Colorado-based Gene-Editing Company gets Series C Financing

Inscripta Completes $20M Expansion of Series C Financing, Increasing Total Round to $105.5M

BOULDER, Colo.--(BUSINESS WIRE)--Inscripta, a leading gene editing technology company, today announced that it has increased its previously announced Series C financing with an additional $20 million from existing investors. The new funding adds to the $85.5 million financing Inscripta announced in 2018, bringing the total raised for the round to $105.5 million.

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8,000 years of human adventure in the Iberian Peninsula

Spotlight on Ancient Iberia

Largest-ever ancient DNA study of region spans 8,000 years 

Stephenie Dutchen, Harvard Medicine News 

The largest study to date of ancient DNA from the Iberian Peninsula (modern-day Portugal and Spain) offers new insights into the populations that lived in this region over the last 8,000 years. The most startling discovery suggests that local Y chromosomes were almost completely replaced during the Bronze Age.

Starting in 2500 B.C. and continuing for about 500 years, the analyses indicate, tumultuous social events played out that reshaped Iberians' paternal ancestry continuing to today.

“This is one of the strongest pieces of evidence in ancient-DNA research of sex bias in the prehistoric period,” said Iñigo Olalde, a postdoctoral fellow in the lab of David Reich at Harvard Medical School and first author of the study.

The work, published online in Science March 15 by a 111-person international team led by researchers at HMS and the Institute of Evolutionary Biology in Barcelona, Spain, also details genetic variation among ancient hunter-gatherers, documents intermingling of ancient Iberians with people from North Africa and the Mediterranean, and provides an additional explanation for why present-day Basques, who have such a distinctive language and culture, are also ancestrally different from other Iberians.

Some of the findings support or clarify what is known about the history and prehistory of Iberia, while others challenge them.

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"Elite" stem cells help dominate the reprogramming niche

Not all stem cells are created equal

Researchers have discovered a population of cells – dubbed to be “elite” – that play a key role in the process of transforming differentiated cells into stem cells. The finding has important implications for regenerative medicine.

Stem cells have the ability to transform into specialized cells – from lung to brain. Stem cells are common in embryos, but within the last 15 years, a technique called cell reprogramming has enabled scientists to turn mature cells back into so-called pluripotent stem cells, with the power to develop into any cell type.

While reprogramming is well understood, less is known about the intricacies of how individual reprogramming cells behave in a population setting. Researchers found a group of cells that appear to have a competitive advantage in reprogramming. The research is published in Science.

The team used cells extracted from mouse skin, known as mouse embryonic fibroblasts (MEFs). They used DNA-barcoding technologies to give each MEF a unique tag, track individual cells during reprogramming and associate them with their parent population. They also used computational modelling to help understand the complex data generated and to make predictions that were tested in the lab.

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Nanopore pioneers ultrafast tumor analyses

Same-day genomic and epigenomic analysis of brain tumors

via GIPHY

A plethora of technologies are currently required to assess different genomic and epigenomic alterations; however, the associated costs and long turnaround times combined with extensive infrastructure and training requirements have, to date, hindered their implementation1 . To address these challenges, Dr. Philippe Euskirchen and co-workers at the ICM Brain and Spine Institute, France, assessed the potential of nanopore sequencing technology to deliver comprehensive and cost-effective characterisation of genetic alterations in brain cancer samples — including analysis of copy number (CN) alterations, epigenetic base modifications, and single nucleotide variations (SNVs)1,2. Furthermore, all nanopore sequencing workflows were designed to go from sample to result within a single day.

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Selective Serotonin reuptake of by Chromatin

Mood-Altering Messenger Goes Nuclear

Francis Collins, NIH Director's Blog

Serotonin is best known for its role as a chemical messenger in the brain, helping to regulate mood, appetite, sleep, and many other functions. It exerts these influences by binding to its receptor on the surface of neural cells. But startling new work suggests the impact of serotonin does not end there: the molecule also can enter a cell’s nucleus and directly switch on genes.

While much more study is needed, this is a potentially groundbreaking discovery. Not only could it have implications for managing depression and other mood disorders, it may also open new avenues for treating substance abuse and neurodegenerative diseases.

