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Archive for the ‘Biological Engineering’ Category

Genomic data can predict miscarriage and IVF failure

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Infertility is a major reproductive health issue that affects about 12% of women of reproductive age in the United States. Aneuploidy in eggs accounts for a significant proportion of early miscarriage and in vitro fertilization failure. Recent studies have shown that genetic variants in several genes affect chromosome segregation fidelity and predispose women to a higher incidence of egg aneuploidy. However, the exact genetic causes of aneuploid egg production remain unclear, making it difficult to diagnose infertility based on individual genetic variants in mother’s genome. Although, age is a predictive factor for aneuploidy, it is not a highly accurate gauge because aneuploidy rates within individuals of the same age can vary dramatically.

Researchers described a technique combining genomic sequencing with machine-learning methods to predict the possibility a woman will undergo a miscarriage because of egg aneuploidy—a term describing a human egg with an abnormal number of chromosomes. The scientists were able to examine genetic samples of patients using a technique called “whole exome sequencing,” which allowed researchers to home in on the protein coding sections of the vast human genome. Then they created software using machine learning, an aspect of artificial intelligence in which programs can learn and make predictions without following specific instructions. To do so, the researchers developed algorithms and statistical models that analyzed and drew inferences from patterns in the genetic data.

As a result, the scientists were able to create a specific risk score based on a woman’s genome. The scientists also identified three genes—MCM5, FGGY and DDX60L—that when mutated and are highly associated with a risk of producing eggs with aneuploidy. So, the report demonstrated that sequencing data can be mined to predict patients’ aneuploidy risk thus improving clinical diagnosis. The candidate genes and pathways that were identified in the present study are promising targets for future aneuploidy studies. Identifying genetic variations with more predictive power will serve women and their treating clinicians with better information.

References:

https://medicalxpress-com.cdn.ampproject.org/c/s/medicalxpress.com/news/2022-06-miscarriage-failure-vitro-fertilization-genomic.amp

https://pubmed.ncbi.nlm.nih.gov/35347416/

https://pubmed.ncbi.nlm.nih.gov/31552087/

https://pubmed.ncbi.nlm.nih.gov/33193747/

https://pubmed.ncbi.nlm.nih.gov/33197264/

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Reporter and Curator: Dr. Sudipta Saha, Ph.D.

Infertility has been primarily treated as a female predicament but around one-half of infertility cases can be tracked to male factors. Clinically, male infertility is typically determined using measures of semen quality recommended by World Health Organization (WHO). A major limitation, however, is that standard semen analyses are relatively poor predictors of reproductive capacity and success. Despite major advances in understanding the molecular and cellular functions in sperm over the last several decades, semen analyses remain the primary method to assess male fecundity and fertility.

Chronological age is a significant determinant of human fecundity and fertility. The disease burden of infertility is likely to continue to rise as parental age at the time of conception has been steadily increasing. While the emphasis has been on the effects of advanced maternal age on adverse reproductive and offspring health, new evidence suggests that, irrespective of maternal age, higher male age contributes to longer time-to-conception, poor pregnancy outcomes and adverse health of the offspring in later life. The effect of chronological age on the genomic landscape of DNA methylation is profound and likely occurs through the accumulation of maintenance errors of DNA methylation over the lifespan, which have been originally described as epigenetic drift.

In recent years, the strong relation between age and DNA methylation profiles has enabled the development of statistical models to estimate biological age in most somatic tissue via different epigenetic ‘clock’ metrics, such as DNA methylation age and epigenetic age acceleration, which describe the degree to which predicted biological age deviates from chronological age. In turn, these epigenetic clock metrics have emerged as novel biomarkers of a host of phenotypes such as allergy and asthma in children, early menopause, increased incidence of cancer types and cardiovascular-related diseases, frailty and cognitive decline in adults. They also display good predictive ability for cancer, cardiovascular and all-cause mortality.

Epigenetic clock metrics are powerful tools to better understand the aging process in somatic tissue as well as their associations with adverse disease outcomes and mortality. Only a few studies have constructed epigenetic clocks specific to male germ cells and only one study reported that smokers trended toward an increased epigenetic age compared to non-smokers. These results indicate that sperm epigenetic clocks hold promise as a novel biomarker for reproductive health and/or environmental exposures. However, the relation between sperm epigenetic clocks and reproductive outcomes has not been examined.

There is a critical need for new measures of male fecundity for assessing overall reproductive success among couples in the general population. Data shows that sperm epigenetic clocks may fulfill this need as a novel biomarker that predicts pregnancy success among couples not seeking fertility treatment. Such a summary measure of sperm biological age is of clinical importance as it allows couples in the general population to realize their probability of achieving pregnancy during natural intercourse, thereby informing and expediting potential infertility treatment decisions. With the ability to customize high throughput DNA methylation arrays and capture sequencing approaches, the integration of the epigenetic clocks as part of standard clinical care can enhance our understanding of idiopathic infertility and the paternal contribution to reproductive success and offspring health.

References:

https://academic.oup.com/humrep/advance-article/doi/10.1093/humrep/deac084/6583111?login=false

https://pubmed.ncbi.nlm.nih.gov/33317634/

https://clinicalepigeneticsjournal.biomedcentral.com/articles/10.1186/s13148-019-0656-7

https://pubmed.ncbi.nlm.nih.gov/19319879/

https://pubmed.ncbi.nlm.nih.gov/31901222/

https://pubmed.ncbi.nlm.nih.gov/25928123/

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Embryogenesis in Mechanical Womb

Reporter and Curator: Dr. Sudipta Saha, Ph.D.

A highly effective platforms for the ex utero culture of post-implantation mouse embryos have been developed in the present study by scientists of the Weizmann Institute of Science in Israel. The study was published in the journal Nature. They have grown more than 1,000 embryos in this way. This study enables the appropriate development of embryos from before gastrulation (embryonic day (E) 5.5) until the hindlimb formation stage (E11). Late gastrulating embryos (E7.5) are grown in three-dimensional rotating bottles, whereas extended culture from pre-gastrulation stages (E5.5 or E6.5) requires a combination of static and rotating bottle culture platforms.

At Day 11 of development more than halfway through a mouse pregnancy the researchers compared them to those developing in the uteruses of living mice and were found to be identical. Histological, molecular and single-cell RNA sequencing analyses confirm that the ex utero cultured embryos recapitulate in utero development precisely. The mouse embryos looked perfectly normal. All their organs developed as expected, along with their limbs and circulatory and nervous systems. Their tiny hearts were beating at a normal 170 beats per minute. But, the lab-grown embryos becomes too large to survive without a blood supply. They had a placenta and a yolk sack, but the nutrient solution that fed them through diffusion was no longer sufficient. So, a suitable mechanism for blood supply is required to be developed.

Till date the only way to study the development of tissues and organs is to turn to species like worms, frogs and flies that do not need a uterus, or to remove embryos from the uteruses of experimental animals at varying times, providing glimpses of development more like in snapshots than in live videos. This research will help scientists understand how mammals develop and how gene mutations, nutrients and environmental conditions may affect the fetus. This will allow researchers to mechanistically interrogate post-implantation morphogenesis and artificial embryogenesis in mammals. In the future it may be possible to develop a human embryo from fertilization to birth entirely outside the uterus. But the work may one day raise profound questions about whether other animals, even humans, should or could be cultured outside a living womb.

References:

https://www.nature.com/articles/s41586-021-03416-3

https://www.sciencedirect.com/science/article/pii/S0092867414000750?via%3Dihub

https://onlinelibrary.wiley.com/doi/abs/10.1111/j.1469-185X.1978.tb00993.x

https://www.nature.com/articles/199297a0

https://rep.bioscientifica.com/view/journals/rep/35/1/jrf_35_1_018.xml

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National Resilience, Inc. is a first-of-its-kind manufacturing and technology company dedicated to broadening access to complex medicines and protecting biopharmaceutical supply chains against disruption – the Acquisition of Two Premier Biologics Manufacturing Facilities: Boston and in Ontario, Canada

 

Reporter: Aviva Lev-Ari, PhD, RN

Resilience’s new facility, located at 500 Soldiers Field Rd., Boston, MA. (Photo: Business Wire) – The Genzyme-Sanofi Building

 

SAN DIEGO & BOSTON–(BUSINESS WIRE)–Resilience (National Resilience, Inc.), a new company building the world’s most advanced biopharmaceutical manufacturing ecosystem, announced it has acquired two premier commercial manufacturing facilities in North America, joining other facilities already in Resilience’s network to boost total capacity under management to more than 750,000 square feet.

