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DeepMind and Alphabet at Calico introduced a neural network architecture called Enformer that greatly improved the accuracy of predicting gene expression based on DNA sequence.

In the paper Effective gene expression prediction from sequence by integrating long-range interactions published in Nature Methods, DeepMind suggested that Enformer is more accurate than Basenji.

The basic building blocks of gene expression have typically been convolutional neural networks. They have, however, been limited in their ability and effectiveness to model due to the effects of distal enhancers on gene expression.

So Deepmind depends on Basenji2, built on TensorFlow, which offers a variety of benefits, including distributed computing, a large and adaptive developer community, and is designed to predict quantitative signals using regression loss functions, rather than binary signals using classification loss functions.

The best part of Basenji is that it could predict the regulatory activity of 40,000 base pair DNA sequences at a time.

Enformer, on the other hand, relies on a technique common to natural language processing from Google called Transformers to take into account self-attention mechanisms that would be able to integrate much more DNA context. As Transformers can read long text passages, DeepMind modified them to read DNA sequences of vastly extended length.

Enformer outperformed the best team on the critical assessment of genome interpretation challenge (CAGI5) for noncoding variant interpretation despite no additional training. Furthermore, Enformer learned to predict promoter-enhancer interactions directly from DNA sequences, competing with methods that took direct experimental data as input.

In the case of training, DeepMind used Sonnet to construct neural networks used for many different purposes. It is defined in enformer.py.

DeepMind pre-computed variant effect scores for all frequent variants (MAF>0.5%, in any population) and stored them in HDF5 files per chromosome for the HG19 reference genome under the 1000 genomes project. Additionally, they provide the top 20 principal components of variant-effect scores per chromosome in a tabix-indexed TSV file (HG19 reference genome). These files have the following columns:

Hopefully, these advances will enable better mapping of growing human disease associations to cell-type-specific gene regulatory mechanisms and provide a framework to understand how cis-regulatory evolution works.

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The Enformer vs the Basenji - The AI Algorithms for gene expression predictions - Analytics India Magazine

When the coronavirus pandemic and its subsequent lockdowns first took over the world nearly two years ago it birthed a multitude of oddities, from awkward enforced weekly Zoom quizzes to gifting health workers non-refundable clapping from our front doorsteps. But while the majority of us became sourdough bread specialists, the most deranged reactions came from celebrities, who took to social media to accidentally advocate for eugenics (Vanessa Hudgens) or cry about a delay to their album release (Dua Lipa). But the prize for the most cringe post of the early pandemic era belongs to, of course, the Gal Gadot-led Imagine video.

Spearheaded by the Wonder Woman actress and Bridesmaids Kristen Wiig and featuring a smorgasbord of stars Jamie Dornan, Natalie Portman, Ashley Benson, Kaia Gerber, Cara Delevingne, Zo Kravitz those benevolent millionaires each hoped to cheer the world with an awkwardly-sung line of the John Lennon song from the comfort of their Selling Sunset-style homes. Naturally, the video was slammed across social media; now, almost 2 years later, Gal has finally admitted that the video might have been a mistake.

Speaking to InStyle, after recently parodying the video during her acceptance speech at the Elle Women in Hollywood Awards, Gal said: I was calling Kristen [Wiig] and I was like, "Listen, I want to do this thing." The pandemic was in Europe and Israel before it came [to the US] in the same way. I was seeing where everything was headed. But [the video] was premature. It wasn't the right timing, and it wasn't the right thing. It was in poor taste. All pure intentions, but sometimes you don't hit the bull's-eye, right?

In truth, looking back since Gal posted it on Instagram in March 2020, the cursed video has only aged worse to the extent that, in a way, its almost swung back round to camp. In a little intro Gal sighs as if she hasnt seen another human soul in months, when in fact shes in day six of quarantine. She then says the past less-than-a-week-of-isolation has got her feeling philosophical. The deep mind-blowing philosophical realisation? The virus affects everyone. Between Sia over-singing the hell out of her two lines to Mark Ruffalos struggle to figure out his selfie camera angles, the video is essentially the equivalent of those 1 like = 1 prayer posts your aunt still shares on Facebook.