To understand how serotonin contributes to switching genes on and off, a lesson on epigenetics is helpful. Keep in mind that the DNA instruction book of all cells is essentially the same, yet the chapters of the book are read in very different ways by cells in different parts of the body. Epigenetics refers to chemical marks on DNA itself or on the protein “spools” called histones that package DNA. These marks influence the activity of genes in a particular cell without changing the underlying DNA sequence, switching them on and off or acting as “volume knobs” to turn the activity of particular genes up or down.

The marks include various chemical groups—including acetyl, phosphate, or methyl—which are added at precise locations to those spool-like proteins called histones. The addition of such groups alters the accessibility of the DNA for copying into messenger RNA and producing needed proteins.

In the study reported in Nature, researchers led by Ian Maze and postdoctoral researcher Lorna Farrelly, Icahn School of Medicine at Mount Sinai, New York, followed a hunch that serotonin molecules might also get added to histones [1]. There had been hints that it might be possible. For instance, earlier evidence suggested that inside cells, serotonin could enter the nucleus. There also was evidence that serotonin could attach to proteins outside the nucleus in a process called serotonylation.

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American Society of Human Genetics to expand Developing Country Awards Program

ASHG Announces Expansion to Developing Country Awards Program
25 Travel Awards Will Enhance Africa’s Participation in Scientific Dialogue

ROCKVILLE, Md. – The American Society of Human Genetics (ASHG), in collaboration with the National Human Genome Research Institute (NHGRI), is pleased to announce the addition of 25 awards to its annual Developing Country Awards Program. The new awards will enable 25 genetics trainees and/or early- to mid-career investigators from Africa who are currently working in Africa to attend the ASHG 2019 Annual Meeting, taking place October 15-19, 2019, in Houston, Texas. They will be supported by NHGRI; the Human, Heredity, and Health in Africa (H3Africa) consortium; and ASHG; and administered via the H3Africa Coordinating Center at the University of Cape Town.

“Through these awards, we hope to enhance the participation and visibility of promising African geneticists at the world’s largest genetics meeting,” said Kiran Musunuru, MD, PhD, 2019 Chair of the ASHG Program Committee. “By working to enrich the diversity of voices engaged in research worldwide, we reaffirm our commitment to global science, and we hope to grow similar partnerships in other regions in the future,” he said.

“In Africa, there is a growing research community using genomic methods in biomedical research to address the substantial disease burden,” explained Jennifer Troyer, PhD, H3Africa Program Director at NHGRI. “Over the past decade, the H3Africa Consortium and other international global health efforts have increased support for research leaders in Africa to address vital research topics there and to provide training for the next generation of African researchers, leading to the growth of genetics and genomics research on the continent,” said Dr. Troyer.

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Birds illustrate how genomics can make things harder, even if it makes things better

What’s in a Name? How Genome Mapping Can Make It Harder to Tell Species Apart

Rebecca Heisman, Living Bird

If you had opened a copy of the Sibley Guide to Birds when it was first published in the year 2000 and flipped to the section on wood-warblers, you would have found 13 pages devoted to members of a single genus: Dendroica, Latin for tree-dweller. Dendroica’s inhabitants included 21 colorful species—such as Magnolia, Blackburnian, and Cerulean Warblers—dear to the hearts of many birders.

Open a copy of the second edition of the Sibley Guide today, and Dendroica is nowhere to be found.

There hasn’t been a mass extinction in the intervening years. The wood-warbler species are all still there, but filed under a different genus name, Setophaga. Instead, there has been a major shift in how ornithologists sort and classify bird species, and the genus name Dendroica was a casualty.

Decisions about how North American bird species are classified and what is and is not considered a species are made every summer by a special committee of the American Ornithological Society. An AOS committee bases its judgments on the best available science. But the science is rapidly expanding. Like many other branches of biology, ornithologists are trying to make sense of a flood of new information flowing from the latest advances in genome mapping. Today, avian geneticists can dive deep into genomes to unveil the molecular differences underlying variation between birds.

