Search

Your search keyword '"Starita, Lea"' showing total 435 results
Start Over Author "Starita, Lea"
435 results on '"Starita, Lea"'

1. Guidelines for releasing a variant effect predictor

Author

Livesey, Benjamin J., Badonyi, Mihaly, Dias, Mafalda, Frazer, Jonathan, Kumar, Sushant, Lindorff-Larsen, Kresten, McCandlish, David M., Orenbuch, Rose, Shearer, Courtney A., Muffley, Lara, Foreman, Julia, Glazer, Andrew M., Lehner, Ben, Marks, Debora S., Roth, Frederick P., Rubin, Alan F., Starita, Lea M., and Marsh, Joseph A.

Subjects
Quantitative Biology - Other Quantitative Biology
Abstract

Computational methods for assessing the likely impacts of mutations, known as variant effect predictors (VEPs), are widely used in the assessment and interpretation of human genetic variation, as well as in other applications like protein engineering. Many different VEPs have been released to date, and there is tremendous variability in their underlying algorithms and outputs, and in the ways in which the methodologies and predictions are shared. This leads to considerable challenges for end users in knowing which VEPs to use and how to use them. Here, to address these issues, we provide guidelines and recommendations for the release of novel VEPs. Emphasising open-source availability, transparent methodologies, clear variant effect score interpretations, standardised scales, accessible predictions, and rigorous training data disclosure, we aim to improve the usability and interpretability of VEPs, and promote their integration into analysis and evaluation pipelines. We also provide a large, categorised list of currently available VEPs, aiming to facilitate the discovery and encourage the usage of novel methods within the scientific community., Comment: 14 pages, 1 figure

Published
2024

3. An Atlas of Variant Effects to understand the genome at nucleotide resolution.

Author

Fowler, Douglas, Adams, David, Gloyn, Anna, Hahn, William, Marks, Debora, Muffley, Lara, Neal, James, Roth, Frederick, Rubin, Alan, Starita, Lea, and Hurles, Matthew

Subjects
Functional genomics, Genome interpretation, Global alliance, Multiplexed assay of variant effect, Saturation mutagenesis, Variant effect, Humans, Genetic Variation, Genomics, Genome, Human, High-Throughput Nucleotide Sequencing, Precision Medicine
Abstract

Sequencing has revealed hundreds of millions of human genetic variants, and continued efforts will only add to this variant avalanche. Insufficient information exists to interpret the effects of most variants, limiting opportunities for precision medicine and comprehension of genome function. A solution lies in experimental assessment of the functional effect of variants, which can reveal their biological and clinical impact. However, variant effect assays have generally been undertaken reactively for individual variants only after and, in most cases long after, their first observation. Now, multiplexed assays of variant effect can characterise massive numbers of variants simultaneously, yielding variant effect maps that reveal the function of every possible single nucleotide change in a gene or regulatory element. Generating maps for every protein encoding gene and regulatory element in the human genome would create an Atlas of variant effect maps and transform our understanding of genetics and usher in a new era of nucleotide-resolution functional knowledge of the genome. An Atlas would reveal the fundamental biology of the human genome, inform human evolution, empower the development and use of therapeutics and maximize the utility of genomics for diagnosing and treating disease. The Atlas of Variant Effects Alliance is an international collaborative group comprising hundreds of researchers, technologists and clinicians dedicated to realising an Atlas of Variant Effects to help deliver on the promise of genomics.

Published
2023

5. Single-cell analysis of chromatin and expression reveals age- and sex-associated alterations in the human heart

Author

Read, David F., Booth, Gregory T., Daza, Riza M., Jackson, Dana L., Gladden, Rula Green, Srivatsan, Sanjay R., Ewing, Brent, Franks, Jennifer M., Spurrell, Cailyn H., Gomes, Anne Roshella, O’Day, Diana, Gogate, Aishwarya A., Martin, Beth K., Larson, Haleigh, Pfleger, Christian, Starita, Lea, Lin, Yiing, Shendure, Jay, Lin, Shin, and Trapnell, Cole

Published
2024
Full Text
View/download PDF

6. Impacts of human mobility on the citywide transmission dynamics of 18 respiratory viruses in pre- and post-COVID-19 pandemic years