“These locations will serve as hubs for the future of biopharma manufacturing, leading the way and shaping the future of Resilience.”

  • The acquired facilities include a 310,000-square-foot plant in Boston, MA, purchased from Sanofi; and in a separate transaction,
  • a 136,000-square-foot plant in Mississauga, Ontario, Canada.

Both facilities, which currently produce commercial, marketed products, will see significant investments as Resilience adds capacity and capabilities to produce new therapies at these locations. In addition, the company has offered employment to the existing plant staff and intends to add more jobs at each facility.

“We have big plans for these facilities including investing in new capacity, applying new manufacturing technologies, creating jobs and bringing in new customers,” said Rahul Singhvi, Sc.D, Chief Executive Officer of Resilience. “These locations will serve as hubs for the future of biopharma manufacturing, leading the way and shaping the future of Resilience.”

As part of its agreement with Sanofi, Resilience will continue to manufacture a marketed product at the Boston location. The facility plan includes a build out to facilitate multi-modality manufacturing and state-of-the-art quality laboratories to ensure safe, reliable supply to patients. The facility itself is certified ISO 14001 (Environmental management system), OSHAS 18001 (Health & safety management system) and ISO 50001 (Energy management system).​

This is currently the largest of several facilities in Resilience’s growing biologics and advanced therapeutics manufacturing network, with plans to acquire and develop other sites in the U.S. this year. The facility offers 24/7/365 production, multiple 2000L bioreactors capacity and multiple downstream processing trains, with investment in additional capabilities to come.

Our state-of-the-art flexible facility in Mississauga, Ontario, provides upstream, downstream and aseptic fill finish, and is designed to comply with cGMP. The plant has been inspected and approved by multiple regulatory bodies, and handles development and commercialized products.

About Resilience

Resilience (National Resilience, Inc.) is a first-of-its-kind manufacturing and technology company dedicated to broadening access to complex medicines and protecting biopharmaceutical supply chains against disruption. Founded in 2020, the company is building a sustainable network of high-tech, end-to-end manufacturing solutions to ensure the medicines of today and tomorrow can be made quickly, safely, and at scale. Resilience offers the highest quality and regulatory capabilities, and flexible and adaptive facilities to serve partners of all sizes. By continuously advancing the science of biopharmaceutical manufacturing and development, Resilience frees partners to focus on the discoveries that improve patients’ lives.

For more information, visit www.Resilience.com.

Contacts

Ryan Flinn
Head of Communications
Ryan.flinn@Resilience.com
510-207-7616

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Reporter: Stephen J. Williams, PhD

In an announcement televised on C-Span, President Elect Joseph Biden announced his new Science Team to advise on science policy matters, as part of the White House Advisory Committee on Science and Technology. Below is a video clip and the transcript, also available at

https://www.c-span.org/video/?508044-1/president-elect-biden-introduces-white-house-science-team

 

 

