Monthly Archives: February 2021

From the start of the coronavirus outbreak, technology from Illumina has been at work helping defeat the pandemic. As a result of two Chinese university teams using the US biotechs sequencing equipment, the genome (or genetical material) of the coronavirus was published on January 10, 2020 and vaccines from Oxford University/AstraZeneca, Moderna and Pfizer-BioNtech vaccines were designed within days of this blueprint being revealed.

The latter two are the worlds first genome-based vaccines and have been developed without the companies ever needing to have the virus on site. Sequencing is instrumental to understanding not only the make-up of the virus, but its epidemiology, how it mutates, how it evolves, and also to develop a vaccine for it, says Illumina CFO Sam Samad.

One year on and sequencing the virus is as important as ever in the pandemic fight. Illuminas technology is powering genomic surveillance in countries around world, such as at the Sanger Centre in Cambridge where the COG-UK team identified the new B1.1.7 variant; and in the US where Illumina is working with the US CDC and the company, Helix, to plot the path of new variants across US States.

Our ability to use sequencing to do surveillance, is critical. We need to understand how the virus is mutating and how its also transmitting across communities. Surveillance will also tell us whether the virus is evolving to escape the vaccines that are now being delivered in most countries.

That really underscores the importance of our technology in this fight, says Samad, who joined the San Diego, California-based firm at the start of 2017. Other pandemics will happen in the future, so the question also becomes how do we prevent them? How do we, catch them before what happened with Covid repeats? asks the Canadian.

Illumina was founded in 1998 based on BeadArray technology discovered at Tufts University. Arrays require a prior knowledge of the genome of the sample being investigated. In 2007, Illumina acquired the UK-based company, Solexa, for its next generation sequencing (NGS) technology which Illumina has gone on to develop. NGS doesnt require any understanding of the sample to be analysed and can work out the full genome of any organism.

Illumina has gone on to develop a range of products servicing the sequencing, genotyping, gene expression and proteomics markets has resulted in the rapid growth of its share price- resulting in the firm having a market value of $54bn by the start of the year.

Major sites have been developed in Foster City, near San Francisco, Cambridge in the UK focusing on R&D, and an Asian hub in Singapore combining shared services and manufacturing functions, as well as a major plant in China.

Infectious diseases is just one area of focus for Illumina. Another is oncology, where the company is working with a number of pharma and biotech companies to develop cancer testing to determine which medicines are best for which cancer patients. NGS is also fundamental to identifying the cause of rare genetic diseases in families; and to understanding the chromosomal health of an unborn baby through non-invasive prenatal testing (NIPT).

Oncology is now our biggest area, but we also work in genetic diseases, and reproductive health and non-invasive prenatal testing, taking sequencing and evolving it into a standard of care in health systems around the globe. Just shy of 50 percent of our revenues are in the clinical setting, says Samad.

A big change in Illuminas offering came five years ago when it pivoted from a mainly research approach, supplying instruments, reagents and consumables to academic labs and large genome centres, to focusing on clinical applications of genomics. It acquired Verinata Health, a leading provider of NIPT, and with it, NGS and Illumina started to become as familiar to clinicians as they had been to scientists.

The speed of development reflects the need to innovate in a fast-changing area of science. I think we have an obligation through our technology to move fast.

What you thought was possible 10 years ago, is completely different than what we think is possible today. Who would have thought that through sequencing, we could offer early screening to potentially predict, find it and cure cancer before it becomes deadly, he says.

The pace of development was challenged by the coronavirus pandemic where the majority of staff had to move to remote working but having lab staff designated essential workers meant operations could continue unabated. It meant R&D and manufacturing staff could come to the labs to continue work, says Samad.

A colour coding of sites, from green meaning nothings wrong to red, requiring all staff working remotely, except for essential functions was devised. At some point, most of our sites became really red and orange, resulting in 7,500 out of 8,000 staff working from home, but everybody handled it really well, he says.

Samad came into Illumina with a skill set in finance developed across the healthcare sector. After completing a finance degree and MBA at McMaster University in Ontario, he joined US pharma giant Eli Lilly where over the course of 12 years he rose from being a financial analyst to finance director of the groups Swiss operation before finishing as CFO of Eli Lilly Canada.

It was an opportunity to develop the rigour and discipline demanded by working in finance in a global player. I cant emphasise enough how important it is to get some experience in a large, well-run disciplined institution like Eli Lilly. It was really, really important for me just to get those building blocks and foundations in my career, he says.

But it was at Cardinal Healthcare, another major US player, that he went on to group leadership roles, as CFO of its pharma segment and then treasurer of the whole firm, positions demanding strong decision-making. If you get it wrong, you can send the company into a tailspin that might mean it goes bankrupt, because youre talking about debt issuances and capital availability, he says.