Author

Perofsky, Amanda C., Hansen, Chelsea L., Burstein, Roy, Boyle, Shanda, Prentice, Robin, Marshall, Cooper, Reinhart, David, Capodanno, Ben, Truong, Melissa, Schwabe-Fry, Kristen, Kuchta, Kayla, Pfau, Brian, Acker, Zack, Lee, Jover, Sibley, Thomas R., McDermot, Evan, Rodriguez-Salas, Leslie, Stone, Jeremy, Gamboa, Luis, Han, Peter D., Adler, Amanda, Waghmare, Alpana, Jackson, Michael L., Famulare, Michael, Shendure, Jay, Bedford, Trevor, Chu, Helen Y., Englund, Janet A., Starita, Lea M., and Viboud, Cécile

Published
2024
Full Text
View/download PDF

8. Beyond the exome: what's next in diagnostic testing for Mendelian conditions

Author

Wojcik, Monica H., Reuter, Chloe M., Marwaha, Shruti, Mahmoud, Medhat, Duyzend, Michael H., Barseghyan, Hayk, Yuan, Bo, Boone, Philip M., Groopman, Emily E., Délot, Emmanuèle C., Jain, Deepti, Sanchis-Juan, Alba, Diseases, Genomics Research to Elucidate the Genetics of Rare, Consortium, Starita, Lea M., Talkowski, Michael, Montgomery, Stephen B., Bamshad, Michael J., Chong, Jessica X., Wheeler, Matthew T., Berger, Seth I., O'Donnell-Luria, Anne, Sedlazeck, Fritz J., and Miller, Danny E.

Subjects
Quantitative Biology - Genomics
Abstract

Despite advances in clinical genetic testing, including the introduction of exome sequencing (ES), more than 50% of individuals with a suspected Mendelian condition lack a precise molecular diagnosis. Clinical evaluation is increasingly undertaken by specialists outside of clinical genetics, often occurring in a tiered fashion and typically ending after ES. The current diagnostic rate reflects multiple factors, including technical limitations, incomplete understanding of variant pathogenicity, missing genotype-phenotype associations, complex gene-environment interactions, and reporting differences between clinical labs. Maintaining a clear understanding of the rapidly evolving landscape of diagnostic tests beyond ES, and their limitations, presents a challenge for non-genetics professionals. Newer tests, such as short-read genome or RNA sequencing, can be challenging to order and emerging technologies, such as optical genome mapping and long-read DNA or RNA sequencing, are not available clinically. Furthermore, there is no clear guidance on the next best steps after inconclusive evaluation. Here, we review why a clinical genetic evaluation may be negative, discuss questions to be asked in this setting, and provide a framework for further investigation, including the advantages and disadvantages of new approaches that are nascent in the clinical sphere. We present a guide for the next best steps after inconclusive molecular testing based upon phenotype and prior evaluation, including when to consider referral to a consortium such as GREGoR, which is focused on elucidating the underlying cause of rare unsolved genetic disorders.

