Browsing by Author "Mahajan, Ragini"

Now showing 1 - 2 of 2
  • Thumbnail Image
    Item
    A rapid, low-cost, and highly sensitive SARS-CoV-2 diagnostic based on whole-genome sequencing
    (Public Library of Science, 2023) Adastra, Per A.; Durand, Neva C.; Mitra, Namita; Pulido, Saul Godinez; Mahajan, Ragini; Blackburn, Alyssa; Colaric, Zane L.; Theisen, Joshua W. M.; Weisz, David; Dudchenko, Olga; Gnirke, Andreas; Rao, Suhas S. P.; Kaur, Parwinder; Aiden, Erez Lieberman; Aiden, Aviva Presser; Center for Theoretical Biological Physics
    Early detection of SARS-CoV-2 infection is key to managing the current global pandemic, as evidence shows the virus is most contagious on or before symptom onset. Here, we introduce a low-cost, high-throughput method for diagnosing and studying SARS-CoV-2 infection. Dubbed Pathogen-Oriented Low-Cost Assembly & Re-Sequencing (POLAR), this method amplifies the entirety of the SARS-CoV-2 genome. This contrasts with typical RT-PCR-based diagnostic tests, which amplify only a few loci. To achieve this goal, we combine a SARS-CoV-2 enrichment method developed by the ARTIC Network (https://artic.network/) with short-read DNA sequencing and de novo genome assembly. Using this method, we can reliably (>95% accuracy) detect SARS-CoV-2 at a concentration of 84 genome equivalents per milliliter (GE/mL). The vast majority of diagnostic methods meeting our analytical criteria that are currently authorized for use by the United States Food and Drug Administration with the Coronavirus Disease 2019 (COVID-19) Emergency Use Authorization require higher concentrations of the virus to achieve this degree of sensitivity and specificity. In addition, we can reliably assemble the SARS-CoV-2 genome in the sample, often with no gaps and perfect accuracy given sufficient viral load. The genotypic data in these genome assemblies enable the more effective analysis of disease spread than is possible with an ordinary binary diagnostic. These data can also help identify vaccine and drug targets. Finally, we show that the diagnoses obtained using POLAR of positive and negative clinical nasal mid-turbinate swab samples 100% match those obtained in a clinical diagnostic lab using the Center for Disease Control’s 2019-Novel Coronavirus test. Using POLAR, a single person can manually process 192 samples over an 8-hour experiment at the cost of ~$36 per patient (as of December 7th, 2022), enabling a 24-hour turnaround with sequencing and data analysis time. We anticipate that further testing and refinement will allow greater sensitivity using this approach.
  • Thumbnail Image
    Item
    Three-dimensional genome architecture persists in a 52,000-year-old woolly mammoth skin sample
    (Elsevier, 2024) Sandoval-Velasco, Marcela; Dudchenko, Olga; Rodríguez, Juan Antonio; Pérez Estrada, Cynthia; Dehasque, Marianne; Fontsere, Claudia; Mak, Sarah S. T.; Khan, Ruqayya; Contessoto, Vinícius G.; Oliveira Junior, Antonio B.; Kalluchi, Achyuth; Zubillaga Herrera, Bernardo J.; Jeong, Jiyun; Roy, Renata P.; Christopher, Ishawnia; Weisz, David; Omer, Arina D.; Batra, Sanjit S.; Shamim, Muhammad S.; Durand, Neva C.; O’Connell, Brendan; Roca, Alfred L.; Plikus, Maksim V.; Kusliy, Mariya A.; Romanenko, Svetlana A.; Lemskaya, Natalya A.; Serdyukova, Natalya A.; Modina, Svetlana A.; Perelman, Polina L.; Kizilova, Elena A.; Baiborodin, Sergei I.; Rubtsov, Nikolai B.; Machol, Gur; Rath, Krisha; Mahajan, Ragini; Kaur, Parwinder; Gnirke, Andreas; Garcia-Treviño, Isabel; Coke, Rob; Flanagan, Joseph P.; Pletch, Kelcie; Ruiz-Herrera, Aurora; Plotnikov, Valerii; Pavlov, Innokentiy S.; Pavlova, Naryya I.; Protopopov, Albert V.; Di Pierro, Michele; Graphodatsky, Alexander S.; Lander, Eric S.; Rowley, M. Jordan; Wolynes, Peter G.; Onuchic, José N.; Dalén, Love; Marti-Renom, Marc A.; Gilbert, M. Thomas P.; Aiden, Erez Lieberman; Center for Theoretical Biological Physics
    Analyses of ancient DNA typically involve sequencing the surviving short oligonucleotides and aligning to genome assemblies from related, modern species. Here, we report that skin from a female woolly mammoth (†Mammuthus primigenius) that died 52,000 years ago retained its ancient genome architecture. We use PaleoHi-C to map chromatin contacts and assemble its genome, yielding 28 chromosome-length scaffolds. Chromosome territories, compartments, loops, Barr bodies, and inactive X chromosome (Xi) superdomains persist. The active and inactive genome compartments in mammoth skin more closely resemble Asian elephant skin than other elephant tissues. Our analyses uncover new biology. Differences in compartmentalization reveal genes whose transcription was potentially altered in mammoths vs. elephants. Mammoth Xi has a tetradic architecture, not bipartite like human and mouse. We hypothesize that, shortly after this mammoth’s death, the sample spontaneously freeze-dried in the Siberian cold, leading to a glass transition that preserved subfossils of ancient chromosomes at nanometer scale.