There was also the challenge of addressing the expectations of debt investors, where conservatism pays off in terms of how you manage your cash position, adds Samad.

The opportunity to become group CFO at Illumina offered the chance to join a fast growth company with an offer based on cutting edge science. I felt there was so much runway ahead as the space was so under-penetrated, he says.

What he could bring was the discipline needed for a business that had listed 20 years ago but he says was still operating in an accelerated growth, start-up mode, with some processes not having been fully built out.

What Samad sought to develop was a stronger engagement between the finance team and the rest of the business in an organisational structure for optimally supporting the business through single point accountability.

We needed, for example, a research and development (R&D) person in finance that supports the R&D organisation and another in finance supporting the commercial organisation, and another specifically supporting the product side of the business.

The first six months of Samads time finessing the finance function was a process of evolution. You dont get a structure right the first time, you do it incrementally, and you do it over time, he says.

A major innovation was devising exhaustive and comprehensive dashboards on data visualisation software Tableau covering everything from revenues to balance sheets and R&D. Its reviewed by the executive team twice a month, but I want people to have access 24/7.

That helps with speed of decision making, but it also helps in terms of managing bandwidth and understanding resource constraints on the organisation. because youre not having to ask people all the time to run reports for you, adds Samad.

Despite the challenges presented by the coronavirus pandemic, in September 2020, Illumina announced the proposed $8bn acquisition of cancer screening specialist Grail. The deal raised some eyebrows in the market given that Illumina had created and spun out Grail just four years previously, but the move reflects the willingness to consider any action that can bring together the right ingredients for value creation, even if it appears unwieldy.

Samad says the decision reflects a strategic assessment that Grails proposition today: using blood-based tests known as liquid biopsies to catch cancer early, would fit well in the group, after we had stepped out of the space, to allow it to thrive and evolve through $2bn of R&D funding.

Following fantastic, really promising results for the Grailtests, the decision was taken in late 2019 to acquire the business to grow Illuminas footprint in cancer. But what was crucial to explain to the market was that its a $60bn target market thats totally incremental to us, says Samad.

You need to set the stage in terms of how you explain it to your shareholders, to make sure they get why we can accelerate this market with our commercial capability, with global our operations, he adds.

Samad says he balances him time between priorities such as explaining Grail the story to investors, to focusing on areas for funding over the next five-year cycle.

These are often very difficult conversations, that are always emotional. So you need your people to help and you need to have a good rapport with your executive team, your peers and partners to do that as well, he says.

He says that without his key staff in accounting, treasury, FP&A, and leaders across global regions, I wouldnt be able to have the capacity and bandwidth that would allow me to focus on the key things, he explains.

Samad says closing the Grail deal created a unique set of challenges with the restrictions that we have in terms of travel. But a big focus of ours is that even in times of global crisis, we are really focused on making sure that we continue to find opportunities to move our strategy forward.

We believe these times present a unique opportunity for companies that really focus on executing on their strategy. If they are bold and make big steps, they will come out on the other side of this ahead, he adds.

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Illumina CFO on using genome tech to beat pandemic - Financial Director

ILLUSTRATION: MICHELLE KONDRICH

The availability of a fully sequenced human genome and genome-wide analyses of genetic variation have made DNA-based ancestry tests possible. These consumer DNA tests are now widely marketed as a way to discover or confirm family history. But what do they really tell us about our past, and what do they leave out? We asked young scientists to tell us about their family traditions, stories, and culture, and how they understood their DNA test results in the context of their lived experiences. Their stories are below. To read more reflections by young scientists, find past NextGen Voices pieces at https://science.sciencemag.org/collection/nextgen-voices. Follow NextGen Voices on Twitter with hashtag #NextGenSci. Jennifer Sills

My family comes from Jamaica and the Virgin Islands. There is no meal I would rather have than my mom's home-cooked traditional Jamaican food. Now living in Florida, my mom grows many fruits and vegetables native to Jamaica in a garden that occupies her entire yard. When I visit, we spend most of our time together outside picking fresh mangoes, ackee (a tropical fruit grown in Jamaica), or whatever else happens to be in season. On Christmas, she makes oxtail (a kind of beef stew, my personal favorite), fried dumplings, and ackee with saltfish (its traditional complement of salted cod). These foods are well-spicedalthough not always spicyand flavorful.

Where my family originated is mostly hearsay, and the full history beyond a few generations is hard to trace. My DNA test results confirmed that we have some background in Europe and likely moved to the Caribbean through the slave trade. The details echoed a story on my mom's side of the family that one of our ancestors was the child of an Irish slave master and a woman he enslaved.