Though the intention behind the video may have been sincere, watching the ridiculously rich act like the pandemic had put us all in the exact same situation and that the only things they had to contribute were vibes and positive energy felt in pretty poor taste. Especially when other celebs, like our queen Britney, were offering struggling fans money. As i-D editor Risn Lanigan wrote at the time: Rather than rushing to push content into the world which doesnt actually help anyone, it might first be best to take some time and consider how your platform, and your millions of dollars of income, could be put to better use.

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Gal Gadot officially regrets the cursed Imagine video - i-D

Did you know that we take 12-20 breaths per minute on average? Its amazing to think that we have the natural powers to thrive simply by taking deep full breaths throughout our day. This is called paced breathing, which is slowing your breath down mindfully to focus on the length of the breath.

The purpose of our breath is to transport oxygen to our cells and to get rid of waste, such as carbon dioxide. Science reveals that your breath is an access point to regulating your nervous system. For instance, when we breathe steadily we can calm our nervous system. When we hold our breath, we build up carbon dioxide in our body, which causes cells and the respiratory center of our brain to become distressed.

Paced breath has the potential to calm your mind and body. This type of breathing exercise can be used in a pinch when youre feeling overly exerted, anxious or distressed. Paced or slower breathing practices support greater brain function, an improved mood, hormone balance and the overall feeling of wellbeing.

Take a moment to listen to Dr. Tracy Gaudets 8-minute video, where she shares more about how breathing helps with healing and stress reduction. Dr. Gaudet introduces the 4-7-8 breathing technique to bring the body, mind and spirit back to a more balanced state. This technique focuses on paced breathing, allowing your exhale to be longer than your inhale. It can create a sense of relaxation in the mind and ease distress.

Find a quiet place to practice, make sure youre seated comfortably with good posture, and try to keep your focus on your breath. If you do lose your focus during the practice, just simply return to your breath.

For more information on self-care through the Whole Health Components of Health and Well-Being, check out our videos here: Whole Health Videos Whole Health (va.gov).

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Live Whole Health #105: Paced breathing - VAntage Point - VAntage Point Blog

The Palo Alto Baylands are roughly three square miles in area, a little corner of relative wildness carved into the deep south end of San Francisco Bay where 15,000 years ago Columbian mammoths and dire wolves roamed a grassy river valley. Within the wetlands, a cement overflow channel fills with floodwater during heavy rains. A water treatment plant hums steadily and a drainage pipe, still wet with raccoon tracks from last night, sieves salt water into the wetlands. But between the channels and pipes, the Baylands are snarled with small trees and tall grasses gone blond with summer heat: perfect habitat for Urocyon cinereoargenteus townsendi, the Townsends gray fox.

Gray foxes are elusive but not rarein the last year alone, citizen scientists logged nearly 350 sightings of foxes on the iNaturalist biodiversity map of the greater Bay Area. Families of foxes have resided on the Facebook headquarters campus since it opened in 2011, gaining a broad online following of enthusiasts. In 2015, a solitary gray fox became a local news celebrity at San Franciscos Presidiothe first sighting within the park in over a decade. (Around the early 2000s coyotes, which are not above making a snack out of a fox, began making a comeback in the city.) But the Palo Alto Baylands, one of the largest fragments of intact marshland remaining in San Francisco Bay, are the nucleus for what we know about the local lives of these shy animalsin the same way that Tanzanias Gombe Stream National Park became the geographic heart for the worlds understanding of wild chimpanzees. And just as Gombe had Jane Goodalls sharp-eyed attention, the Baylands have their own documentarian, too.

Bill Leikam, the fox guy, unlatches the casing for one of his wildlife cameras in the predawn gloom just past the end of Palo Altos Embarcadero Road. The smell of the marsh settles around us: bitter willow, pungent eucalyptus. The coffee hasnt yet hit my bloodstream, but Leikam deftly slides out the memory card and inserts a new one with the spry fingers of someone accustomed to rising early. For 12 years, Leikama high school English teacher turned trailblazing citizen scientisthas watched the Baylands gray foxes. The foxes, indisputably, have watched him back.