Published
2023
Full Text
View/download PDF

11. Considerations for reporting variants in novel candidate genes identified during clinical genomic testing

Author

Abouhala, Siwaar, Albert, Jessica, Almalvez, Miguel, Alvarez, Raquel, Amin, Mutaz, Anderson, Peter, Aradhya, Swaroop, Ashley, Euan, Assimes, Themistocles, Auriga, Light, Austin-Tse, Christina, Bamshad, Mike, Barseghyan, Hayk, Baxter, Samantha, Behera, Sairam, Beheshti, Shaghayegh, Bejerano, Gill, Berger, Seth, Bernstein, Jon, Best, Sabrina, Blankenmeister, Benjamin, Blue, Elizabeth, Boerwinkle, Eric, Bonkowski, Emily, Bonner, Devon, Boone, Philip, Bornhorst, Miriam, Brand, Harrison, Buckingham, Kati, Calame, Daniel, Carter, Jennefer, Casadei, Silvia, Chadwick, Lisa, Chavez, Clarisa, Chen, Ziwei, Chinn, Ivan, Chong, Jessica, Coban-Akdemir, Zeynep, Cohen, Andrea J., Conner, Sarah, Conomos, Matthew, Coveler, Karen, Cui, Ya Allen, Currin, Sara, Daber, Robert, Dardas, Zain, Davis, Colleen, Dawood, Moez, de Dios, Ivan, de Esch, Celine, Delaney, Meghan, Delot, Emmanuele, DiTroia, Stephanie, Doddapaneni, Harsha, Du, Haowei, Duan, Ruizhi, Dugan-Perez, Shannon, Duong, Nhat, Duyzend, Michael, Eichler, Evan, Emami, Sara, Fraser, Jamie, Fusaro, Vincent, Galey, Miranda, Ganesh, Vijay, Garcia, Brandon, Garimella, Kiran, Gibbs, Richard, Gifford, Casey, Ginsburg, Amy, Goddard, Page, Gogarten, Stephanie, Gogate, Nikhita, Gordon, William, Gorzynski, John E., Greenleaf, William, Grochowski, Christopher, Groopman, Emily, Sousa, Rodrigo Guarischi, Gudmundsson, Sanna, Gulati, Ashima, Hall, Stacey, Harvey, William, Hawley, Megan, Heavner, Ben, Horike-Pyne, Martha, Hu, Jianhong, Huang, Yongqing, Hwang, James, Jarvik, Gail, Jensen, Tanner, Jhangiani, Shalini, Jimenez-Morales, David, Jin, Christopher, Saad, Ahmed K., Kahn-Kirby, Amanda, Kain, Jessica, Kaur, Parneet, Keehan, Laura, Knoblach, Susan, Ko, Arthur, Kundaje, Anshul, Kundu, Soumya, Lancaster, Samuel M., Larsson, Katie, Lee, Arthur, Lemire, Gabrielle, Lewis, Richard, Li, Wei, Li, Yidan, Liu, Pengfei, LoTempio, Jonathan, Lupski, James (Jim), Ma, Jialan, MacArthur, Daniel, Mahmoud, Medhat, Malani, Nirav, Mangilog, Brian, Marafi, Dana, Marmolejos, Sofia, Marten, Daniel, Martinez, Eva, Marvin, Colby, Marwaha, Shruti, Mastrorosa, Francesco Kumara, Matalon, Dena, May, Susanne, McGee, Sean, Meador, Lauren, Mefford, Heather, Mendez, Hector Rodrigo, Miller, Alexander, Miller, Danny E., Mitani, Tadahiro, Montgomery, Stephen, Moyses, Mariana, Munderloh, Chloe, Muzny, Donna, Nelson, Sarah, Nguyen, Thuy-mi P., Nguyen, Jonathan, Nussbaum, Robert, Nykamp, Keith, O'Callaghan, William, O'Heir, Emily, O'Leary, Melanie, Olsen, Jeren, Osei-Owusu, Ikeoluwa, O'Donnell-Luria, Anne, Padhi, Evin, Pais, Lynn, Pan, Miao, Panchal, Piyush, Patterson, Karynne, Payne, Sheryl, Pehlivan, Davut, Petrowski, Paul, Pham, Alicia, Pitsava, Georgia, Podesta, Astaria`Sara, Ponce, Sarah, Porter, Elizabeth, Posey, Jennifer, Prosser, Jaime, Quertermous, Thomas, Rai, Archana, Ramani, Arun, Rehm, Heidi, Reuter, Chloe, Reuter, Jason, Richardson, Matthew, Rivera-Munoz, Andres, Rubio, Oriane, Sabo, Aniko, Salani, Monica, Samocha, Kaitlin, Sanchis-Juan, Alba, Savage, Sarah, Scott, Evette, Scott, Stuart, Sedlazeck, Fritz, Shah, Gulalai, Shojaie, Ali, Singh, Mugdha, Smith, Kevin, Smith, Josh, Snow, Hana, Snyder, Michael, Socarras, Kayla, Starita, Lea, Stark, Brigitte, Stenton, Sarah, Stergachis, Andrew, Stilp, Adrienne, Sutton, V. Reid, Tai, Jui-Cheng, Talkowski, Michael (Mike), Tise, Christina, Tong, Catherine (Cat), Tsao, Philip, Ungar, Rachel, VanNoy, Grace, Vilain, Eric, Voutos, Isabella, Walker, Kim, Wei, Chia-Lin, Weisburd, Ben, Weiss, Jeff, Wellington, Chris, Weng, Ziming, Westheimer, Emily, Wheeler, Marsha, Wheeler, Matthew, Wiel, Laurens, Wilson, Michael, Wojcik, Monica, Wong, Quenna, Xiao, Changrui, Yadav, Rachita, Yi, Qian, Yuan, Bo, Zhao, Jianhua, Zhen, Jimmy, Zhou, Harry, Chong, Jessica X., Berger, Seth I., Smith, Erica, Calame, Daniel G., Hawley, Megan H., Rivera-Munoz, E. Andres, Bamshad, Michael J., and Rehm, Heidi L.