I have mixed feelings about the business model of consumer DNA test companies, which make their profit based on the use of others' genetic informationin my mind, the most personal information one can share. However, my mom really wanted me or my dad to do the test to see how that side of our ancestry looked. I chose a company that gives users more control over who can access the results. Of course, these tests are not as accurate for those of us from non-European backgrounds, but the results were roughly what I expected, and it is humbling to think about where our family began compared with where it is now.

Gregg Duncan Fischell Department of Bioengineering, University of Maryland, College Park, MD 20742, USA. E-mail: gaduncan{at}umd.edu

My family is Han, the largest nationality of China. Like most families in China, we celebrate the Spring Festival (Chinese New Year) by gathering together to make and eat jiaozi (dumplings filled with vegetables and meat), which are shaped like ancient Chinese gold ingots to symbolize wealth. We hang festival couplets (two lines of poetry with the same number of words) that are painted along with intricate designs on red paper, and we put red lanterns and red candles on display throughout the house; the decorations symbolize happiness and protect us from the mythical monster named Nian, who is said to be afraid of the color red. While we wait for the New Year to arrive, we listen to Hebei Bangzi, the local opera, which sounds similar to the Beijing opera but is more difficult for people outside Hebei province to understand because the singers use pronunciations unique to the region. In my hometown (Shijiazhuang, Hebei), people of the same surname gather together to extend best wishes to their elders before the first sunrise of the new year.

Such traditions are a reminder that my surname (Ji) is not common in China. I hoped that finding out more about my family's origins would help to explain my unusual name. My DNA test results told me that 46.34% of my genome came from North China (Han), 20.13% from South China (Han), and 12.21% from Northeast Asia (Japan). I was disappointed that the results contained no detailed information that I found useful. I do not know how many Chinese people have a genetic pattern similar to mine, andunlike scientific researchthe company did not give me the raw data of my genome. Without more information about how the company analyzed my genomic data, I don't know what conclusions I can draw or even whether I should believe the test results.

Yongsheng Ji Division of Life Science and Medicine, University of Science and Technology of China, Hefei, Anhui, 230026, China. Email: jiys2020{at}ustc.edu.cn

Fifteen years ago, I probably would have said that my family didn't have a French cultural identity, despite being raised in France. Today, after having been expatriated 10 years in New Zealand, I can confirm that we have a strong French cultural identity, especially when it comes to food. Yet, after we returned to France 3 years ago, our attachment to our home country and its culture and traditions did not feel quite the same. I believe that we unintentionally took bits of New Zealand back to France with us.

Our ever-evolving celebration of Mardi Gras encapsulates our cultural journey. Before our move, we had always celebrated the French holiday in its traditional (if less religious) form. Around the end of February, we would make and eat loads of French crpes, and kids would dress up in festive costumes and attend the carnival. After our move, we discovered that New Zealanders do not observe Mardi Gras, so we adopted a different yet similar tradition, which was brought to the country from overseas and stuck: Halloween. Every year on the 31st of October, my eldest boy dressed up in a scary costume. But because good food is so deeply rooted in our culture, Halloween candy didn't feel sufficient. To supplement the prepackaged treats, we created our own tradition of the Halloween scary lunch. Each year, I would prepare a lunch box filled with funny and scary little monsters, skeletons, and ghosts made of pancakes, carved fruits, and (for the mummies) baked sausages in pastry strings.

Now back in France, we have resumed our celebration of Mardi Gras in February. The kids dress up for school and for carnivals, just like Halloween, but with an emphasis on festive instead of scary, and we make crpes, as we've done in the past. We've also kept our own multicultural family traditions. To adapt our New Zealand Halloween lunches, we now have a Halloween-themed French dinner in October. We've also updated the tradition of hiding a fve (trinket) in our galette des rois (king cake) by using a koru necklace (a traditional kiwi artifact) instead.

Our unique and changing traditions showed me that we could be open to incorporating new values and ideas when we learned the results of our DNA tests. My husband and I are both researchers in ecology and environmental genetics, manipulating DNA data daily and studying insect population genetics. It seemed only natural that we would want to see our own DNA test results. We originally thought that the genetic admixture might be quite high within our family home given that we were born 12,000 km apartI grew up in northern France, and he was raised on the French island of La Runion in the Indian Ocean. We were quite surprised by the results. For instance, I learned that I had ancestors from Italy and Scandinavia but very little French or Western European lineage, whereas my husband, despite being born in the Southern Hemisphere, has more Western European lineage than I do. (His results could perhaps be explained by the fact that half of the first settlers in La Runion were from Brittany.) Although my husband has ancestors in many parts of the world where I do not (such as India, Africa, and Indonesia), we share an unexpectedly high rate of ancestry from the Iberian Peninsula (Spain and Portugal). The results have not changed our lives, but it is interesting to know that, genetically, we are more an Iberian family than a French one! We now want to travel to and discover more about the culture of these southwestern parts of Europe and pass on this heritage to our children. As ecologists, we are curious about the natural and geological histories of the Iberian region, but we would make food an important part of the trip as well. They may not have French crpes in Portugal, but I have heard that the delicious bolo lvedo (Portuguese muffins) are not to be missed.