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Nat-Geo addresses the idea of a gene

The Gene: Science's Most Powerful—and Dangerous—Idea

SIMON WORRALL, National Geographic

The gene is “one of the most powerful and dangerous ideas in the history of science,” argues Siddhartha Mukherjee in The Gene: An Intimate History . Since its discovery by Gregor Mendel, an obscure Moravian monk, the gene has been both a force for good and ill. In the 1930s, the Nazis exploited the pseudoscience of eugenics as a prelude to the Holocaust. Today, gene therapy holds out the hope of eradicating hereditary conditions like Huntington’s disease and even psychological disturbances, such as schizophrenia. [See how the DNA revolution is giving us unprecedented power.]

National Geographic caught up with the author as he was driving across the Williamsburg Bridge in New York City. Mukherjee, a professor of medicine at Columbia University who also wrote the Pulitzer Prize-winning The Emperor of All Maladies about cancer, explained why the book has deep personal roots, how the United States eagerly adopted the pseudoscience of eugenics, and why allowing individuals to make decisions about altering the genetic makeup of their children may be a dangerous thing to do.

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CliffNotes genome another Synthetic Lifeform

First computer-generated genome could lead to custom synthetic lifeforms

Scientists at ETH Zurich have created the first fully computer-generated genome of a living organism. The brand new genome, named Caulobacter ethensis-2.0, was built by essentially cleaning up and simplifying the natural code of a bacterium called Caulobacter crescentus. For now it exists as one large DNA molecule and not a living organism itself, but the team says this is a huge step towards creating completely synthetic life and medicinal DNA molecules.

Over a decade ago, a team led by geneticist Craig Venter created the first "synthetic" bacterium, which was basically a digital copy of the Mycoplasma mycoides genome. That was then implanted into recipient cells and found to be a viable version of the real creature, even being able to self-replicate.

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Excitement over the Single-Cell Genomics Market

Single-Cell Genomics Market Expected To Reach A Highest Growth During Forecast Period

Single Cell Genomics is a rapidly growing market due to the new emerging methodologies in which the genomic technologies are applied at the single cell level, rather to all the cells collectively. The single cell genomic technologies are opening new boundaries by separating the contributions of single cells to the diversity of ecosystem and organisms. The single cell genomics is also creating new insight into multifaceted biological systems that range from the microbial ecosystem diversity to the human cancer genomics. To mention an example, the single cell genomics can probably be used to identify as well as assemble the genomes of the microorganisms which cannot be cultured, single cell genomics also evaluates the part genetic mosaic plays in the normal physiology and also determines the role of intra tumor genetic variation responsible for cancer development or treatment. However, the single cell genomics has the ability to evaluate a single DNA molecule from single isolated cells, but the process is technically challenging.

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Single-Nucleus RNA Sequencing and its variants

Single-Nucleus RNA Sequencing (sNuc-seq) Applications

By P Surat, Ph.D. Reviewed by Michael Greenwood, M.Sc.

In earlier studies investigating RNA or DNA, all the cells of a population were pooled together to collect information. However, the diversity and complexity of various cell types are becoming increasingly clear. Single nucleus RNA sequencing techniques have been developed to sequence the RNA present in single cells.

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A bioengineer, a biopunk, and a biotech reporter talk about Genetic Engineering

The Future of Genetic Engineering

A bioengineer, a biopunk, and a biotech reporter square off onstage about our neobiological future.

By Jane Metcalfe

In a new documentary that is still in production, filmmaker Cory Sheehy follows renowned bioengineer George Church and biotech reporter Antonio Regalado to China for the 2nd International Summit on Human Genome Editing. That’s where biophysicist He Jiankui made the stunning announcement that he had edited the DNA of two twin girls who were born in November 2018. Back in California, the filmmaker catches up with biohacker Josiah Zayner, whose attention-grabbing exploits—part protest, part performance art—include injecting himself with a CRISPR-Cas9 plasmid.

Watch the video here …

Consumer sequencing startup hope to rival 23andMe

A Silicon Valley startup just launched a DNA-based health test that could be a big competitor to 23andMe

• On Tuesday, DNA testing startup Helix launched a new test that looks at your risk of diseases like breast cancer, colon cancer, and high cholesterol.

• You can buy the test online for $260, but it must be approved by a physician.

• Helix partnered with clinical diagnostics company PerkinElmer to create the test, which includes genetics counseling.