COMING UP TONIGHT ON C-SPAN, NEXT, PRESIDENT-ELECT JOE BIDEN AND VICE PRESIDENT-ELECT KAMALA HARRIS ANNOUNCE SEVERAL MEMBERS OF THEIR WHITE HOUSE SCIENCE TEAM. AND THEN SENATE MINORITY LEADER CHUCK SCHUMER TALKS ABOUT THE IMPEACHMENT OF PRESIDENT TRUMP IN THE WEEKLY DEMOCRATIC ADDRESS. AND AFTER THAT, TODAY’S SPEECH BY VICE PRESIDENT MIKE PENCE TO SAILORS AT NAVAL AIR STATION LAMORE IN CALIFORNIA. NEXT, PRESIDENT-ELECT JOE BIDEN AND VICE PRESIDENT-ELECT KAMALA HARRIS ANNOUNCE SEVERAL MEMBERS OF THEIR WHITE HOUSE SCIENCE TEAM. FROM WILMINGTON, DELAWARE, THIS IS ABOUT 40 MINUTES. PRESIDENT-ELECT BIDEN: GOOD AFTERNOON, FOLKS. I WAS TELLING THESE FOUR BRILLIANT SCIENTISTS AS I STOOD IN THE BACK, IN A WAY, THEY — THIS IS THE MOST EXCITING ANNOUNCEMENT THAT I’VE GOTTEN TO MAKE IN THE ENTIRE CABINET RAISED TO A CABINET LEVEL POSITION IN ONE CASE. THESE ARE AMONG THE BRIGHTEST MOST DEDICATED PEOPLE NOT ONLY IN THE COUNTRY BUT THE WORLD. THEY’RE COMPOSED OF SOME OF THE MOST SCIENTIFIC BRILLIANT MINDS IN THE WORLD. WHEN I WAS VICE PRESIDENT AS — I I HAD INTENSE INTEREST IN EVERYTHING THEY WERE DOING AND I PAID ENORMOUS ATTENTION. AND I WOULD — LIKE A KID GOING BACK TO SCHOOL. SIT DOWN AND CAN YOU EXPLAIN TO ME AND THEY WERE — VERY PATIENT WITH ME. AND — BUT AS PRESIDENT, I WANTED YOU TO KNOW I’M GOING TO PAY A GREAT DEAL OF ATTENTION. WHEN I TRAVEL THE WORLD AS VICE PRESIDENT, I WAS OFTEN ASKED TO EXPLAIN TO WORLD LEADERS, THEY ASKED ME THINGS LIKE DEFINE AMERICA. TELL ME HOW CAN YOU DEFINE AMERICA? WHAT’S AMERICA? AND I WAS ON A TIBETAN PLATEAU WITH AT THE TIME WITH XI ZIN PING AND WE HAD AN INTERPRETER CAN I DEFINE AMERICA FOR HIM? I SAID YES, I CAN. IN ONE WORD. POSSIBILITIES. POSSIBILITIES. I THINK IT’S ONE OF THE REASONS WHY WE’VE OCCASIONALLY BEEN REFERRED TO AS UGLY AMERICANS. WE THINK ANYTHING’S POSSIBLE GIVEN THE CHANCE, WE CAN DO ANYTHING. AND THAT’S PART OF I THINK THE AMERICAN SPIRIT. AND WHAT THE PEOPLE ON THIS STAGE AND THE DEPARTMENTS THEY WILL LEAD REPRESENT ENORMOUS POSSIBILITIES. THEY’RE THE ONES ASKING THE MOST AMERICAN OF QUESTIONS, WHAT NEXT? WHAT NEXT? NEVER SATISFIED, WHAT’S NEXT? AND WHAT’S NEXT IS BIG AND BREATHTAKING. HOW CAN — HOW CAN WE MAKE THE IMPOSSIBLE POSSIBLE? AND THEY WERE JUST ASKING QUESTIONS FOR THE SAKE OF QUESTIONS, THEY’RE ASKING THESE QUESTIONS AS CALL TO ACTION. , TO INSPIRE, TO HELP US IMAGINE THE FUTURE AND FIGURE OUT HOW TO MAKE IT REAL AND IMPROVE THE LIVES OF THE AMERICAN PEOPLE AND PEOPLE AROUND THE WORLD. THIS IS A TEAM THAT ASKED US TO IMAGINE EVERY HOME IN AMERICA BEING POWERED BY RENEWABLE ENERGY WITHIN THE NEXT 10 YEARS. OR 3-D IMAGE PRINTERS RESTORING TISSUE AFTER TRAUMATIC INJURIES AND HOSPITALS PRINTING ORGANS FOR ORGAN TRANSPLANTS. IMAGINE, IMAGINE. AND THEY REALLY — AND, YOU KNOW, THEN RALLY, THE SCIENTIFIC COMMUNITY TO GO ABOUT DOING WHAT WE’RE IMAGINING. YOU NEED SCIENCE, DATA AND DISCOVERY WAS A GOVERNING PHILOSOPHY IN THE OBAMA-BIDEN ADMINISTRATION. AND EVERYTHING FROM THE ECONOMY TO THE ENVIRONMENT TO CRIMINAL JUSTICE REFORM AND TO NATIONAL SECURITY. AND ON HEALTH CARE. FOR EXAMPLE, A BELIEF IN SCIENCE LED OUR EFFORTS TO MAP THE HUMAN BRAIN AND TO DEVELOP MORE PRECISE INDIVIDUALIZED MEDICINES. IT LED TO OUR ONGOING MISSION TO END CANCER AS WE KNOW IT, SOMETHING THAT IS DEEPLY PERSONAL TO BOTH MY FAMILY AND KAMALA’S FAMILY AND COUNTLESS FAMILIES IN AMERICA. WHEN PRESIDENT OBAMA ASKED ME TO LEAD THE CANCER MOON SHOT, I KNEW WE HAD TO INJECT A SENSE OF URGENCY INTO THE FIGHT. WE BELIEVED WE COULD DOUBLE THE RATE OF PROGRESS AND DO IN FIVE YEARS WHAT OTHERWISE WOULD TAKE 10. MY WIFE, JILL, AND I TRAVELED AROUND THE COUNTRY AND THE WORLD MEETING WITH THOUSANDS OF CANCER PATIENTS AND THEIR FAMILIES, PHYSICIANS, RESEARCHERS, PHILANTHROPISTS, TECHNOLOGY LEADERS AND HEADS OF STATE. WE SOUGHT TO BETTER UNDERSTAND AND BREAK DOWN THE SILOS AND STOVE PIPES THAT PREVENT THE SHARING OF INFORMATION AND IMPEDE ADVANCES IN CANCER RESEARCH AND TREATMENT WHILE BUILDING A FOCUSED AND COORDINATED EFFORT HERE AT HOME AND ABROAD. WE MADE PROGRESS. BUT THERE’S SO MUCH MORE THAT WE CAN DO. WHEN I ANNOUNCED THAT I WOULD NOT RUN IN 2015 AT THE TIME, I SAID I ONLY HAD ONE REGRET IN THE ROSE GARDEN AND IF I HAD ANY REGRETS THAT I HAD WON, THAT I WOULDN’T GET TO BE THE PRESIDENT TO PRESIDE OVER CANCER AS WE KNOW IT. WELL, AS GOD WILLING, AND ON THE 20TH OF THIS MONTH IN A COUPLE OF DAYS AS PRESIDENT I’M GOING TO DO EVERYTHING I CAN TO GET THAT DONE. I’M GOING TO — GOING TO BE A PRIORITY FOR ME AND FOR KAMALA AND IT’S A SIGNATURE ISSUE FOR JILL AS FIRST LADY. WE KNOW THE SCIENCE IS DISCOVERY AND NOT FICTION. AND IT’S ALSO ABOUT HOPE. AND THAT’S AMERICA. IT’S IN THE D.N.A. OF THIS COUNTRY, HOPE. WE’RE ON THE CUSP OF SOME OF THE MOST REMARKABLE BREAKTHROUGHS THAT WILL FUNDAMENTALLY CHANGE THE WAY OF LIFE FOR ALL LIFE ON THIS PLANET. WE CAN MAKE MORE PROGRESS IN THE NEXT 10 YEARS, I PREDICT, THAN WE’VE MADE IN THE LAST 50 YEARS. AND EXPONENTIAL MOVEMENT. WE CAN ALSO FACE SOME OF THE MOST DIRE CRISES IN A GENERATION WHERE SCIENCE IS CRITICAL TO WHETHER OR NOT WE MEET THE MOMENT OF PERIL AND PROMISE THAT WE KNOW IS WITHIN OUR REACH. IN 1944, FRANKLIN ROOSEVELT ASKED HIS SCIENCE ADVISOR HOW COULD THE UNITED STATES FURTHER ADVANCE SCIENTIFIC RESEARCH IN THE CRITICAL YEARS FOLLOWING THE SECOND WORLD WAR? THE RESPONSE LED TO SOME OF THE MOST GROUND BREAKING DISCOVERIES IN THE LAST 75 YEARS. AND WE CAN DO THAT AGAIN. AND WE CAN DO MORE. SO TODAY, I’M PROUD TO ANNOUNCE A TEAM OF SOME OF THE COUNTRY’S MOST BRILLIANT AND ACCOMPLISHED SCIENTISTS TO LEAD THE WAY. AND I’M ASKING THEM TO FOCUS ON FIVE KEY AREAS. FIRST THE PANDEMIC AND WHAT WE CAN LEARN ABOUT WHAT IS POSSIBLE OR WHAT SHOULD BE POSSIBLE TO ADDRESS THE WIDEST RANGE OF PUBLIC HEALTH NEEDS. SECONDLY, THE ECONOMY, HOW CAN WE BUILD BACK BETTER TO ENSURE PROSPERITY IS FULLY SHARED ALL ACROSS AMERICA? AMONG ALL AMERICANS? AND THIRDLY, HOW SCIENCE HELPS US CONFRONT THIS CLIMATE CRISIS WE FACE IN AMERICA AND THE WORLD BUT IN AMERICA HOW IT HELPS US CONFRONT THE CLIMATE CRISIS WITH AMERICAN JOBS AND INGENUITY. AND FOURTH, HOW CAN WE ENSURE THE UNITED STATES LEADS THE WORLD IN TECHNOLOGIES AND THE INDUSTRIES THAT THE FUTURE THAT WILL BE CRITICAL FOR OUR ECONOMIC PROSPERITY AND NATIONAL SECURITY? ESPECIALLY WITH THE INTENSE INCREASED COMPETITION AROUND THE WORLD FROM CHINA ON? AND FIFTH, HOW CAN WE ASSURE THE LONG-TERM HEALTH AND TRUST IN SCIENCE AND TECHNOLOGY IN OUR NATION? YOU KNOW, THESE ARE EACH QUESTIONS THAT CALL FOR ACTION. AND I’M HONORED TO ANNOUNCE A TEAM THAT IS ANSWERING THE CALL TO SERVE. AS THE PRESIDENTIAL SCIENCE ADVISOR AND DIRECTOR OF THE OFFICE OF SCIENCE AND TECHNOLOGY