Marie-Caroline Lefort Cellule de Valorisation Pdagogique, Universit de Tours, Tours, France. Email: marie-caroline.lefort{at}univ-tours.fr

As a Jewish woman born in Iran and living in Israel, I feel connected to the ancient history of my people. Because it is rare to find an Iranian woman in science who keeps Jewish traditions, I feel a responsibility to manifest all the good that is in each part of my background.

My family celebrates the traditional holiday of Rosh Hashanah (the Jewish New Year). Wearing white clothing to symbolize purity, we light candles and look into the flames as we give thanks and ask for blessings in the coming year. We celebrate this contemplative holiday with a festive meal steeped in symbolism and tradition. We eat apples dipped in honey and pomegranates to symbolize our hopes for a sweet, peaceful, happy new year that is full of good deeds. The honey represents sweetness, and the apple tree is the only tree that has more fruit than leaves, reminding us that we should maximize our purpose in this world. The numerous seeds in pomegranates, a native fruit of ancient Persia, symbolize the many good deeds we should carry out during the coming year. We also make a traditional Iranian-Jewish stew out of quince, a native fruit of west Asia (including Iran and Israel) that looks like an apple. The sweet smell fills the entire house with a magical floral and fresh perfume. During Rosh Hashanah, the shofar (an ancient musical instrument typically made of a ram's horn) is blown 100 times. The sound marks the time to make our wishes for the new year, which we read in Hebrew.

My DNA test results show that I am mostly Persian, with a very small percentage (0.8%) of Egyptian in my ancestry. The data echo the Biblical and rabbinical stories that I consider my roots. Our cultural history tells us that our ancestors were in ancient Egypt for hundreds of years before moving to Israel with Moses. In 722 BCE, the Jews were exiled from Israel to other regions, including Iran. My father was born in a city that was first settled by the exiled Jewish people from Israel, and my mom is from a city that is well known in Iran as the site of the story of Esther and Mordechai, traditionally told during the holiday of Purim. My family moved to Israel after the revolution in Iran in 1979. My DNA results mirror both these ancient tales and my own family's story.

Ruty Mehrian-Shai Pediatric Hemato-Oncology, Brain Cancer Molecular Medicine, Sheba Medical Center, Ramat Gan, 52621, Israel. Email: ruty.shai{at}sheba.health.gov.il

I've always struggled with being identified as simply Indian. My name reflects my Indian heritage better than I do, as a Montreal-born, New York City native living in Louisiana. No DNA test could reflect the mix of American and Indian cultural practices that my family has created. Take, for example, American Thanksgiving, which my family co-opted when I was young and combined with a traditional West Bengali feast. At our table, we served the turkey alongside traditional Indian luchi (oil-fried puffed dough) and fusion dishes such as vegetarian shepherd's pie with Indian spices. Because my birthday falls near Thanksgiving, the meal was often followed by a turkey-shaped ice cream cake, Indian sweets like jalebi (a bright orange pretzel of fried sweet dough), gulab jamun (fried syrupy-sweet milk balls), and a spiced tea. We did adhere to the American tradition of overstuffing ourselves with food.

During the holiday, we listened to Bollywood pop, with high-pitched Indian women singing in Hindi or Bengali. Later in the season, my father would mix in some Nat King Cole or Frank Sinatra, or we would play an album from jazz pianist Vince Guaraldi. Being in Queens, I would always play Christmas in Hollis by the Queens-native hip-hop group Run DMC. My parents enjoyed it about as much as I did their Bollywood music, which is to say, not much.

In December, the large extended family of cousins, uncles, and aunts (all with a different honorific based on their birth position relative to my parents) would come over, each removing their shoes at the door out of respect. The men, in sweaters and ties, played bridge cross-legged in a corner on the floor. The women, in saris and their finest gold necklaces and earrings (gaudier than any of the jewelry worn by the hip-hip artists I worshiped), congregated in the dining area, where they teased each other, told stories in Bengali, and prepared meals. Food was served constantly from the moment the first guests arrived until they left. The smell of food cooking, mostly oil and spices, radiated and permeated through every fabric of the house. Chatter, the sounds of food frying, and playful arguing filled every room with noise. Our home was festively decorated; Santa Claus had equal billing with Durga, Kali, and Ganesh.

