It’s well known that finding the genetic cause of rare diseases can be complex — that’s why so many remain unsolved. But researchers are beginning to get a grasp on just how complex these conditions can be, thanks to the heightened power of PacBio. PacBio principal scientist Aaron Wenger kicked off a recent webinar with a quote from University of Washington scientist Evan Eichler, who said “there are three key aspects to genetic disease associations: comprehensive variant discovery, accurate allele-frequency determination, and an understanding of the pattern of normal variation and its effect on expression.” Wenger explained how HiFi reads…
The COVID-19 pandemic has brought a sudden urgency to virus research and led many of us to dig more deeply into all the tools available for characterizing viral genomes, from RT-PCR to DNA sequencing. For all their outsized impact on human health, viruses have remarkably small and simple genomes, some just a few thousand bases in length, and most lacking any repetitive structures. With such tidy genomes, you may wonder, why would scientists want to sequence them with a long-read technology like PacBio HiFi reads? Quasispecies develop as variants are introduced to the viral genome through mutations. While it is…
Herculean efforts are being made by scientists around the world to respond quickly to the COVID-19 crisis in a race to understand the virus causing the pandemic and develop diagnostics, vaccines, and therapeutics. But many research questions remain. How can long-read SMRT Sequencing technology help fill the gaps? PacBio microbiology expert Meredith Ashby highlighted several opportunities to support coronavirus research in a recent webinar as part of a day-long virtual conference hosted by LabRoots. Sequencing the viral genome Understanding the basic biology of the virus is essential, and the more detailed our investigation, the better. Highly accurate, long-read sequencing…
We’re pleased to release a short video describing PacBio Sequencing and our latest platform, the Sequel II System. If you’ve ever wondered how Single Molecule, Real-Time (SMRT) Sequencing works, what the Sequel II System is, and what applications are available, this video is a great place to start. We are excited to share the capabilities of our Sequel II System as it makes SMRT Sequencing affordable for scientists in any lab and provides comprehensive views of genomes, transcriptomes, or epigenomes. The Sequel II System also produces highly accurate long reads, known as HiFi reads, to deliver the highest quality sequencing…
Welcome to the Sequencing 101 blog series – where we will provide introductions to sequencing technology, genomics, and much more! If you’re not immersed in the field of DNA sequencing, it can be challenging to keep up with the rapid evolution among all the platforms and technologies on the market. Let’s start with a quick overview of how these different technologies came about — and how each is used today. The evolution of sequencing technology. First Generation Sequencing – Starting the Era of Genomics The process of Sanger sequencing. DNA sequencing as we know it originated in the late…
Matt Hufford, associate professor at Iowa State University, helped produce a 26-line maize pangenome assembly collection Maize researchers have been rejoicing over a New Year’s gift delivered by a group of 33 scientists: A 26-line “pangenome” reference collection. The multi-institutional consortium of researchers used the Sequel System and BioNano Genomics optical mapping to create the assemblies and high-confidence annotations. They released the results on January 9, and in several presentations at the Plant and Animal Genome XXVIII Conference, less than two years after the ambitious project was funded by a $2.8 million National Science Foundation grant. The collection includes comprehensive,…
There’s the genome, the transcriptome, the microbiome… and now the NLRome? Breeders and pathologists have long been interested in uncovering the secrets of plant immunity, and much of their attention has been focused on receptors that can activate immune signalling: cell-surface proteins that recognize microbe-associated molecular patterns (MAMPs), and intracellular proteins that detect pathogen effectors, including nucleotide-binding leucine-rich repeat receptors (NLRs). Hundreds of NLR genes can be found in the genomes of flowering plants. They are believed to form inflammasome-like structures, or resistosomes, that control cell death following pathogen recognition, and are being investigated as candidates for engineering new pathogen…