POLICY, I NOMINATE ONE OF THE MOST BRILLIANT GUYS I KNOW, PERSONS I KNOW, DR. ERIC LANDER. AND THANK YOU, DOC, FOR COMING BACK. THE PIONEER — HE’S A PIONEER IN THE STIFFING COMMUNITY. PRINCIPAL LEADER IN THE HUMAN GENOME PROJECT. AND NOT HYPERBOLE TO SUGGEST THAT DR. LANDER’S WORK HAS CHANGED THE COURSE OF HUMAN HISTORY. HIS ROLE IN HELPING US MAP THE GENOME PULLED BACK THE CURTAIN ON HUMAN DISEASE, ALLOWING SCIENTISTS, EVER SINCE, AND FOR GENERATIONS TO COME TO EXPLORE THE MOLECULAR BASIS FOR SOME OF THE MOST DEVASTATING ILLNESSES AFFECTING OUR WORLD. AND THE APPLICATION OF HIS PIONEERING WORK AS — ARE POISED TO LEAD TO INCREDIBLE CURES AND BREAKTHROUGHS IN THE YEARS TO COME. DR. LANDER NOW SERVES AS THE PRESIDENT AND FOUNDING DIRECTOR OF THE BRODE INSTITUTE AT M.I.T. AND HARVARD, THE WORLD’S FOREMOST NONPROFIT GENETIC RESEARCH ORGANIZATION. AND I CAME TO APPRECIATE DR. LANDER’S EXTRAORDINARY MIND WHEN HE SERVED AS THE CO-CHAIR OF THE PRESIDENT’S COUNCIL ON ADVISORS AND SCIENCE AND TECHNOLOGY DURING THE OBAMA-BIDEN ADMINISTRATION. AND I’M GRATEFUL, I’M GRATEFUL THAT WE CAN WORK TOGETHER AGAIN. I’VE ALWAYS SAID THAT BIDEN-HARRIS ADMINISTRATION WILL ALSO LEAD AND WE’RE GOING TO LEAD WITH SCIENCE AND TRUTH. WE BELIEVE IN BOTH. [LAUGHTER] GOD WILLING OVERCOME THE PANDEMIC AND BUILD OUR COUNTRY BETTER THAN IT WAS BEFORE. AND THAT’S WHY FOR THE FIRST TIME IN HISTORY, I’M GOING TO BE ELEVATING THE PRESIDENTIAL SCIENCE ADVISOR TO A CABINET RANK BECAUSE WE THINK IT’S THAT IMPORTANT. AS DEPUTY DIRECTOR OF THE OFFICE OF SCIENCE AND TECHNOLOGY POLICY AND SCIENCE AND — SCIENCE AND SOCIETY, I APPOINT DR. NELSON. SHE’S A PROFESSOR AT THE INSTITUTE OF ADVANCED STUDIES AT PRINCETON UNIVERSITY. THE PRESIDENT OF THE SOCIAL SCIENCE RESEARCH COUNCIL. AND ONE OF AMERICA’S LEADING SCHOLARS IN THE — AN AWARD-WINNING AUTHOR AND RESEARCHER AND EXPLORING THE CONNECTIONS BETWEEN SCIENCE AND OUR SOCIETY. THE DAUGHTER OF A MILITARY FAMILY, HER DAD SERVED IN THE UNITED STATES NAVY AND HER MOM WAS AN ARMY CRIPPING TO RAFFER. DR. NELSON DEVELOPED A LOVE OF TECHNOLOGY AT A VERY YOUNG AGE PARTICULARLY WITH THE EARLY COMPUTER PRODUCTS. COMPUTING PRODUCTS AND CODE-BREAKING EQUIPMENT THAT EVERY KID HAS AROUND THEIR HOUSE. AND SHE GREW UP WITHIN HER HOME. WHEN I WROTE THAT DOWN, I THOUGHT TO MYSELF, I MEAN, HOW MANY KIDS — ANY WAY, THAT PASSION WAS A PASSION FORGED A LIFELONG CURIOSITY ABOUT THE INEQUITIES AND THE POWER DIAMONDICS THAT SIT BENEATH THE SURFACE OF SCIENTIFIC RESEARCH AND THE TECHNOLOGY WE BUILD. DR. NELSON IS FOCUSED ON THOSE INSIGHTS. AND THE SCIENCE, TECHNOLOGY AND SOCIETY, LIKE FEW BEFORE HER EVER HAVE IN AMERICAN HISTORY. BREAKING NEW GROUND ON OUR UNDERSTANDING OF THE ROLE SCIENCE PLAYS IN AMERICAN LIFE AND OPENING THE DOOR TO — TO A FUTURE WHICH SCIENCE BETTER SERVES ALL PEOPLE. AS CO-CHAIR OF THE PRESIDENT’S COUNCIL ON ADVISORS OF SCIENCE AND TECHNOLOGY,APPOINT DR. FRANCIS ARNOLD, DIRECTOR OF THE ROSE BIOENGINEERING CENTER AT CALTECH AND ONE OF THE WORLD’S LEADING EXPERTS IN PROTEIN ENGINEERING, A LIFE-LONG CHAMPION OF RENEWABLE ENERGY SOLUTIONS WHO HAS BEEN INDUCTED INTO THE NATIONAL INVENTORS’ HALL OF FAME. THAT AIN’T A BAD PLACE TO BE. NOT ONLY IS SHE THE FIRST WOMAN TO BE ELECTED TO ALL THREE NATIONAL ACADEMIES OF SCIENCE, MEDICINE AND ENGINEERING AND ALSO THE FIRST WOMAN, AMERICAN WOMAN, TO WIN A NOBEL PRIZE IN CHEMISTRY. A VERY SLOW LEARNER, SLOW STARTER, THE DAUGHTER OF PITTSBURGH, SHE WORKED AS A CAB DRIVER, A JAZZ CLUB SERVER, BEFORE MAKING HER WAY TO BERKELEY AND A CAREER ON THE LEADING EDGE OF HUMAN DISCOVERY. AND I WANT TO MAKE THAT POINT AGAIN. I WANT — IF ANY OF YOUR CHILDREN ARE WATCHING, LET THEM KNOW YOU CAN DO ANYTHING. THIS COUNTRY CAN DO ANYTHING. ANYTHING AT ALL. AND SO SHE SURVIVED BREAST CANCER, OVERCAME A TRAGIC LOSS IN HER FAMILY WHILE RISING TO THE TOP OF HER FIELD, STILL OVERWHELMINGLY DOMINATED BY MEN. HER PASSION HAS BEEN A STEADFAST COMMITMENT TO RENEWABLE ENERGY FOR THE BETTERMENT OF OUR PLANET AND HUMANKIND. SHE IS AN INSPIRING FIGURE TO SCIENTISTS ACROSS THE FIELD AND ACROSS NATIONS. AND I WANT TO THANK DR. ARNOLD FOR AGREEING TO CO-CHAIR A FIRST ALL WOMAN TEAM TO LEAD THE PRESIDENT’S COUNCIL OF ADVISORS ON SCIENCE AND TECHNOLOGY WHICH LEADS ME TO THE NEXT MEMBER OF THE TEAM. AS CO-CHAIR, THE PRESIDENT’S COUNCIL OF ADVISORS ON SCIENCE AND TECHNOLOGY, I APPOINT DR. MARIE ZUBER. A TRAIL BLAZER BRAISING GEO PHYSICIST AND PLANETARY SCIENTIST A. FORMER CHAIR OF THE NATIONAL SCIENCE BOARD. FIRST WOMAN TO LEAD THE SCIENCE DEPARTMENT AT M.I.T. AND THE FIRST WOMAN TO LEAD NASA’S ROBOTIC PLANETARY MISSION. GROWING UP IN COLE COUNTRY NOT FAR FROM HEAVEN, SCRANTON, PENNSYLVANIA, IN CARBON COUNTY, PENNSYLVANIA, ABOUT 50 MILES SOUTH OF WHERE I WAS A KID, SHE DREAMED OF EXPLORING OUTER SPACE. COULD HAVE TOLD HER SHE WOULD JUST GO TO GREEN REACH IN SCRANTON AND FIND WHERE IT WAS. AND I SHOULDN’T BE SO FLIPPANT. BUT I’M SO EXCITED ABOUT THESE FOLKS. YOU KNOW, READING EVERY BOOK SHE COULD FIND AND LISTENING TO HER MOM’S STORIES ABOUT WATCHING THE EARLIEST ROCKET LAUNCH ON TELEVISION, MARIE BECAME THE FIRST PERSON IN HER FAMILY TO GO TO COLLEGE AND NEVER LET GO OF HER DREAM. TODAY SHE OVERSEES THE LINCOLN LABORATORY AT M.I.T. AND LEADS THE INSTITUTION’S CLIMATE ACTION PLAN. GROWING UP IN COLD COUNTRY, NOT AND FINALLY, COULD NOT BE HERE TODAY, BUT I’M PLEASED TO ANNOUNCE THAT I’VE HAD A LONG CONVERSATION WITH DR. FRANCIS COLLINS AND COULD NOT BE HERE TODAY. AND I’VE ASKED THEM TO STAY ON AS DIRECTOR OF THE INSTITUTE OF HEALTH AND — AT THIS CRITICAL MOMENT. I’VE KNOWN DR. COLLINS FOR MANY YEARS. I WORKED WITH HIM CLOSELY. HE’S BRILLIANT. A PIONEER. A TRUE LEADER. AND ABOVE ALL, HE’S A MODEL OF PUBLIC SERVICE AND I’M HONORED TO BE WORKING WITH HIM AGAIN. AND IT IS — IN HIS ABSENCE I WANT TO THANK HIM AGAIN FOR BEING WILLING TO STAY ON. I KNOW THAT WASN’T HIS ORIGINAL PLAN. BUT WE WORKED AN AWFUL LOT ON THE MOON SHOT AND DEALING WITH CANCER AND I JUST WANT TO THANK HIM AGAIN. AND TO EACH OF YOU AND YOUR FAMILIES, AND I SAY YOUR FAMILIES, THANK YOU FOR THE WILLINGNESS TO SERVE. AND NOT THAT YOU HAVEN’T BEEN SERVING ALREADY BUT TO SERVE IN THE ADMINISTRATION. AND THE AMERICAN PEOPLE, TO ALL THE AMERICAN PEOPLE, THIS IS A TEAM THAT’S GOING TO HELP RESTORE YOUR FAITH IN AMERICA’S PLACE IN THE FRONTIER OF SCIENCE AND DISCOVER AND HOPE. I’M NOW GOING TO TURN THIS OVER STARTING WITH DR. LANDER, TO EACH OF OUR NOMINEES AND THEN WITH — HEAR FROM THE VICE PRESIDENT. BUT AGAIN, JUST CAN’T THANK YOU ENOUGH AND I REALLY MEAN IT. THANK YOU, THANK YOU, THANK YOU FOR WILLING TO DO THIS. DOCTOR, IT’S ALL YOURS. I BETTER PUT MY MASK ON OR I’M GOING TO GET IN TROUBLE.