The kids watched American football or challenged each other to an Indian game called carrom, which is similar to billiards but played on a flat smooth table on the floor. Players use their fingers to flick flat wooden discs into different corner pockets. We would play different tournament styles and use a mix of Bengali and English to taunt and tease each other over missed shots or lucky wins.

Before our current chapter as Americans, my family's Indian past stretches back to time immemorial, but India has a complicated history of invasions and rule. I hoped a DNA test would help clarify some ancestry questions. I wanted the results to say 25% Genghis Khan, 25% Gandhi, 25% Alexander the Great, and 25% unknown. What I got was 64% Central Asian, 30% South Asian, 3% Eastern European, 2% Southeast Asian, and 1% Siberian. So, I could claim Genghis, Gandhi, and Alexander! But of course, not really. I wondered when and where the mingling of my different geographic ancestors took place and if the results were more a reflection of the current genetic reference populations in those areas. The DNA results didn't make me feel differently about my identity, and they were not as interesting as the results I received from a genetic profile that revealed an inversion in one of my chromosomes. That genetic result made me realize how hardy our genomes are and how similar we are as humans; even the 1% or so that makes each of us unique is almost meaningless when considering the bigger picture.

Prosanta Chakrabarty Louisiana State University Museum of Natural Science, Baton Rouge, LA 708033216, USA. Email: prosanta{at}lsu.edu

ILLUSTRATION: MICHELLE KONDRICH

Born in South America, I identify as Latina and have always been aware of my mixed ethnicity. My family's celebration of Christmas and Novena (the previous 9 days, an important observance in Colombia) exemplifies our love of food, music, and dance. During the first 8 days, family and friends meet at different houses to share deep-fried cheesy dough and sweets. On Christmas day and the morning after, we eat homemade Colombian tamales wrapped in plantain leaves and boiled for hours, and we drink hot chocolatefirst adding salty cheese to the mugs and eating it with a spoon once it has melted (a delicacy unique to Bogot, Colombia's capital). Sometimes we also eat cheese arepas (flat corn bread) and almojabnas (cheese bread of Spanish-Arab origin). Meanwhile, my mum prepares about 20 liters of her famous ajiaco, a traditional soup from the Bogota plateau. She uses three kinds of potatoes (one of them endemic to the Northern Andes), guascas (Galinsoga parviflora), corn, chicken, capers, and cream. Toward the end of the day, the whole family gathers for a bowl of ajiaco. We admire our araucaria tree, decorated with lights and ornaments, and the creatively assembled nativity scene (often including llamas, lions, jaguars, and the occasional dinosaur) while waiting for midnight to come.

My family seems to carry music in our blood. There is always a moment when my uncle plays the guitar and everyone else joins in with percussion and voices, singing the melodies of cumbia, vallenato, and bambucomusical styles incorporating strings and accordions from Europe, wind instruments from Indigenous communities, and African drums. The upbeat tunes belie the bittersweet themes in the Spanish lyrics. Soon, everyone is dancing to the energetic, fast-moving rhythms of cumbia, salsa, and merengue. Salsa originated with the Latin and Afro-Latin son cubano and jazz musicians from the Bronx in the United States. The music later made its way to Colombia, where it developed into something new, incorporating cumbia and vallenato elements and a faster dancing style.

I took a DNA test because I work in the fields of population genomics and phylogenomics and thought it would be fun to see my own genome sequences. Half of the sites sequenced on my genome were assigned to populations in Spain, Morocco, and West Africa; the other half to Native American populations. The results were not a surprise, but they encouraged me to dig deeper into my family's history. I wish I could learn about and celebrate the Native American traditions of my ancestors, but most were never documented and are now lost. Important traditions are kept in the Amazon regions, such as chontaduro dancing, where communities share the chontaduro fruit (from the Bactris gasipaes palm) and drinks to celebrate abundance and usher in a good fishing season. Traditions around the cassava, plant growing seasons, and hunting also still take place, but because I grew up in the city, I don't feel personally connected to them. I do take pride in using the words from Quechua, Muisca, and even Arabic languages that have been assimilated into Colombian Spanish.

We knew my grandfather was Indigenous from the south (as the government labeled him back in the day), but the DNA test results suggest that our Indigenous ancestry could have been more recent and likely than we thought. I found the test interesting; I received a set of raw data that I can analyze myself, and the results brought my father and me together in a quest for the documents and stories surrounding my family.

Maria Fernanda Torres Jimenez Gothenburg Global Biodiversity Centre, University of Gothenburg, Gothenburg, Sweden. Email: mftorres27{at}gmail.com

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Beyond DNA: The rest of the story - Science Magazine

Our machines could handle thousands or hundreds of thousands, said Dr. Neville Sanjana, a scientist with a lab at the New York Genome Center in Lower Manhattan. So the capacity is just not the issue.