Published
2024
Full Text
View/download PDF

12. Beyond the exome: What’s next in diagnostic testing for Mendelian conditions

Author

Abouhala, Siwaar, Albert, Jessica, Almalvez, Miguel, Alvarez, Raquel, Amin, Mutaz, Anderson, Peter, Aradhya, Swaroop, Ashley, Euan, Assimes, Themistocles, Auriga, Light, Austin-Tse, Christina, Bamshad, Mike, Barseghyan, Hayk, Baxter, Samantha, Behera, Sairam, Beheshti, Shaghayegh, Bejerano, Gill, Berger, Seth, Bernstein, Jon, Best, Sabrina, Blankenmeister, Benjamin, Blue, Elizabeth, Boerwinkle, Eric, Bonkowski, Emily, Bonner, Devon, Boone, Philip, Bornhorst, Miriam, Bozkurt-Yozgatli, Tugce, Brand, Harrison, Buckingham, Kati, Calame, Daniel, Casadei, Silvia, Chadwick, Lisa, Chavez, Clarisa, Chen, Ziwei, Chinn, Ivan, Chong, Jessica, Coban-Akdemir, Zeynep, Cohen, Andrea J., Conner, Sarah, Conomos, Matthew, Coveler, Karen, Cui, Ya Allen, Currin, Sara, Daber, Robert, Dardas, Zain, Davis, Colleen, Dawood, Moez, de Dios, Ivan, de Esch, Celine, Delaney, Meghan, Délot, Emmanuèle, DiTroia, Stephanie, Doddapaneni, Harsha, Du, Haowei, Duan, Ruizhi, Dugan-Perez, Shannon, Duong, Nhat, Duyzend, Michael, Eichler, Evan, Emami, Sara, Fatih, Jawid, Fraser, Jamie, Fusaro, Vincent, Galey, Miranda, Ganesh, Vijay, Garimella, Kiran, Gibbs, Richard, Gifford, Casey, Ginsburg, Amy, Goddard, Pagé, Gogarten, Stephanie, Gogate, Nikhita, Gordon, William, Gorzynski, John E., Greenleaf, William, Grochowski, Christopher, Groopman, Emily, Guarischi Sousa, Rodrigo, Gudmundsson, Sanna, Gulati, Ashima, Guo, Daniel, Hale, Walker, Hall, Stacey, Harvey, William, Hawley, Megan, Heavner, Ben, Herman, Isabella, Horike-Pyne, Martha, Hu, Jianhong, Huang, Yongqing, Hwang, James, Jarvik, Gail, Jensen, Tanner, Jhangiani, Shalini, Jimenez-Morales, David, Jin, Christopher, Saad, Ahmed K., Kahn-Kirby, Amanda, Kain, Jessica, Kaur, Parneet, Keehan, Laura, Knoblach, Susan, Ko, Arthur, Kohler, Jennefer, Kundaje, Anshul, Kundu, Soumya, Lancaster, Samuel M., Larsson, Katie, Lemire, Gabrielle, Lewis, Richard, Li, Wei, Li, Yidan, Liu, Pengfei, LoTempio, Jonathan, Lupski, James, Ma, Jialan, MacArthur, Daniel, Mahmoud, Medhat, Malani, Nirav, Mangilog, Brian, Marafi, Dana, Marmolejos, Sofia, Marten, Daniel, Martinez, Eva, Marvin, Colby, Marwaha, Shruti, Kumara Mastrorosa, Francesco, Matalon, Dena, May, Susanne, McGee, Sean, Meador, Lauren, Mefford, Heather, Rodrigo