• The test also uses a type of sequencing that some experts say all DNA-based health tests should use.

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Blood tests versus biopsies

Could a simple blood test replace the invasive tissue biopsy?

Answer: It’s complicated …

Jake Siegel / Fred Hutch News Service

For years, the idea seemed as far-fetched as a fairy tale.

Once upon a time, there was a tumor cell that died. It’s innards spilled out into the bloodstream of the body where it had lived. The owner of that body went to a doctor and got a blood draw for a test, which identified the cell’s floating DNA fragments as cancer. The doctor then drew up a personalized treatment plan based on those bits of DNA, and the patient lived happily ever after …

The appeal of a simple blood test to detect and analyze cancer is obvious. It could replace the necessary evil of tissue biopsies — invasive, often risky and painful procedures to collect tumor cells with a needle or through surgery. A vial of blood sounds like a better trade than a chunk of tissue.

Recently, the idea of these so-called “liquid biopsies” seems less like a fantasy. 

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Cleveland Clinic Commentary for Cancer Screening

Personalizing guideline-driven cancer screening

Gautam Mankaney, MD Carol A. Burke, MD, FACG, FACP, FASGE

Cleveland Clinic Journal of Medicine (Commentary)

Reports of cancer date back thousands of years to Egyptian texts. Its existence baffled scientists until the 1950s, when Watson, Crick, and Franklin discovered the structure of DNA, laying the groundwork for identifying the genetic pathways leading to cancer. Currently, cancer is a leading global cause of death and the second leading cause of death in the United States.

In an effort to curtail cancer and its related morbidity and mortality, population-based screening programs have been implemented with tests that identify precancerous lesions and, preferably, early-stage rather than late-stage cancer.

Screening for cancer can lead to early diagnosis and prevent death from cancer, but the topic continues to provoke controversy.

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Gene-Edited Anolis Lizards

UGA scientists create world’s first gene-edited lizards

A group of University of Georgia researchers led by geneticist Douglas Menke has become the first in the world to successfully produce a genetically modified reptile—specifically, four albino lizards—using the CRISPR-Cas9 gene-editing tool. The team’s results, which appeared online March 31, have been submitted for peer review.

“Reptiles are very understudied in terms of their reproductive biology and embryonic development,” said Menke, associate professor in the department of genetics. “There are no good methods to manipulate embryos like we can easily do with mammals, fish or amphibians. To our knowledge, no other lab in the world has produced a genetically altered reptile.”

Gene manipulation using CRISPR typically involves injecting gene-editing solutions into an animal’s newly fertilized egg or single-cell embryo, causing a mutation in the DNA that is reproduced in all subsequent cells. However female reptiles can store sperm in their oviducts for long periods, making it difficult to pinpoint the exact moment of fertilization. Also, the physiology of their fertilized eggs, which have pliable shells with no air space inside, presents challenges for manipulating embryos without damaging them.

Working with the species Anolis sagrei, commonly called the brown anole, Menke’s team overcame these challenges by microinjecting CRISPR proteins into multiple immature eggs, or oocytes, still located in the lizards’ ovaries. Targeting the tyrosinase gene, they successfully injected 146 oocytes from 21 lizards, then waited for the oocytes to be fertilized naturally. Within a few weeks, they realized their goal: four offspring displaying the telltale trait of albinism, which results when tyrosinase is inactivated.

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OncoCell Presents Noninvasive Blood-Based Assay for Prostate Cancer

OncoCell Announces Late-Breaking Poster Presentation at AACR 2019 on a Noninvasive Blood-Based Assay for Prostate Cancer Prognosis

ATLANTA--(BUSINESS WIRE)--Apr 1, 2019--OncoCell MDx, a company developing novel noninvasive diagnostic and prognostic tests, will present results from a feasibility study of a new prostate cancer prognostic assay in a late-breaking poster session at the American Association of Cancer Research (AACR) Annual Meeting tomorrow. The study demonstrates that the blood-based immunogenomics RNA expression assay provides a prognostic summary comparable to that of prostate biopsy.