The issue for research laboratories strangely enough, amid a pandemic that has probably infected more than a quarter of New Yorkers is access to samples. In New York, there is no high-volume pipeline of positive virus samples from hospitals or testing sites to research laboratories to conduct genetic surveillance.

Its really just organizing that sample collection that, I think, is whats missing, said Dr. Sanjana, whose research has involved searching for which medicines might block infection by inhibiting the human genes that the coronavirus hijacks.

What is needed, scientists said in interviews, is for the city or another entity to essentially bifurcate the current coronavirus testing process. Each day, tens of thousands of New Yorkers provide swabbed samples, which are generally sent to a few large laboratories for testing. If those labs could set aside a portion of the samples, those portions could later be used for genome sequencing if they turned out to be positive.

Its solvable, but it needs resources and it needs people to coordinate, Professor Heguy said, as she listed the necessary steps: A portion of the original sample would need to be set aside; RNA would need to be isolated from it; and someone would need to transport the RNA samples to a laboratory that does genome sequencing.

The citys goal of expanding sequencing at least tenfold will require enlisting a range of outside laboratories and research projects, big and small. The city anticipates that the largest share of the genomic sequencing will happen at a laboratory in Long Island City, Queens, that is run by a small robotics company.

The company, Opentrons, also runs a facility in Manhattan called the Pandemic Response Laboratory. That laboratory was built last year to help the city solve the testing crisis that emerged during the summer, when big commercial laboratories were struggling to handle the soaring caseload. People were having to wait several days, and sometimes a week or two, for coronavirus test results. The laboratory now tests 20,000 samples a day.

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New York City Barely Tests for Virus Variants. Can That Change? - The New York Times

Twenty years ago this month, the first draft of the human genome was publicly released. One of the major surprises that came from that project was the revelation that only 1.5 percent of the human genome consists of protein-coding genes.

Over the past two decades, it has become apparent that those noncoding stretches of DNA, originally thought to be junk DNA, play critical roles in development and gene regulation. In a new study published today, a team of researchers from MIT has published the most comprehensive map yet of this noncoding DNA.

This map provides in-depth annotation of epigenomic marks modifications indicating which genes are turned on or off in different types of cells across 833 tissues and cell types, a significant increase over what has been covered before. The researchers also identified groups of regulatory elements that control specific biological programs, and they uncovered candidate mechanisms of action for about 30,000 genetic variants linked to 540 specific traits.

What were delivering is really the circuitry of the human genome. Twenty years later, we not only have the genes, we not only have the noncoding annotations, but we have the modules, the upstream regulators, the downstream targets, the disease variants, and the interpretation of these disease variants, says Manolis Kellis, a professor of computer science, a member of MITs Computer Science and Artificial Intelligence Laboratory and of the Broad Institute of MIT and Harvard, and the senior author of the new study.

MIT graduate student Carles Boix is the lead author of the paper, which appears today in Nature. Other authors of the paper are MIT graduate students Benjamin James and former MIT postdocs Yongjin Park and Wouter Meuleman, who are now principal investigators at the University of British Columbia and the Altius Institute for Biomedical Sciences, respectively. The researchers have made all of their data publicly available for the broader scientific community to use.

Epigenomic control

Layered atop the human genome the sequence of nucleotides that makes up the genetic code is the epigenome. The epigenome consists of chemical marks that help determine which genes are expressed at different times, and in different cells. These marks include histone modifications, DNA methylation, and how accessible a given stretch of DNA is.

Epigenomics directly reads the marks used by our cells to remember what to turn on and what to turn off in every cell type, and in every tissue of our body. They act as post-it notes, highlighters, and underlining, Kellis says. Epigenomics allows us to peek at what each cell marked as important in every cell type, and thus understand how the genome actually functions.

Mapping these epigenomic annotations can reveal genetic control elements, and the cell types in which different elements are active. These control elements can be grouped into clusters or modules that function together to control specific biological functions. Some of these elements are enhancers, which are bound by proteins that activate gene expression, while others are repressors that turn genes off.

The new map, EpiMap (Epigenome Integration across Multiple Annotation Projects), builds on and combines data from several large-scale mapping consortia, including ENCODE, Roadmap Epigenomics, and Genomics of Gene Regulation.

The researchers assembled a total of 833 biosamples, representing diverse tissues and cell types, each of which was mapped with a slightly different subset of epigenomic marks, making it difficult to fully integrate data across the multiple consortia. They then filled in the missing datasets, by combining available data for similar marks and biosamples, and used the resulting compendium of 10,000 marks across 833 biosamples to study gene regulation and human disease.