Mendez, Hector, Miller, Alexander, Miller, Danny E., Mitani, Tadahiro, Montgomery, Stephen, Moussa, Hala Mohamed, Moyses, Mariana, Munderloh, Chloe, Muzny, Donna, Nelson, Sarah, Neu, Matthew B., Nguyen, Jonathan, Nguyen, Thuy-mi P., Nussbaum, Robert, Nykamp, Keith, O'Callaghan, William, O'Heir, Emily, O'Leary, Melanie, Olsen, Jeren, Osei-Owusu, Ikeoluwa, O'Donnell-Luria, Anne, Padhi, Evin, Pais, Lynn, Pan, Miao, Panchal, Piyush, Patterson, Karynne, Payne, Sheryl, Pehlivan, Davut, Petrowski, Paul, Pham, Alicia, Pitsava, Georgia, Podesta, Astaria, Ponce, Sarah, Posey, Jennifer, Prosser, Jaime, Quertermous, Thomas, Rai, Archana, Ramani, Arun, Rehm, Heidi, Reuter, Chloe, Reuter, Jason, Richardson, Matthew, Rivera-Munoz, Andres, Rubio, Oriane, Sabo, Aniko, Salani, Monica, Samocha, Kaitlin, Sanchis-Juan, Alba, Savage, Sarah, Scott, Stuart, Scott, Evette, Sedlazeck, Fritz, Shah, Gulalai, Shojaie, Ali, Singh, Mugdha, Smith, Josh, Smith, Kevin, Snow, Hana, Snyder, Michael, Socarras, Kayla, Starita, Lea, Stark, Brigitte, Stenton, Sarah, Stergachis, Andrew, Stilp, Adrienne, Sundaram, Laksshman, Sutton, V. Reid, Tai, Jui-Cheng, Talkowski, Michael, Tise, Christina, Tong, Catherine, Tsao, Philip, Ungar, Rachel, VanNoy, Grace, Vilain, Eric, Voutos, Isabella, Walker, Kim, Weisburd, Ben, Weiss, Jeff, Wellington, Chris, Weng, Ziming, Westheimer, Emily, Wheeler, Marsha, Wheeler, Matthew, Wiel, Laurens, Wilson, Michael, Wojcik, Monica, Wong, Quenna, Wong, Issac, Xiao, Changrui, Yadav, Rachita, Yi, Qian, Yuan, Bo, Zhao, Jianhua, Zhen, Jimmy, Zhou, Harry, Wojcik, Monica H., Reuter, Chloe M., Duyzend, Michael H., Boone, Philip M., Groopman, Emily E., Délot, Emmanuèle C., Jain, Deepti, Starita, Lea M., Montgomery, Stephen B., Bamshad, Michael J., Chong, Jessica X., Wheeler, Matthew T., Berger, Seth I., and Sedlazeck, Fritz J.

Published
2023
Full Text
View/download PDF

13. Antibacterial potency of type VI amidase effector toxins is dependent on substrate topology and cellular context

Author

Radkov, Atanas, Sapiro, Anne L, Flores, Sebastian, Henderson, Corey, Saunders, Hayden, Kim, Rachel, Massa, Steven, Thompson, Samuel, Mateusiak, Chase, Biboy, Jacob, Zhao, Ziyi, Starita, Lea M, Hatleberg, William L, Vollmer, Waldemar, Russell, Alistair B, Simorre, Jean-Pierre, Anthony-Cahill, Spencer, Brzovic, Peter, Hayes, Beth, and Chou, Seemay