Leikams pointing finger throws a heavy shadow across his headlamp beam as he gestures toward the brush at the edge of the path, showing me where, generations ago, he first met Squat, an inquisitive fox that allowed Leikam to linger and watch him go about his daily deeds. Leikam assigns names to the animals he watches: a warmer kind of science than numbers. Squat, Leikam tells me, taught me the basics of being a fox.

The observations that Leikam makesdutifully, every day at dawn and duskare examples of ethology, the study of animal character. The earliest ethologistsNikolaas Tinbergen, Konrad Lorenz, Karl von Frischwere interested in individual variance. Like butterfly collectors, they wanted to catalog the dazzling diversity of animal behavior not as measured in a lab, but as witnessed in the full and complex context of the natural world. When they were jointly awarded the 1973 Nobel Prize in Physiology or Medicine, it was for their work in decoding the information that animals pass to each other. Ethology, even now, says Robert Sapolsky, neurobiologist at Stanford University, is the process of interviewing an animal in its own language.

Every month, Leikam types up his field notes, and they have become a chronicle of family dramas and tender gestures and nightly hunts. Leikam knows where the foxes nap in the crooks of trees, anticipates their shift from syrupy summer fruits to the rich meat of their winter diet, watches their tails sweep from side to side when they are happy, sees where they bury their food and cleanly mark the edges of their territory, listens to them call out to one another in hoarse and raspy voices. The Baylands landscape is pressed deeply with the prints of generations, and Leikams reports are enough to fill a textbook. But, much as naming the animals shifts the relationship between scientist and subject, Leikams intimate and long-spanning observations shift the focus of natural history from that of understanding species to that of understanding individuals, with interwoven communities and kaleidoscopic nuance. When specific populations are watched with a patient gaze, generalities come apart, Leikam says.

It was in 2014, when December was drawing new grass up through the Baylands mud, that Leikam first came to understand how different foxes are from one another. Rain had flooded a low-lying area beneath a tangle of willow branches, and Leikam had sloshed through it on his way to his next field camera. But three foxesall following him, as the foxes in the Baylands often did for Leikams daily roundshesitated. Gray foxes do not like water. Leikam watched each fox approach the dilemma independently. A teenage pup splashed through water to catch up with Leikam, but Dark Eyesthe alpha female of the whole regionstuck to the edge of the puddle, avoiding the wettest places. Meanwhile, Cute leaped sideways to a low bough and threaded her way across the flooded area along tree branches, keeping her paws dry. Leikam used to think that foxes were running on instinct, he confides as we scuff across the now-dry puddle, but theyre as individual as you or me. They can make choices about how they want to behave, and they can also make choices about the futureLeikam has watched the foxes that often accompany him at a curious distance on his morning rounds take shortcuts in order to meet him at his next wildlife camera site: evidence that they can remember, foresee, strategize, and plan.

The gray foxes of the Baylands, with their bright minds and curious behavior, have shown Leikam how to be a fox, but the rulebook is full of exceptions. Out in the marsh, near the tall eucalyptus west of Charleston Slough, Little One and Brownie raised two litters together. Their family was the first documented fox family in the area with a helpera lone female, often a grown pup without her own territory, who sticks around to assist in raising another pairs pups. Since that time, other helpers have been observed, and successful litters have been raised with their assistance. Little One couldnt have anticipated that Brownie would disappear one day with Helper and never return. He set up a den with his new mate out among the sweet fennel and wild oats in the Emily Renzel Wetlands. For a long time afterward, Little One would go wandering in that direction, maybe looking for her lost mate, until eventuallyperhaps understanding what had come to passshe crept away. Gray foxes are socially monogamous for life, meaning they stick with their partners and work together until death parts them. Studies have shown that occasionally gray foxesmale and female bothwill stray from their territory to mate with other foxes during the breeding season, but they return and care for their young together, often exhibiting extraordinary tenderness. Brownies divorce from Little One was something different, and in Leikams experience, unprecedented.

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The spectrum of fox behavior is not unlike the landscape these animals inhabit in the Baylandswell-traveled trails, with a tangly wilderness of possibilities on either side. Alongside the occasional infidelity, theres a capacity for deep family bonds. In 2013, among the dry willows on the Matadero Creek floodplain, two siblings learned together how to be foxes, strong and limber. Bright Eyes would leap at her brother Dark Face, who would spin and run toward her. They would skate to a halt, facing each other with bobbing heads, then leap again into the chase. Together, they wrestled beneath the trees and wove through the dead branches like dancers.