OncoCell’s Subtraction-Normalized Expression of Phagocytes (SNEP) based platform, invented by Professor Amin Kassis, while at Harvard Medical School, uses a proprietary algorithm to interrogate changes in gene expression of two immune cell types consequent to prostate cancer including phagocytic (CD14) and non-phagocytic (CD2) cells, filters out intrinsic genomic variation not related to the disease, and identifies and validates prostate cancer-specific signatures. A study of blood samples from 713 prostate cancer patients showed the platform provides a prognostic summary including tumor Gleason grade distribution, size/volume and heterogeneity that is comparable to prostate biopsy information, and that it stratifies patients with aggressive disease that need life-saving treatment from those with indolent disease.

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New Genome Assembler Makes Progress on Fundamental Problem

Assembly of long, error-prone reads using repeat graphs

Mikhail Kolmogorov, Jeffrey Yuan, Yu Lin & Pavel A. Pevzner

Nature Biotechnology (Research Article)

Abstract—Accurate genome assembly is hampered by repetitive regions. Although long single molecule sequencing reads are better able to resolve genomic repeats than short-read data, most long-read assembly algorithms do not provide the repeat characterization necessary for producing optimal assemblies. Here, we present Flye, a long-read assembly algorithm that generates arbitrary paths in an unknown repeat graph, called disjointigs, and constructs an accurate repeat graph from these error-riddled disjointigs. We benchmark Flye against five state-of-the-art assemblers and show that it generates better or comparable assemblies, while being an order of magnitude faster. Flye nearly doubled the contiguity of the human genome assembly (as measured by the NGA50 assembly quality metric) compared with existing assemblers

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Small transposable elements can have big effects on genome size

Genome Size Evolution: Small Transposons with Large Consequences

Alexander Suh

Current Biology (Dispatch)

"Transposable elements (TEs) heavily influence genome size variation between organisms. A new study on larvacean tunicates now shows that even non-autonomous TEs — small TEs that parasitize the enzymatic machinery of large, autonomous TEs — can have a large impact on genome size.”

Highlights

•Genome size varies up to 12× in larvaceans, chordates with a distinctive anatomy

•Small and large species have the smallest and largest genomes, respectively

•Transposable elements have driven multiple independent genome expansions

•Genomes mainly increased through accumulations of non-autonomous elements (SINEs)

Summary—In eukaryotes, genome size correlates little with the number of coding genes or the level of organismal complexity (C-value paradox). The underlying causes of variations in genome size, whether adaptive or neutral, remain unclear, although several biological traits often covary with it . Rapid increases in genome size occur mainly through whole-genome duplications or bursts in the activity of transposable elements (TEs). The very small and compact genome of Oikopleura dioica, a tunicate of the larvacean class, lacks elements of most ancient families of animal retrotransposons . Here, we sequenced the genomes of six other larvaceans, all of which are larger than that of Oikopleura (up to 12 times) and which increase in size with greater body length. Although no evidence was found for whole-genome duplications within the group of species, the global amount of TEs strongly correlated with genome size. Compared to other metazoans, however, the TE diversity was reduced in all species, as observed previously in O. dioica, suggesting a common ancestor with a compacted genome. Strikingly, non-autonomous elements, particularly short interspersed nuclear elements (SINEs), massively contributed to genome size variation through species-specific independent amplifications, ranging from 3% in the smallest genome up to 49% in the largest. Variations in SINE abundance explain as much as 83% of interspecific genome size variation. These data support an indirect influence of autonomous TEs on genome size via their ability to mobilize non-autonomous element

READ HERE… for a summary and here for the original article.

AI for variant classification and clinical reporting

Fabric Genomics Announces AI-based ACMG Classification Solution for Genetic Testing with Hereditary Panels

SEATTLE--(BUSINESS WIRE)--Apr 1, 2019--Fabric Genomics will launch a new solution this week for variant interpretation and clinical reporting, allowing clinical laboratories to dramatically accelerate turnaround times. This new software solution, called Fabric Hereditary Panels with ACE (AI Classification Engine), will debut at the American College of Medical Genetics and Genomics (ACMG) annual meeting in Seattle, Washington. It incorporates an extensively validated, automated ACMG classification engine, enabling laboratories to speed up accurate variant classification and clinical reporting.

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