Subjects
Biochemistry and Cell Biology, Biological Sciences, Infectious Diseases, Rare Diseases, Aetiology, 2.2 Factors relating to the physical environment, Infection, Amidohydrolases, Anti-Bacterial Agents, Bacterial Proteins, Cell Wall, Peptidoglycan, Pseudomonas aeruginosa, E. coli, biochemistry, chemical biology, cognate immunity, deep mutational scanning, host–microbe interaction, infectious disease, microbiology, peptidoglycan, topology, type VI amidase effector, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Members of the bacterial T6SS amidase effector (Tae) superfamily of toxins are delivered between competing bacteria to degrade cell wall peptidoglycan. Although Taes share a common substrate, they exhibit distinct antimicrobial potency across different competitor species. To investigate the molecular basis governing these differences, we quantitatively defined the functional determinants of Tae1 from Pseudomonas aeruginosa PAO1 using a combination of nuclear magnetic resonance and a high-throughput in vivo genetic approach called deep mutational scanning (DMS). As expected, combined analyses confirmed the role of critical residues near the Tae1 catalytic center. Unexpectedly, DMS revealed substantial contributions to enzymatic activity from a much larger, ring-like functional hot spot extending around the entire circumference of the enzyme. Comparative DMS across distinct growth conditions highlighted how functional contribution of different surfaces is highly context-dependent, varying alongside composition of targeted cell walls. These observations suggest that Tae1 engages with the intact cell wall network through a more distributed three-dimensional interaction interface than previously appreciated, providing an explanation for observed differences in antimicrobial potency across divergent Gram-negative competitors. Further binding studies of several Tae1 variants with their cognate immunity protein demonstrate that requirements to maintain protection from Tae activity may be a significant constraint on the mutational landscape of tae1 toxicity in the wild. In total, our work reveals that Tae diversification has likely been shaped by multiple independent pressures to maintain interactions with binding partners that vary across bacterial species and conditions.

Published
2022

14. Utilizing a university testing program to estimate relative effectiveness of monovalent COVID-19 mRNA booster vaccine versus two-dose primary series against symptomatic SARS-CoV-2 infection

Author

Bennett, Julia C., Luiten, Kyle G., O'Hanlon, Jessica, Han, Peter D., McDonald, Devon, Wright, Tessa, Wolf, Caitlin R., Lo, Natalie K., Acker, Zack, Regelbrugge, Lani, McCaffrey, Kathryn M., Pfau, Brian, Stone, Jeremey, Schwabe-Fry, Kristen, Lockwood, Christina M., Guthrie, Brandon L., Gottlieb, Geoffrey S., Englund, Janet A., Uyeki, Timothy M., Carone, Marco, Starita, Lea M., Weil, Ana A., and Chu, Helen Y.

Published
2024
Full Text
View/download PDF

15. Sentinel Surveillance System Implementation and Evaluation for SARS-CoV-2 Genomic Data, Washington, USA, 2020-2021

Author

Oltean, Hanna N., Allen, Krisandra J., Frisbie, Lauren, Lunn, Stephanie M., Torres, Laura Marcela, Manahan, Lillian, Painter, Ian, Russel, Denny, Singh, Avi, Aric, JohnAric MoonDance, Grant, Kristin, Peter, Cara, Cao, Rebecca, Garcia, Katelynn, Mackellar, Drew, Jones, Lisa, Halstead, Holly, Gray, Hannah, Melly, Geoff, Nickerson, Deborah, Starita, Lea, Frazar, Chris, Greninger, Alexander L., Roychoudhury, Pavitra, Mathias, Patrick C., Kalnoski, Michael H., Ting, Chao-Nan, Lykken, Marisa, and Rice, Tana

Subjects
Washington -- Health aspects, Epidemics -- Statistics -- Genetic aspects, Sentinel health events -- Methods, Data entry -- Methods, Health
Abstract

Virus genome data can provide useful information for public health practice, particularly when combined with epidemiologic data in real time. Goals of genomic surveillance can include monitoring circulating and emerging [...]