 

Director’s Page

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Biomolecular Condensates: A new approach to biology originated @MIT – Drug Discovery at DewPoint Therapeutics, Cambridge, MA gets new leaders, Ameet Nathwani, MD (ex-Sanofi, ex-Novartis) as Chief Executive Officer and Arie Belldegrun, PhD (ex-Kite Therapeutics) on R&D

Curator & Reporter: Aviva Lev-Ari, PhD, RN

 

Hooked by the science, Arie Belldegrun joins a group of influentials who believe Dewpoint may have the key to the next big thing in biotech

A new approach to biology

“The real voyage of discovery consists, not in seeking new landscapes, but in having new eyes.” Marcel Proust

Starting with the study of P granules in C.elegans embryos in 2009, Tony Hyman, working with his collaborators like Frank Julicher, Cliff Brangwynne, Simon Alberti, Mike Rosen, and Rohit Pappu, began to unravel the mysteries of biomolecular condensates. These scientists realized that P granules behave like liquid droplets that form by phase separation (think of oil droplets in salad dressing) and called them condensates.

In subsequent studies, they found to their surprise that many compartments inside cells had the behavior of condensates: they are liquid-like and form by phase separation.

Inspired by the work of Tony and his colleagues, Richard Young, Phillip Sharp, and Arup Chakraborty at MIT applied these approaches to the study of gene expression, similarly shedding light on many important questions in gene control.

a video thumbnail

 

Press releases and Dewpoint in the news

 
  • Dewpoint Therapeutics Appoints Ameet Nathwani as Chief Executive Officer

    Dewpoint

  • New York Times interviews Rick Young and Amy Gladfelter on the role of condensate “droplets” in COVID-19

    New York Times

  • Dewpoint Therapeutics raises $77 million to go after ‘undruggable’ diseases

    Boston Globe

  • Hooked by the science, Arie Belldegrun joins a group of influentials who believe Dewpoint may have the key to the next big thing in biotech

    Endpoint News

  • Dewpoint Therapeutics to put ‘pedal to the metal’ with $77M round

    FierceBiotech

  • Dewpoint Therapeutics Raises $77M Series B Financing to Advance the Development of Drugs That Target Biomolecular Condensates

    Dewpoint

  • 21 biotech startups that are set to take off, according to top VCs

    Business Insider

  • Proteins — and labs — coming together to prevent Rett Syndrome

    Whitehead Institute

  • Dewpoint Therapeutics Collaborates with Merck to Evaluate Novel Approach for the Treatment of HIV

    Dewpoint

  • Discovery of how cancer drugs find their targets could lead to a new toolset for drug development

    Whitehead Institute

SOURCE

https://dewpointx.com/news/

Other related article published in this Online Open Access Scientific Journal include: 

Economic Potential of a Drug Invention (Prof. Zelig Eshhar, Weitzman Institute, registered the patent) versus a Cancer Drug in Clinical Trials: CAR-T as a Case in Point, developed by Kite Pharma, under Arie Belldegrun, CEO, acquired by Gilead for $11.9 billion, 8/2017.

https://pharmaceuticalintelligence.com/2017/10/04/economic-potential-of-a-drug-invention-prof-zelig-eshhar-weitzman-institute-registered-the-patent-versus-a-cancer-drug-in-clinical-trials-car-t-as-a-case-in-point-developed-by-kite-pharma-unde/

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UC Berkeley accelerates bio-preservation research as part NSF center

Reporter: Irina Robu, PhD

National Science Foundation funded a new research center which focuses on advancing methods for storing and preserving biological cells and tissues. The new center will be directed by John Bischof at the University of Minnesota  and co-directed by Mehmet Toner at Massachusetts General Hospital in collaboration with researchers from UC Berkeley and UC Riverside. It is known that the inability to extend shelf life of biological tissues means that patients in Florida can’t receive a heart or lung from California. And when thawing any cell culture, the survival rate of the cells are about  60 percent, which is considered normal .

NSF Engineering Research Centers were founded to bring together academic and industry partners in interdisciplinary collaborations to tackle complex, long-range engineering challenges. The anticipation is that the centers will brood whole new industries with new systems-level technologies. In 2025, the award for ATP-Bio may be renewed for an additional five years.

SOURCE

https://engineering.berkeley.edu/news/2020/08/uc-berkeley-part-of-26m-nsf-center-to-accelerate-research-in-bio-preservation/

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Live Notes, Real Time Conference Coverage AACR 2020: Tuesday June 23, 2020 3:00 PM-5:30 PM Educational Sessions

Reporter: Stephen J. Williams, PhD

Follow Live in Real Time using

#AACR20

@pharma_BI

@AACR

Register for FREE at https://www.aacr.org/

uesday, June 23

3:00 PM – 5:00 PM EDT

Virtual Educational Session
Tumor Biology, Bioinformatics and Systems Biology

The Clinical Proteomic Tumor Analysis Consortium: Resources and Data Dissemination

This session will provide information regarding methodologic and computational aspects of proteogenomic analysis of tumor samples, particularly in the context of clinical trials. Availability of comprehensive proteomic and matching genomic data for tumor samples characterized by the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) and The Cancer Genome Atlas (TCGA) program will be described, including data access procedures and informatic tools under development. Recent advances on mass spectrometry-based targeted assays for inclusion in clinical trials will also be discussed.

Amanda G Paulovich, Shankha Satpathy, Meenakshi Anurag, Bing Zhang, Steven A Carr

Methods and tools for comprehensive proteogenomic characterization of bulk tumor to needle core biopsies

Shankha Satpathy
  • TCGA has 11,000 cancers with >20,000 somatic alterations but only 128 proteins as proteomics was still young field
  • CPTAC is NCI proteomic effort
  • Chemical labeling approach now method of choice for quantitative proteomics
  • Looked at ovarian and breast cancers: to measure PTM like phosphorylated the sample preparation is critical

 

Data access and informatics tools for proteogenomics analysis

Bing Zhang
  • Raw and processed data (raw MS data) with linked clinical data can be extracted in CPTAC
  • Python scripts are available for bioinformatic programming

 

Pathways to clinical translation of mass spectrometry-based assays

Meenakshi Anurag

·         Using kinase inhibitor pulldown (KIP) assay to identify unique kinome profiles

·         Found single strand break repair defects in endometrial luminal cases, especially with immune checkpoint prognostic tumors

·         Paper: JNCI 2019 analyzed 20,000 genes correlated with ET resistant in luminal B cases (selected for a list of 30 genes)

·         Validated in METABRIC dataset

·         KIP assay uses magnetic beads to pull out kinases to determine druggable kinases

·         Looked in xenografts and was able to pull out differential kinomes

·         Matched with PDX data so good clinical correlation

·         Were able to detect ESR1 fusion correlated with ER+ tumors

Tuesday, June 23

3:00 PM – 5:00 PM EDT

Virtual Educational Session
Survivorship

Artificial Intelligence and Machine Learning from Research to the Cancer Clinic

The adoption of omic technologies in the cancer clinic is giving rise to an increasing number of large-scale high-dimensional datasets recording multiple aspects of the disease. This creates the need for frameworks for translatable discovery and learning from such data. Like artificial intelligence (AI) and machine learning (ML) for the cancer lab, methods for the clinic need to (i) compare and integrate different data types; (ii) scale with data sizes; (iii) prove interpretable in terms of the known biology and batch effects underlying the data; and (iv) predict previously unknown experimentally verifiable mechanisms. Methods for the clinic, beyond the lab, also need to (v) produce accurate actionable recommendations; (vi) prove relevant to patient populations based upon small cohorts; and (vii) be validated in clinical trials. In this educational session we will present recent studies that demonstrate AI and ML translated to the cancer clinic, from prognosis and diagnosis to therapy.
NOTE: Dr. Fish’s talk is not eligible for CME credit to permit the free flow of information of the commercial interest employee participating.