When Leikam found a bundle of fur by the side of the road in the early hours of September 1, 2013a female gray fox knocked lifeless by a car in the nightit took him three days to acknowledge that it was the body of Bright Eyes. During that time, neither of Bright Eyes parents emerged from the bushes as usual to greet Leikam on his morning rounds. Her brother would return often to the floodplain near the trees where he and Bright Eyes used to play, looking out across the wide marsh. He limped on his left leg, perhaps clipped by the same deadly car as the siblings bounded together too close to moving traffic. Dark Face moved slowly, heavily, as if weighed down. They were family, Leikam wrote of the separated siblings, in the deep meaning of that word.

Both gentleness and violence punctuate the lives of gray foxes. A fox kiss is a universal gesture: a damp and delicate touch, nose tip to nose tip. Conversely, combat between foxes is ferocious. A fox fight is swiftin the time it takes to draw a deep breath, whole wars are begun and finished. Squat, the presiding Baylands alpha male, first presented his daughter to Leikam when she was still a pup. Squat emerged from the bushes and sat at the edge of the path, glancing behind himself until, a few minutes later, a pudgy little fox materialized. She touched snouts with her father and looked across the path at Leikaman introduction, of sorts. Bold soon earned her name, appearing alone to daringly watch Leikam while her siblings stayed hidden in the brush.

But when the time came in 2011for Bold to claim land for a den of her own, rather than dispersing, as is typical, she approached Squat and challenged him for his territory. All teeth and claws, Bold fought and defeated her father in mere seconds, taking possession of the same land where Squat had raised her. In the unruly moment that the fight lasted, Leikam captured a photograph of the violence: Bold airborne, mouth open, her teeth as luminous as a new set of knives. It was the stuff of Greek theaterthe ticking of the generational clock, a fathers conquest, the rise of a new empire. It is also the stuff of ethological breakthroughsbehavior like Bolds is phenomenally important in understanding social dynamics, says behavioral ecologist Marc Bekoff, professor emeritus at CU Boulder, who leans forward excitedly as he listens to me relay the story after I return from my adventure with Leikam. An observation like that could generate 20 theses in a heartbeat.

After overthrowing her father and claiming her natal territory, Bold became Mama Bold, and together she and her mate Gray reared families of their ownfive pups nearly every year, raised on warm milk and the dark meat of woodrats in the brushy neighborhood of Fox Hollow. The pups sharp teeth drew blood, so Mama Bold would often lie a few yards from the den. Gray would wander the marsh, returning with food, and he tended to parenting tasks in the den. When the pups were hungry, Gray would approach Mama Bold with a soft nudge, and she would return to feed them. Together, they taught their young how to climb trees, how to hunt. In quiet moments between duties, when Gray lounged in the clearing, Mama Bold would snuggle against him and lay her chin across his warm belly. Curled against each other like this, they would nap.

Betrayal, altruism, loyalty, grief. These are recognizable behaviors that reveal not only sharp intelligence, but a nuanced capacity for emotion that eclipses raw instinct. If gray foxes can abandon mates, mourn lost companions, care for young that are not their own, and live long lives in unbroken devotion to one another, perhaps the rulebook needs to be rewritten with attention paid not just to natural historyhierarchies, life spans, dietsbut with a deeper consideration for the life of the mind. Leikam has come to understand that these animals lead complex emotional and intellectual lives. He once watched a fox pup as it slept. All of a sudden, his hind leg went pop, and it was moving, and thats a signal that theyre dreaming I said, Whats going on in that little foxs mind?

Its a mystery Leikam is still working to unravel. He suspects that foxes might experience their world synesthetically: that is, that they blend their senses and might be able to smell sound or hear odor. With such keen tools of perception, a foxs mind might work in ways that science has yet to measure. Leikam has watched, for example, solitary foxes facing a frightening or challenging experience. Other foxes seem to know whats happening, and will arrive in times of need from long distances. What does a fox dream of? What can these animals hear or feel that we cannot?