The PIK3CA oncogene has been the target of intense research scrutiny for decades. Remarkably, though, a new paper in Science today reports completely novel findings about compound mutations that are associated with patients who respond extremely well to targeted therapies. While more studies are needed, this work has important implications for delivering treatment to patients with breast cancer and other common cancers. Neil Vasan “Double PIK3CA mutations in cis increase oncogenicity and sensitivity to PI3Kα inhibitors” comes from lead author Neil Vasan, senior authors Maurizio Scaltriti and José Baselga, and collaborators at Memorial Sloan Kettering Cancer Center, the Icahn School…
Harm van Bakel When MRSA hits your hospital, what do you do? If you’re located in Europe or other places where infection rates are still relatively low, you can take a seek-and-destroy approach, isolating an affected patient and working out in concentric circles to identify contacts and potential transmissions. If you’re in New York City, however, the strategy is not so simple. Hospital-associated infections with methicillin-resistant Staphylococcus aureus are endemic in the Big Apple, and this has required a fresh approach to treat and prevent the costly bacterial menace. At Mount Sinai Hospital, the strategy now involves SMRT Sequencing. Established…
Cover artwork by Daisy S. Lim It was the first multicellular eukaryotic genome sequenced to apparent completion, but it turns out the Caenorhabditis elegans reference that’s been used as a resource for the past 20 years does not exactly correspond with any N2 strain that exists today. Assembled using sequence data from N2 and CB1392 populations of uncertain lineage grown in at least two different laboratories during the 1980s and 1990s, accuracy of the C. elegans reference genome is limited both by genetic variants and by the limitations of the technology of the time (clone-based Sanger technology). It is believed…
It was the coolest critter Erin Bernberg (@ErinBernberg) had ever worked with – quite literally. The senior scientist at the University of Delaware Sequencing and Genotyping Center, a PacBio certified service provider, received a shipment of tiny, live ice worms from Washington State University and immediately faced several challenges. How would she get them out of their ice cubes? How would she isolate DNA from the delicate, dark pigmented creatures? And would she be able to extract enough DNA to sequence? Thanks to the new PacBio low DNA input protocol, the answer to the last question was yes. In fact,…
100 high-quality assemblies released by the Vertebrate Genome Project include the genome of the critically endangered vaquita porpoise With her distinctive dark eyeshadow, grey lipstick-like markings and delicate disposition, she was a natural film star. And her life certainly provided enough drama for any Hollywood blockbuster, complete with high-speed boat chases in pursuit of black market “cocaine of the sea” cartels. Unfortunately, her ending was not a happy one. But efforts by an international consortium of conservation geneticists are making sure her legacy isn’t lost. The DNA of one of the last remaining vaquita porpoises in the world has been…
An ambitious project to sequence 5,000 microbial genomes was jointly initiated by a consortium of 10 institutions across China, including Nankai University, China CDC, Academy of Military Medical Science, Third Institute of Oceanography-Ministry of Natural Resources, South China Sea Institute of Oceanology-CAS, China National Center for Food Safety Risk Assessment, Shandong University, Tianjin University of Science & Technology, East China University of Science and Technology, and Tianjin Biochip Corporation (TBC). TBC, a PacBio service provider in China, has led the sequencing phase of the project, which is expected to be completed by the end of 2019. We recently sat down with…
Patients with myotonic dystrophy type 1 (DM1) want to know their size — the size of the expansion of repeats of the unstable CTG sequences that cause the progressive deterioration of neuromuscular functions that they might face. Size matters to them, because it has been found to correlate with the severity and onset of symptoms, which can range from severe cardiac and respiratory abnormalities and intellectual impairment in children, to muscle weakness, hypersomnolence or cataracts in adults. The earlier the onset, the more severe the symptoms tend to be. The autosomal disorder, which is the most common form of inherited…
To enable better understanding of biology, sequencing data must be accurate and complete. This is especially true when seeking out variants and determining their implications. Luckily, technical and software improvements for SMRT Sequencing are making it easier to efficiently generate genome assemblies with unparalleled accuracy. As presented in a webinar by PacBio Staff Scientist Sarah Kingan (@drsarahdoom) and GoogleAI Genomics Project Lead Andrew Carroll (@acarroll_ATG), HiFi reads enabled by circular consensus sequencing (CCS) on the new Sequel II System challenge the notion that sequencing technologies require a tradeoff between length and accuracy. Highly accurate long reads (HiFi reads) offer the…