The researchers annotated more than 2 million enhancer sites, covering only 0.8 percent of each biosample, and collectively 13 percent of the genome. They grouped them into 300 modules based on their activity patterns, and linked them to the biological processes they control, the regulators that control them, and the short sequence motifs that mediate this control. The researchers also predicted 3.3 million links between control elements and the genes that they target based on their coordinated activity patterns, representing the most complete circuitry of the human genome to date.

Disease links

Since the final draft of the human genome was completed in 2003, researchers have performed thousands of genome-wide association studies (GWAS), revealing common genetic variants that predispose their carriers to a particular trait or disease.

These studies have yielded about 120,000 variants, but only 7 percent of these are located within protein-coding genes, leaving 93 percent that lie in regions of noncoding DNA.

How noncoding variants act is extremely difficult to resolve, however, for many reasons. First, genetic variants are inherited in blocks, making it difficult to pinpoint causal variants among dozens of variants in each disease-associated region. Moreover, noncoding variants can act at large distances, sometimes millions of nucleotides away, making it difficult to find their target gene of action. They are also extremely dynamic, making it difficult to know which tissue they act in. Lastly, understanding their upstream regulators remains an unsolved problem.

In this study, the researchers were able to address these questions and provide candidate mechanistic insights for more than 30,000 of these noncoding GWAS variants. The researchers found that variants associated with the same trait tended to be enriched in specific tissues that are biologically relevant to the trait. For example, genetic variants linked to intelligence were found to be in noncoding regions active in the brain, while variants associated with cholesterol level are in regions active in the liver.

The researchers also showed that some traits or diseases are affected by enhancers active in many different tissue types. For example, they found that genetic variants associated with coronary heart disease (CAD) were active in adipose tissue, coronary arteries, and the liver, among many other tissues.

Kellis lab is now working with diverse collaborators to pursue their leads in specific diseases, guided by these genome-wide predictions. They are profiling heart tissue from patients with coronary artery disease, microglia from Alzheimers patients, and muscle, adipose, and blood from obesity patients, which are predicted mediators of these disease based on the current paper, and his labs previous work.

Many other labs are already using the EpiMap data to pursue studies of diverse diseases. We hope that our predictions will be used broadly in industry and in academia to help elucidate genetic variants and their mechanisms of action, help target therapies to the most promising targets, and help accelerate drug development for many disorders, Kellis says.

The research was funded by the National Institutes of Health.

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Epigenomic map reveals circuitry of 30000 human disease regions - MIT News

TheWhole Genome Bisulfite Sequencing (WGBS) Marketresearch report thoroughly explains each and every aspect related to the Global Whole Genome Bisulfite Sequencing (WGBS) Market, which facilitates the reports reader to study and evaluate the upcoming market trend and execute the analytical data to promote the business.

Whole Genome Bisulfite Sequencing (WGBS) Market Insight:

Whole genome bisulfite sequencing (WGBS) market is expected to gain market growth in the forecast period of 2020 to 2027. Data Bridge Market Research analyses the market to grow at a CAGR of 12.90% in the above-mentioned forecast period. Increasing awareness among the people regarding the benefits of genome sequencing which will further create lucrative opportunities for the growth of the market.

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The report also inspects the financial standing of the leading companies, which includes gross profit, revenue generation, sales volume, sales revenue, manufacturing cost, individual growth rate, and other financial ratios.

Prominent Key Players Covered in the report:

Illumina, Inc., Epigentek Group Inc, CD Genomics., Thermo Fisher Scientific, Inc., Novogene Co., Ltd., PerkinElmer, Inc., Promega Corporation

Key Pointers Covered in the Whole Genome Bisulfite Sequencing (WGBS) Market Industry Trends and Forecast

TheWhole Genome Bisulfite Sequencing (WGBS) marketreport provides successfully marked contemplated policy changes, favorable circumstances, industry news, developments, and trends. This information can help readers fortify their market position. It packs various parts of information gathered from secondary sources, including press releases, web, magazines, and journals as numbers, tables, pie-charts, and graphs. The information is verified and validated through primary interviews and questionnaires. The data on growth and trends focuses on new technologies, market capacities, raw materials, CAPEX cycle, and the dynamic structure of the Whole Genome Bisulfite Sequencing (WGBS) market.

Major Regions as Follows:

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The report includes accurately drawn facts and figures, along with graphical representations of vital market data. The research report sheds light on the emerging market segments and significant factors influencing the growth of the industry to help investors capitalize on the existing growth opportunities.