Published
2023
Full Text
View/download PDF

16. Single-cell census of human tooth development enables generation of human enamel

Author

Alghadeer, Ammar, Hanson-Drury, Sesha, Patni, Anjali P., Ehnes, Devon D., Zhao, Yan Ting, Li, Zicong, Phal, Ashish, Vincent, Thomas, Lim, Yen C., O’Day, Diana, Spurrell, Cailyn H., Gogate, Aishwarya A., Zhang, Hai, Devi, Arikketh, Wang, Yuliang, Starita, Lea, Doherty, Dan, Glass, Ian A., Shendure, Jay, Freedman, Benjamin S., Baker, David, Regier, Mary C., Mathieu, Julie, and Ruohola-Baker, Hannele

Published
2023
Full Text
View/download PDF

17. High-frequency home self-collection of capillary blood correlates IFI27 expression kinetics with SARS-CoV-2 viral clearance

Author

Lim, Fang Yun, Kim, Soo-Young, Kulkarni, Karisma N., Blazevic, Rachel L., Kimball, Louise E., Lea, Hannah G., Haack, Amanda J., Gower, Maia S., Stevens-Ayers, Terry, Starita, Lea M., Boeckh, Michael, Hyrien, Ollivier, Schiffer, Joshua T., Theberge, Ashleigh B., and Waghmare, Alpana

Subjects
Blood banks -- Health aspects, Health care industry
Abstract

To the Editor: Blood transcriptional profiling is a powerful tool to evaluate immune responses to infection; however, blood collection via traditional phlebotomy remains a barrier to precise characterization of the [...]

Published
2023

18. Human Parainfluenza Virus in Homeless Shelters before and during the COVID-19 Pandemic, Washington, USA

Author

Chow, Eric J., Casto, Amanda M., Sampoleo, Reigran, Mills, Margaret G., Han, Peter D., Xie, Hong, Pfau, Brian, Nguyen, Tien V., Sereewit, Jaydee, Rogers, Julia H., Cox, Sarah N., Rolfes, Melissa A., Ogokeh, Constance, Mosites, Emily, Uyeki, Timothy M., Greninger, Alexander L., Hughes, James P., Shim, M. Mia, Sugg, Nancy, Duchin, Jeffrey S., Starita, Lea M., Englund, Janet A., Roychoudhury, Pavitra, and Chu, Helen Y.

Subjects
Washington -- Health aspects, Parainfluenza viruses -- Distribution, Respiratory tract infections -- Causes of -- Demographic aspects, Pediatric research, Homeless shelters -- Health aspects, Company distribution practices, Health
Abstract

Human parainfluenza virus (HPIV) contributes to acute respiratory tract infection burden in young children (1) and adults (2). Persons experiencing homelessness are among those at risk for respiratory viral complications [...]

Published
2022
Full Text
View/download PDF

20. Multiplexed Functional Assessment of Genetic Variants in CARD11

Author

Meitlis, Iana, Allenspach, Eric J, Bauman, Bradly M, Phan, Isabelle Q, Dabbah, Gina, Schmitt, Erica G, Camp, Nathan D, Torgerson, Troy R, Nickerson, Deborah A, Bamshad, Michael J, Hagin, David, Luthers, Christopher R, Stinson, Jeffrey R, Gray, Jessica, Lundgren, Ingrid, Church, Joseph A, Butte, Manish J, Jordan, Mike B, Aceves, Seema S, Schwartz, Daniella M, Milner, Joshua D, Schuval, Susan, Skoda-Smith, Suzanne, Cooper, Megan A, Starita, Lea M, Rawlings, David J, Snow, Andrew L, and James, Richard G

Subjects
Biological Sciences, Biomedical and Clinical Sciences, Genetics, Genetic Testing, Human Genome, Biotechnology, Good Health and Well Being, Adenine, B-Cell CLL-Lymphoma 10 Protein, B-Lymphocytes, CARD Signaling Adaptor Proteins, Cell Line, Diploidy, Exons, Genes, Dominant, Genetic Variation, Guanylate Cyclase, Humans, Immunologic Deficiency Syndromes, Jurkat Cells, Lymphoma, NF-kappa B p50 Subunit, Piperidines, Polymorphism, Single Nucleotide, Primary Immunodeficiency Diseases, Sensitivity and Specificity, B cells, CARD11, gene editing, immune dysregulation, lymphoma, primary immune deficiency, saturation genome editing, variant interpretation, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Genetic testing has increased the number of variants identified in disease genes, but the diagnostic utility is limited by lack of understanding variant function. CARD11 encodes an adaptor protein that expresses dominant-negative and gain-of-function variants associated with distinct immunodeficiencies. Here, we used a "cloning-free" saturation genome editing approach in a diploid cell line to simultaneously score 2,542 variants for decreased or increased function in the region of CARD11 associated with immunodeficiency. We also described an exon-skipping mechanism for CARD11 dominant-negative activity. The classification of reported clinical variants was sensitive (94.6%) and specific (88.9%), which rendered the data immediately useful for interpretation of seven coding and splicing variants implicated in immunodeficiency found in our clinic. This approach is generalizable for variant interpretation in many other clinically actionable genes, in any relevant cell type.