These questions get at the heart of ethology, a field that has roots not just in muddy-booted natural history but in the study of the mind. Mid-century scientists called behaviorists were frustrated by the soft science of psychology, which at the time was a much more introspective, philosophical field than it is today. The behaviorists were keen to make psychology quantitative, to slim behaviors down into universal rules that could be applied across all species. Ethology arose in resistance to this. Where behaviorists sought clean uniformity, ethologists paid attention to variation. Where behaviorists tried to pinpoint rules, ethologists made theirs the study of exceptions. Their questionsthen and nowconsider individual motivations and individual minds. What its all about, says Stanfords Sapolsky, is recognizing that other species out there are functioning in sensory modalities we cant even guess at.

Leikam didnt think much of it when, in 2016, he started noticing goopy discharge in several foxes eyes. He made note of it, but he had witnessed the staggering strength of foxes immune systemstheir ability to heal swiftly from injured paws and the raw wounds from fights. Yet by the end of the year, 25 Baylands foxes turned up deadwiped out by a highly contagious viral infection called canine distemper.

Gray. Brownie. Little One. Dark Eyes. Mama Bold. Foxes disappeared entirely from the areawhole families, lost lineages. In their absence, Leikam watched the marsh change. Woodrats, jackrabbits, and field mice exploded in number. The meadows and trails busied with lizards, gopher snakes, gophers, voles, and squirrelsall of which Leikam watched transform the vegetation of the Baylands. He describes gray foxes as keystone predators: animals that, by virtue of their diet, keep whole ecosystems in check. Observations like Leikams lay the groundwork for understanding those systemic balances. You need these data in order to do behavioral ecology, Bekoff says. The fieldwork, he says, is foundational.

For two years and one month, Leikam kept up his daily walks, hoping for a reappearance. Occasionally, video would show up on one of the feeds: a vagabond fox moving through in the night, dark and smooth. But it wasnt until February of 2019 that foxes finally returned to stay. Now LaimosGreek for long neckand his mate Big Eyes have taken up residence at Matadero Creek. They have yet to have any pups.

This morning, Laimos approaches us in the dry overflow canal and sits nearby, watching us with glittering eyes. He yawns. Does the future of fox-kind in the Baylands weigh on his gray shoulders? Leikam would argue that more foxes will come, but only if corridors between fragmented marshy refugia can be planted with fox-friendly brush, and only if tracking collars can be used to help us better understand fox dispersal in the few remaining wildlands of the South Bay, both the work of Leikams nonprofit Urban Wildlife Research Project.

Gray foxes evolved between 8 and 12 million years ago, when the Grand Tetons first began forming and when disorderly Sierra Nevada canyons still filled with down-rushing volcanic lava flows. Gray foxes have been on this planet longer than all other canids; in evolutionary circles, they are called the basal canidthe original dog. Since their ancestry is rooted in a time before other canines, they cannot interbreed with other species in the manner of coyotes and wolves or wolves and domesticated dogs. To look at a gray fox is to look at an unbroken genetic lineage that goes back perhaps as far as 12 million years. A gray fox is an ancient thing.

During the last great ice age, the climate swings of the Pleistocene divided eastern and western gray fox populations. California became a refugium where species took shelter from an increasingly arid continent and from an ice sheet that pressed across middle America like a two-mile-high earthmover.

Considering the landscape of the Bay Area todaypartitioned by highways, stitched together by bridges, patchworked with neighborhoods and tech empiresperhaps green spaces like the Palo Alto Baylands serve as another sort of refugia. Hemmed in on all sides by a landscape that looks very different than it did at the end of the Pleistocene, do gray foxes here continue to adapt to their environment? Occasionally, Leikam receives notes from biologists elsewhere, suggesting that seasonal diets or behaviors of the foxes they study are different from the findings in Leikams reports. The lives of Bay Area gray foxes, it would seem, are unique to Bay Area gray foxes.

Slow, observant science like Leikams is rare and important. Where other disciplines might seek averages, ethology recognizes specific stories. It is a tool for understanding localized natural history, intimately. Linger long enough, and the shy gray fox might reveal something to the patient observer that it has never shared before. Interview them in their own language, and these primeval first dogs might still have lessons for us: how to be a fox; perhaps how to better be human.

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How to Be a Fox: Secrets from the Baylands - Bay Nature