Ron C. Anafi, Rick L. Stevens, Orly Alter, Guy Fish

Overview of AI approaches in cancer research and patient care

Rick L. Stevens
  • Deep learning is less likely to saturate as data increases
  • Deep learning attempts to learn multiple layers of information
  • The ultimate goal is prediction but this will be the greatest challenge for ML
  • ML models can integrate data validation and cross database validation
  • What limits the performance of cross validation is the internal noise of data (reproducibility)
  • Learning curves: not the more data but more reproducible data is important
  • Neural networks can outperform classical methods
  • Important to measure validation accuracy in training set. Class weighting can assist in development of data set for training set especially for unbalanced data sets

Discovering genome-scale predictors of survival and response to treatment with multi-tensor decompositions

Orly Alter
  • Finding patterns using SVD component analysis. Gene and SVD patterns match 1:1
  • Comparative spectral decompositions can be used for global datasets
  • Validation of CNV data using this strategy
  • Found Ras, Shh and Notch pathways with altered CNV in glioblastoma which correlated with prognosis
  • These predictors was significantly better than independent prognostic indicator like age of diagnosis

 

Identifying targets for cancer chronotherapy with unsupervised machine learning

Ron C. Anafi
  • Many clinicians have noticed that some patients do better when chemo is given at certain times of the day and felt there may be a circadian rhythm or chronotherapeutic effect with respect to side effects or with outcomes
  • ML used to determine if there is indeed this chronotherapy effect or can we use unstructured data to determine molecular rhythms?
  • Found a circadian transcription in human lung
  • Most dataset in cancer from one clinical trial so there might need to be more trials conducted to take into consideration circadian rhythms

Stratifying patients by live-cell biomarkers with random-forest decision trees

Stratifying patients by live-cell biomarkers with random-forest decision trees

Guy Fish CEO Cellanyx Diagnostics

 

Tuesday, June 23

3:00 PM – 5:00 PM EDT

Virtual Educational Session
Tumor Biology, Molecular and Cellular Biology/Genetics, Bioinformatics and Systems Biology, Prevention Research

The Wound Healing that Never Heals: The Tumor Microenvironment (TME) in Cancer Progression

This educational session focuses on the chronic wound healing, fibrosis, and cancer “triad.” It emphasizes the similarities and differences seen in these conditions and attempts to clarify why sustained fibrosis commonly supports tumorigenesis. Importance will be placed on cancer-associated fibroblasts (CAFs), vascularity, extracellular matrix (ECM), and chronic conditions like aging. Dr. Dvorak will provide an historical insight into the triad field focusing on the importance of vascular permeability. Dr. Stewart will explain how chronic inflammatory conditions, such as the aging tumor microenvironment (TME), drive cancer progression. The session will close with a review by Dr. Cukierman of the roles that CAFs and self-produced ECMs play in enabling the signaling reciprocity observed between fibrosis and cancer in solid epithelial cancers, such as pancreatic ductal adenocarcinoma.

Harold F Dvorak, Sheila A Stewart, Edna Cukierman

 

The importance of vascular permeability in tumor stroma generation and wound healing

Harold F Dvorak

Aging in the driver’s seat: Tumor progression and beyond

Sheila A Stewart

Why won’t CAFs stay normal?

Edna Cukierman

 

Tuesday, June 23

3:00 PM – 5:00 PM EDT

 

 

 

 

 

 

 

Other Articles on this Open Access  Online Journal on Cancer Conferences and Conference Coverage in Real Time Include

Press Coverage
Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Symposium: New Drugs on the Horizon Part 3 12:30-1:25 PM
Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on NCI Activities: COVID-19 and Cancer Research 5:20 PM
Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on Evaluating Cancer Genomics from Normal Tissues Through Metastatic Disease 3:50 PM
Live Notes, Real Time Conference Coverage 2020 AACR Virtual Meeting April 28, 2020 Session on Novel Targets and Therapies 2:35 PM

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The Relevance of Glycans in the Viral Pathology of COVID-19

 

Reporter: Ofer Markman, PhD

 

While we are constantly cautioning people from putting too high validity to the results seen in the bellow mentioned Study, 

The ABO blood groups are a result of various and different glycans on the surfaces of red blood cells and their definition is related to Blood Immunology and Blood Typing classification used for Blood Donations. It was the hallmark of the 1930 Nobel prize of medicine.

In the article, ABO blood group glycans modulate sialic acid recognition on erythrocytes the authors claim that the ABH(O) glycan can modulate the surface of cells and their interactions to pathogens, in this case the Malaria pathogen.

Glycans are involved in the interaction of the flu virus to the host cell and the antiviral drug Tamiflu (Oseltamivir ) is based on the inhibition of that sort of interaction/modulation.

The Relevance of Glycans in the Viral Pathology of COVID-19

Even if true, the numbers in this paper show statistical significant difference but mildly significant difference in the risk profile suggesting we are to pay too much attention to the phenomena or worry, regardless of the fact these result have no significance on behavioral instructions nor would call for testing one’s blood type in regards to a viral infection. I would neither totally ignore the finding as it may shed light on viral pathology and infection mechanisms and understanding of the later may lead us to treatment or effective vaccines. But we are still early on this path.

SOURCE

https://www.medrxiv.org/content/10.1101/2020.03.11.20031096v1

Original Reference

Jiao Zhao, Yan Yang, Han-Ping Huang, Dong Li, Dong-Feng Gu, Xiang-Feng Lu, Zheng Zhang, Lei Liu, Ting Liu, Yu-Kun Liu, Yun-Jiao He, Bin Sun, Mei-Lan Wei, Guang-Yu Yang,  View ORCID Profile Xinghuan Wang, Li Zhang, Xiao-Yang Zhou, Ming-Zhao Xing,  View ORCID Profile Peng George Wang

doi: https://doi.org/10.1101/2020.03.11.20031096

yet a more relevant understanding of glycans in the biology of the virus:-

this week NEJM interview shed some more light on the issue in their 2nd part of the talk when they discussed again blood group risk factors in the covid-19 context.

https://www.nejm.org/doi/full/10.1056/NEJMe2023276?query=TOC

Audio Interview: The Challenges of Safe Reopening

List of authors.

  • Eric J. Rubin, M.D., Ph.D., 
  • Lindsey R. Baden, M.D., 
  • and Stephen Morrissey, Ph.D.

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Predicting the Protein Structure of Coronavirus: Inhibition of Nsp15 can slow viral replication and Cryo-EM – Spike protein structure (experimentally verified) vs AI-predicted protein structures (not experimentally verified) of DeepMind (Parent: Google) aka AlphaFold

 

Curators: Stephen J. Williams, PhD and Aviva Lev-Ari, PhD, RN

This illustration, created at the Centers for Disease Control and Prevention (CDC), reveals ultrastructural morphology exhibited by coronaviruses. Note the spikes that adorn the outer surface of the virus, which impart the look of a corona surrounding the virion, when viewed electron microscopically. A novel coronavirus virus was identified as the cause of an outbreak of respiratory illness first detected in Wuhan, China in 2019.