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Table Of Contents: Whole Genome Bisulfite Sequencing (WGBS) Market

Part 01:Executive Summary

Part 02:Scope of the Report

Part 03:Research Methodology

Part 04:Market Landscape

Part 05:Pipeline Analysis

Part 06:Market Sizing

Part 07:Five Forces Analysis

Part 08:Market Segmentation

Part 09:Customer Landscape

Part 10:Regional Landscape

Part 11:Decision Framework

Part 12:Drivers and Challenges

Part 13:Market Trends

Part 14:Vendor Landscape

Part 15:Vendor Analysis

Part 16:Appendix

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To summarize:

The global Whole Genome Bisulfite Sequencing (WGBS) market report studies the contemporary market to forecast the growth prospects, challenges, opportunities, risks, threats, and the trends observed in the market that can either propel or curtail the growth rate of the industry. The market factors impacting the global sector also include provincial trade policies, international trade disputes, entry barriers, and other regulatory restrictions.

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Whole Genome Bisulfite Sequencing (WGBS) Market Expected to Witness High Growth over the Forecast to 2027 KSU | The Sentinel Newspaper - KSU | The...

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Instruction

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WEEKENDS AT THE SCIENCE CENTER: Genome in Me exhibit - WFSB

The cyclin pathway may confer resistance to standard treatments but also offer novel therapeutic opportunities in prostate cancer. In this article, we analyzed prostate cancer samples (majority metastatic) using comprehensive genomic profiling performed by next-generation sequencing (315 genes, >500 coverage) for alterations in activating and sensitizing cyclin genes (CDK4 amplification, CDK6 amplification, CCND1, CCND2, CCND3, CDKN2B [loss], CDKN2A [loss], SMARCB1), androgen receptor (AR) gene, and coalterations in genes leading to cyclin inhibitor therapeutic resistance (RB1 and CCNE1). Overall, cyclin sensitizing pathway genomic abnormalities were found in 9.7% of the 5,356 tumors. Frequent alterations included CCND1 amplification (4.2%) and CDKN2A and B loss (2.4% each). Alterations in possible resistance genes, RB1 and CCNE1, were detected in 9.7% (up to 54.6% in neuroendocrine) and 1.2% of cases, respectively, whereas AR alterations were seen in 20.9% of tumors (~27.3% in anaplastic). Cyclin sensitizing alterations were also more frequently associated with concomitant AR alterations.

The oncologist. 2021 Feb 01 [Epub ahead of print]

DenisL Jardim, Sherri Z Millis, Jeffrey S Ross, Michelle Sue-Ann Woo, Siraj M Ali, Razelle Kurzrock

Department of Clinical Oncology, Hospital Sirio Libanes, So Paulo, Brazil., Foundation Medicine, Cambridge, Massachusetts, USA., Center for Personalized Cancer Therapy and Division of Hematology and Oncology, University of California, San Diego, California, USA.

PubMed http://www.ncbi.nlm.nih.gov/pubmed/33522043

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Landscape of Cyclin Pathway Genomic Alterations Across 5,356 Prostate Cancers: Implications for Targeted Th... - UroToday

New Delhi: Researchers from Peter the Great St. Petersburg Polytechnic University (SPbPU) in collaboration with colleagues from Belgium take a step in the development of genome editing technology. Currently it is possible to deliver genetic material of different sizes and structures to organs and tissues. This is the key to eliminating DNA defects and treating more patients. The project is guided by Professor Gleb Sukhorukov and supported by the Russian Science Foundation. Research results were published in Particle & Particle Systems Characterization journal.An international research group developed a polymer carrier with a number of unique properties, several types of genetic material can be loaded in its structure. In particular, the scientists managed to load genetic material of various sizes and structures into universal containers. From small interfering RNAs (siRNAs) to messenger RNAs (mRNAs). The efficiency of delivery was demonstrated on human stem cells.Nowadays most of the vaccines, including those for COVID-19, are made on the basis of mRNA. This is a kind of genetic SD-card with information which activates human immune system, thus teaches it how to deal with the enemy proteins of the virus. Typically, for medical purposes, different types of carriers are used to deliver specific molecules, we proved that it is possible to deliver genetic materials of different sizes using one type of carrier. This technology opens up new horizons for the development of non-viral delivery systems, notes Alexander Timin, head of the Laboratory for microencapsulation and controlled delivery of biologically active compounds at St. Petersburg Polytechnic University.Scientists added that the micron-scaled carrier with incorporated genetic material can be delivered by systemic administration, or locally (directly into the tumor focus for cancer).The study is conducted jointly with the Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation, which provided the patientsmesenchymal stem cells (cells building organs and tissues) for the experiments. In the future, we plan to conduct experiments on tumor-bearing laboratory animals in order to find out how the genetic material delivered to the tumor will be managed, - said Igor Radchenko, director of the RASA-Polytech center.The Raisa Gorbacheva Memorial Research Institute of Children Oncology, Hematology and Transplantation is interested in the early implementation of these developments in order to fulfill the recommendations and medical protocols that will be introduced into medical practice.

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Genetic SD-card: Scientists obtained new methods to improve the genome editing system - India Education Diary