking to study its origin, that’s great news.

While this study offers an unprecedented view into the evolutionary history of cannabis, it’s still a relatively small sample size. Finding wild samples is hard — and feral samples you find today aren’t really wild, they’re just grown varieties that escaped and are now feral. Furthermore, even gaining access to cultivars can be difficult.

Maybe, as society becomes more inclined to consider cannabis, researchers can gain access to more resources about it as well. By studying its genomic history, scientists can also provide valuable insights into the desired functional properties of plants, helping growers develop better varieties both for medicine and for other uses.

The study has been published in Science Advances.

For all the damage they cause, viruses also help push evolution

“What we learn from our study is that, in general, viruses have major roles in driving evolution,” one researcher explained. “In the long-term, viruses have positive impacts to our genome and shape evolution.”

While the general principles of evolution are fairly straightforward, the details behind the process is immensely complex. What if someone told you, for instance, that viruses help fine-tune evolution; that these dreaded organisms that aren’t really organisms can help push the survival of a species? As weird as it sounds, that’s one takeaway from the two studies published by the Cincinnati Children’s Perinatal Institute and at Azabu University in Japan.

The scientists looked at lab mice and human sex cells, or to be more precise, at the germline cells — the cells that form the egg, sperm, and the fertilized egg that pass on their genetic material to the progeny (offspring).

Specifically, they looked at the set of all RNA of these sex cells, something called transcriptomes.

These transcriptomes contained either the male or the female half of chromosomes passed on as genetic materials when species mate. In other words, they define the unique character of sperm and egg as they pass on genetic information to the next generations.

The two published papers look at some of the processes behind these transcriptomes. Satoshi Namekawa, principal investigator on both papers, combined biological testing of mouse models and human germline cells with computational biology to see how genes are produced and reorganized following sexual reproduction. He found that a key element in this process is something called super-enhancers.

“One paper, Maezawa and Sakashita et al., explores super-enhancers, which are robust and evolutionally conserved gene regulatory elements in the genome. They fuel a tightly regulated burst of essential germline genes as sperm start to form,” Namekawa said.

Super-enhancers are regulated by two molecules that act as gene control switches. This is where the second study comes in, Namekawa explains.

“The second study, Sakashita et al., involves endogenous retroviruses that act as another type of enhancer – gene regulatory elements in the genome – to drive expression of newly evolved genes. This helps fine tune species-specific transcriptomes in mammals like humans, mice, and so on.

Endogenous retroviruses are normal components of the human genome and account for around 8% of our DNA — in fact, they account for over 5% of many mammals’ DNA. Also referred to as “jumping genes”, these retroviruses have traditionally been considered threats because they can disrupt some genes. However, over the past few decades, researchers have found that these viruses can actually act as regulatory elements for our genome.

This is exactly what Namekawa and colleagues have found. Endogenous retroviruses can help fine-tune transcriptomes, essentially helping a species’ evolution and diversity.

Super-enhancer switching drives a burst in gene expression at the mitosis-to-meiosis transition, Nature Structural & Molecular BiologyDOI: 10.1038/s41594-020-0488-3 

New study furthers our understanding of how genetics influence heavy drinking

A new study comes to flesh out our understanding of the genetic basis for problematic drinking.

Image via Pixabay.

Previously, we knew of 13 gene variants associated with heavy drinking. Now, this study expands our knowledge to an impressive 29 different gene variants linked to problematic alcohol use. One limitation of the study is that, despite its relatively large sample of 435,000 people, all of them were of European descent.

Bottoms up

“The new data triple the number of known genetic risk loci associated with problematic alcohol use,” said Joel Gelernter at Yale University School of Medicine, the Foundations Fund Professor of Psychiatry and a professor of genetics and neuroscience.

Foundations Fund Professor of Psychiatry and professor of genetics and of neuroscience, who is the senior author of the multi-institutional study.

The study looked at genome-wide records of people of European ancestry contained in four separate biobanks and datasets. The team identified individuals who met criteria for problematic drinking, including alcohol use disorder and alcohol use with medical consequences and then looked for genetic variants they all shared.

They located 19 previously-unknown genes that represent risk factors for such behavior, alongside 10 previously-identified genes.

Furthermore, they looked at genetic risk factors for several psychiatric disorders including anxiety disorder and depression in the genomes. During the study, this step allowed them to analyze the genetic links between such disorders and heavy drinking. Major depressive disorder showed the greatest correlation to problematic drinking; risk-taking behavior, insomnia were also positively correlated with such behavior.

The genes identified in this study are particularly stable from a hereditary point of view in the brain (they’re more stable across generations) and in “evolutionarily conserved regulatory regions of the genome”, which suggests that they perform important functions in our metabolism. Exactly what these functions remain to be determined.

“This gives us ways to understand causal relations between problematic alcohol use traits such as psychiatric states, risk-taking behavior, and cognitive performance,” said Yale’s Hang Zhou, associate research scientist in psychiatry and lead author of the study. “With these results, we are also in a better position to evaluate individual-level risk for problematic alcohol use,” Gelernter said.

Heavy drinking is associated with adverse medical and social outcomes, so understanding which people are at risk for such behavior could help us better protect them.

The paper “Genome-wide meta-analysis of problematic alcohol use in 435,563 individuals yields insights into biology and relationships with other traits” has been published in the journal Nature Neuroscience.