Image and Caption Credit: Alissa Eckert, MS; Dan Higgins, MAM available at https://phil.cdc.gov/Details.aspx?pid=23311

 

UPDATED on 8/9/2020

 

UPDATED on 3/11/2020

Coronaviruses

According to the World Health Organization, coronaviruses make up a large family of viruses named for the crown-like spikes found on their surface (Figure 1). They carry their genetic material in single strands of RNA and cause respiratory problems and fever. Like HIV, coronaviruses can be transmitted between animals and humans.  Coronaviruses have been responsible for the Severe Acute Respiratory Syndrome (SARS) pandemic in the early 2000s and the Middle East Respiratory Syndrome (MERS) outbreak in South Korea in 2015. While the most recent coronavirus, COVID-19, has caused international concern, accessible and inexpensive sequencing is helping us understand COVID-19 and respond to the outbreak quickly.

Figure 1. Coronaviruses with the characteristic spikes as seen under a microscope.

First studies that explore genetic susceptibility to COVID-19 are now being published. The first results indicate that COVID-19 infects cells using the ACE2 cell-surface receptor. Genetic variants in the ACE2 receptor gene are thus likely to influence how effectively COVID-19 can enter the cells in our bodies. Researchers hope to discover genetic variants that confer resistance to a COVID-19 infection, similar to how some variants in the CCR5 receptor gene make people immune to HIV. At Nebula Genomics, we are monitoring the latest COVID-19 research and will add any relevant discoveries to the Nebula Research Library in a timely manner.

The Role of Genomics in Responding to COVID-19

Scientists in China sequenced COVID-19’s genome just a few weeks after the first case was reported in Wuhan. This stands in contrast to SARS, which was discovered in late 2002 but was not sequenced until April of 2003. It is through inexpensive genome-sequencing that many scientists across the globe are learning and sharing information about COVID-19, allowing us to track the evolution of COVID-19 in real-time. Ultimately, sequencing can help remove the fear of the unknown and allow scientists and health professionals to prepare to combat the spread of COVID-19.

Next-generation DNA sequencing technology has enabled us to understand COVID-19 is ~30,000 bases long. Moreover, researchers in China determined that COVID-19 is also almost identical to a coronavirus found in bats and is very similar to SARS. These insights have been critical in aiding in the development of diagnostics and vaccines. For example, the Centers for Disease Control and Prevention developed a diagnostic test to detect COVID-19 RNA from nose or mouth swabs.

Moreover, a number of different government agencies and pharmaceutical companies are in the process of developing COVID-19 vaccines to stop the COVID-19 from infecting more people. To protect humans from infection inactivated virus particles or parts of the virus (e.g. viral proteins) can be injected into humans. The immune system will recognize the inactivated virus as foreign, priming the body to build immunity against possible future infection. Of note, Moderna Inc., the National Institute of Allergy and Infectious Diseases, and Coalition for Epidemic Preparedness Innovations identified a COVID-19 vaccine candidate in a record 42 days. This vaccine will be tested in human clinical trials starting in April.

For more information about COVID-19, please refer to the World Health Organization website.

SOURCE

https://blog.nebula.org/role-of-genomics-coronavirus-covid-19/?utm_source=Nebula%20Genomics&utm_medium=email&utm_campaign=COVID-19

Aviva Lev-Ari
13.3K Tweets

Aviva Lev-Ari
@AVIVA1950

My BIO lnkd.in/eEyn69r MediaPharma ex-SRI ex-MITRE ex-McGraw-Hill Followed by

Aviva Lev-Ari
@AVIVA1950

Predicting the #ProteinStructure of #Coronavirus: #Inhibition of #Nsp15 #Cryo-EM – #spike #protein structure (#experimentally verified) vs #AI-predicted protein structures (not verified) of

(

) #AlphaFold

Quote Tweet
Eric Topol
@EricTopol
·
The problem w/ visionaries is that we don’t recognize them in a timely manner (too late) Ralph Baric @UNCpublichealth and Vineet Menachery deserve recognition for being 5 yrs ahead of #COVID19 nature.com/articles/nm.39 @NatureMedicine pnas.org/content/113/11 @PNASNews via @hoondy

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Senior, A.W., Evans, R., Jumper, J. et al. Improved protein structure prediction using potentials from deep learningNature 577, 706–710 (2020)https://doi.org/10.1038/s41586-019-1923-7

Abstract

Protein structure prediction can be used to determine the three-dimensional shape of a protein from its amino acid sequence1. This problem is of fundamental importance as the structure of a protein largely determines its function2; however, protein structures can be difficult to determine experimentally. Considerable progress has recently been made by leveraging genetic information. It is possible to infer which amino acid residues are in contact by analysing covariation in homologous sequences, which aids in the prediction of protein structures3. Here we show that we can train a neural network to make accurate predictions of the distances between pairs of residues, which convey more information about the structure than contact predictions. Using this information, we construct a potential of mean force4 that can accurately describe the shape of a protein. We find that the resulting potential can be optimized by a simple gradient descent algorithm to generate structures without complex sampling procedures. The resulting system, named AlphaFold, achieves high accuracy, even for sequences with fewer homologous sequences. In the recent Critical Assessment of Protein Structure Prediction5 (CASP13)—a blind assessment of the state of the field—AlphaFold created high-accuracy structures (with template modelling (TM) scores6 of 0.7 or higher) for 24 out of 43 free modelling domains, whereas the next best method, which used sampling and contact information, achieved such accuracy for only 14 out of 43 domains. AlphaFold represents a considerable advance in protein-structure prediction. We expect this increased accuracy to enable insights into the function and malfunction of proteins, especially in cases for which no structures for homologous proteins have been experimentally determined7. https://doi.org/10.1038/s41586-019-1923-7

[ALA added bold face]

COVID-19 outbreak

The scientific community has galvanised in response to the recent COVID-19 outbreak, building on decades of basic research characterising this virus family. Labs at the forefront of the outbreak response shared genomes of the virus in open access databases, which enabled researchers to rapidly develop tests for this novel pathogen. Other labs have shared experimentally-determined and computationally-predicted structures of some of the viral proteins, and still others have shared epidemiological data. We hope to contribute to the scientific effort using the latest version of our AlphaFold system by releasing structure predictions of several under-studied proteins associated with SARS-CoV-2, the virus that causes COVID-19. We emphasise that these structure predictions have not been experimentally verified, but hope they may contribute to the scientific community’s interrogation of how the virus functions, and serve as a hypothesis generation platform for future experimental work in developing therapeutics. We’re indebted to the work of many other labs: this work wouldn’t be possible without the efforts of researchers across the globe who have responded to the COVID-19 outbreak with incredible agility.

Knowing a protein’s structure provides an important resource for understanding how it functions, but experiments to determine the structure can take months or longer, and some prove to be intractable. For this reason, researchers have been developing computational methods to predict protein structure from the amino acid sequence.  In cases where the structure of a similar protein has already been experimentally determined, algorithms based on “template modelling” are able to provide accurate predictions of the protein structure. AlphaFold, our recently published deep learning system, focuses on predicting protein structure accurately when no structures of similar proteins are available, called “free modelling”.  We’ve continued to improve these methods since that publication and want to provide the most useful predictions, so we’re sharing predicted structures for some of the proteins in SARS-CoV-2 generated using our newly-developed methods.

It’s important to note that our structure prediction system is still in development and we can’t be certain of the accuracy of the structures we are providing, although we are confident that the system is more accurate than our earlier CASP13 system. We confirmed that our system provided an accurate prediction for the experimentally determined SARS-CoV-2 spike protein structure shared in the Protein Data Bank, and this gave us confidence that our model predictions on other proteins may be useful. We recently shared our results with several colleagues at the Francis Crick Institute in the UK, including structural biologists and virologists, who encouraged us to release our structures to the general scientific community now. Our models include per-residue confidence scores to help indicate which parts of the structure are more likely to be correct. We have only provided predictions for proteins which lack suitable templates or are otherwise difficult for template modeling.  While these understudied proteins are not the main focus of current therapeutic efforts, they may add to researchers’ understanding of SARS-CoV-2.

Normally we’d wait to publish this work until it had been peer-reviewed for an academic journal. However, given the potential seriousness and time-sensitivity of the situation, we’re releasing the predicted structures as we have them now, under an open license so that anyone can make use of them.

Interested researchers can download the structures here, and can read more technical details about these predictions in a document included with the data. The protein structure predictions we’re releasing are for SARS-CoV-2 membrane protein, protein 3a, Nsp2, Nsp4, Nsp6, and Papain-like proteinase (C terminal domain). To emphasise, these are predicted structures which have not been experimentally verified. Work on the system continues for us, and we hope to share more about it in due course.

Citation:  John Jumper, Kathryn Tunyasuvunakool, Pushmeet Kohli, Demis Hassabis, and the AlphaFold Team, “Computational predictions of protein structures associated with COVID-19”, DeepMind website, 5 March 2020, https://deepmind.com/research/open-source/computational-predictions-of-protein-structures-associated-with-COVID-19

SARS-COV-2 MEMBRANE PROTEIN: A RENDERING OF ONE OF OUR PROTEIN STRUCTURE PREDICTIONS

SOURCES

Computational predictions of protein structures associated with COVID-19

https://deepmind.com/research/open-source/computational-predictions-of-protein-structures-associated-with-COVID-19

AlphaFold: Using AI for scientific discovery 

https://deepmind.com/blog/article/AlphaFold-Using-AI-for-scientific-discovery

 

DeepMind has shared its results with researchers at the Francis Crick Institute, a biomedical research lab in the UK, as well as offering it for download from its website.

“Normally we’d wait to publish this work until it had been peer-reviewed for an academic journal. However, given the potential seriousness and time-sensitivity of the situation, we’re releasing the predicted structures as we have them now, under an open license so that anyone can make use of them,” it said. [ALA added bold face]

There are 93,090 cases of COVID-19, and 3,198 deaths, spread across 76 countries, according to the latest report from the World Health Organization at time of writing. ®

SOURCE

https://www.theregister.co.uk/2020/03/06/deepmind_covid19_outbreak/

 

  • MHC content – The spike protein is thought to be the key to binding to cells via the angiotensin II receptor, the major mechanism the immune system uses to distinguish self from non-self

Preliminary Identification of Potential Vaccine Targets for the COVID-19 Coronavirus (SARS-CoV-2) Based on SARS-CoV Immunological Studies

Syed Faraz Ahmed 1,† , Ahmed A. Quadeer 1, *,† and Matthew R. McKay 1,2, *

1 Department of Electronic and Computer Engineering, The Hong Kong University of Science and

Technology, Hong Kong, China; sfahmed@connect.ust.hk

2 Department of Chemical and Biological Engineering, The Hong Kong University of Science and

Technology, Hong Kong, China

* Correspondence: eeaaquadeer@ust.hk.com (A.A.Q.); m.mckay@ust.hk (M.R.M.)

These authors contributed equally to this work.

Received: 9 February 2020; Accepted: 24 February 2020; Published: 25 February 2020

Abstract:

The beginning of 2020 has seen the emergence of COVID-19 outbreak caused by a novel coronavirus, Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2). There is an imminent need to better understand this new virus and to develop ways to control its spread. In this study, we sought to gain insights for vaccine design against SARS-CoV-2 by considering the high genetic similarity between SARS-CoV-2 and SARS-CoV, which caused the outbreak in 2003, and leveraging existing immunological studies of SARS-CoV. By screening the experimentally determined SARS-CoV-derived B cell and T cell epitopes in the immunogenic structural proteins of SARS-CoV, we identified a set of B cell and T cell epitopes derived from the spike (S) and nucleocapsid (N) proteins that map identically to SARS-CoV-2 proteins. As no mutation has been observed in these identified epitopes among the 120 available SARS-CoV-2 sequences (as of 21 February 2020), immune targeting of these epitopes may potentially offer protection against this novel virus. For the T cell epitopes, we performed a population coverage analysis of the associated MHC alleles and proposed a set of epitopes that is estimated to provide broad coverage globally, as well as in China. Our findings provide a screened set of epitopes that can help guide experimental efforts towards the development of vaccines against SARS-CoV-2.

Keywords: Coronavirus; 2019-nCoV; 2019 novel coronavirus; SARS-CoV-2; COVID-19; SARS-CoV; MERS-CoV; T cell epitopes; B cell epitopes; vaccine [ALA added bold face]

SOURCE

https://www.mdpi.com/1999-4915/12/3/254/pdf

 

Selected Online COMMENTS to

https://forums.theregister.co.uk/forum/all/2020/03/06/deepmind_covid19_outbreak/

MuscleguySilver badge

Re: Protein structure prediction has been done for ages…

Not quite, Natural Selection does not measure methods, it measures outputs, usually at the organism level.

Sure correct folding is necessary for much protein function and we have prions and chaperone proteins to get it wrong and right.

The only way NS measures methods and mechanisms is if they are very energetically wasteful. But there are some very wasteful ones out there. Beta-Catenin at the end of point of Wnt signalling comes particularly to mind.

Chemist

Re: Does not matter at all

“Determining the structure of the virus proteins might also help in developing a molecule that disrupts the operation of just those proteins, and not anything else in the human body.”

Well it might, but predicting whether a ‘drug’ will NOT interact with any other of the 20000+ protein in complex organisms is well beyond current science. If we could do that we could predict/avoid toxicity and other non-mechanism related side-effects & mostly we can’t.

rob miller

Title

There are 480 structures on PDBe resulting from a search on ‘coronavirus,’ the top hits from MERS and SARS. PR stunt or not, they did win the most recent CASP ‘competition’, so arguably it’s probably our best shot right now – and I am certainly not satisfied that they have been sufficiently open in explaining their algorithms though I have not checked in the last few months. No one is betting anyone’s health on this, and it is not like making one wrong turn in a series of car directions. Latest prediction algorithms incorporate contact map predictions, so it’s not like a wrong dihedral angle sends the chain off in the wrong direction. A decent model would give something to run docking algorithms against with a series of already approved drugs, then we take that shortlist into the lab. A confirmed hit could be an instantly available treatment, no two year wait as currently estimated. [ALA added bold face]

jelabarre59Silver badge

Re: these structure predictions have not been experimentally verified

Naaaah. Can’t possibly be a stupid marketing stunt.

Well yes, a good possibility. But it can also be trying to build on the open-source model of putting it out there for others to build and improve upon. Essentially opening that “peer review” to a larger audience quicker. [ALA added bold face]

We shall see.

Anonymous Coward

Anonymous CowardWhat bothers me, besides the obvious PR stunt, is that they say this prediction is licensed. How can a prediction from software be protected by, I presume, patents? And if this can be protected without even verifying which predictions actually work, what’s to stop someone spitting out millions of random, untested predictions just in case they can claim ownership later when one of them is proven to work? [ALA added bold face]

 

 

SOURCES

 

  • AI-predicted protein structures could unlock vaccine for Wuhan coronavirus… if correct… after clinical trials It’s not quite DeepMind’s ‘Come with me if you want to live’ moment, but it’s close, maybe

Experimentally derived by a group of scientists at the University of Texas at Austin and the National Institute of Allergy and Infectious Diseases, an agency under the US National Institute of Health. They both feature a “Spike protein structure.”

  • Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

See all authors and affiliations

Science  19 Feb 2020:
eabb2507
DOI: 10.1126/science.abb2507

 

  • Israeli scientists: We have developed a coronavirus vaccine

https://www.fromthegrapevine.com/health/coronavirus-vaccine-israel-migal-research-institute-david-zigdon

Other related articles published in this Open Access Online Scientific Journal include the following:

 

  • Group of Researchers @ University of California, Riverside, the University of Chicago, the U.S. Department of Energy’s Argonne National Laboratory, and Northwestern University solve COVID-19 Structure and Map Potential Therapeutics

Reporters: Stephen J Williams, PhD and Aviva Lev-Ari, PhD, RN

https://pharmaceuticalintelligence.com/2020/03/06/group-of-researchers-solve-covid-19-structure-and-map-potential-therapeutic/

 

  • Is It Time for the Virtual Scientific Conference?: Coronavirus, Travel Restrictions, Conferences Cancelled Curator:

Stephen J. Williams, PhD

https://pharmaceuticalintelligence.com/2020/03/06/is-it-time-for-the-virtual-scientific-conference-coronavirus-travel-restrictions-conferences-cancelled/

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