Published
2020

21. Cryptic transmission of SARS-CoV-2 in Washington state

Author

Bedford, Trevor, Greninger, Alexander L, Roychoudhury, Pavitra, Starita, Lea M, Famulare, Michael, Huang, Meei-Li, Nalla, Arun, Pepper, Gregory, Reinhardt, Adam, Xie, Hong, Shrestha, Lasata, Nguyen, Truong N, Adler, Amanda, Brandstetter, Elisabeth, Cho, Shari, Giroux, Danielle, Han, Peter D, Fay, Kairsten, Frazar, Chris D, Ilcisin, Misja, Lacombe, Kirsten, Lee, Jover, Kiavand, Anahita, Richardson, Matthew, Sibley, Thomas R, Truong, Melissa, Wolf, Caitlin R, Nickerson, Deborah A, Rieder, Mark J, Englund, Janet A, Hadfield, James, Hodcroft, Emma B, Huddleston, John, Moncla, Louise H, Müller, Nicola F, Neher, Richard A, Deng, Xianding, Gu, Wei, Federman, Scot, Chiu, Charles, Duchin, Jeffrey S, Gautom, Romesh, Melly, Geoff, Hiatt, Brian, Dykema, Philip, Lindquist, Scott, Queen, Krista, Tao, Ying, Uehara, Anna, Tong, Suxiang, MacCannell, Duncan, Armstrong, Gregory L, Baird, Geoffrey S, Chu, Helen Y, Shendure, Jay, Jerome, Keith R, Boeckh, Michael, Lutz, Barry R, Thompson, Matthew, Huang, Shichu, Jackson, Michael L, Kimball, Louise E, Logue, Jennifer, Lyon, Victoria, Newman, Kira L, and Suchsland, Monica L Zigman

Subjects
Infectious Diseases, Pneumonia & Influenza, Lung, Prevention, Emerging Infectious Diseases, Biodefense, Vaccine Related, Pneumonia, Infection, Good Health and Well Being, Bayes Theorem, Betacoronavirus, COVID-19, Coronavirus Infections, Genome, Viral, Humans, Likelihood Functions, Pandemics, Phylogeny, Pneumonia, Viral, SARS-CoV-2, Washington, Seattle Flu Study Investigators, General Science & Technology
Abstract

After its emergence in Wuhan, China, in late November or early December 2019, the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus rapidly spread globally. Genome sequencing of SARS-CoV-2 allows the reconstruction of its transmission history, although this is contingent on sampling. We analyzed 453 SARS-CoV-2 genomes collected between 20 February and 15 March 2020 from infected patients in Washington state in the United States. We find that most SARS-CoV-2 infections sampled during this time derive from a single introduction in late January or early February 2020, which subsequently spread locally before active community surveillance was implemented.

Published
2020

22. Multiregion transcriptomic profiling of the primate brain reveals signatures of aging and the social environment

Author

Chiou, Kenneth L., DeCasien, Alex R., Rees, Katherina P., Testard, Camille, Spurrell, Cailyn H., Gogate, Aishwarya A., Pliner, Hannah A., Tremblay, Sébastien, Mercer, Arianne, Whalen, Connor J., Negrón-Del Valle, Josué E., Janiak, Mareike C., Bauman Surratt, Samuel E., González, Olga, Compo, Nicole R., Stock, Michala K., Ruiz-Lambides, Angelina V., Martínez, Melween I., Wilson, Melissa A., Melin, Amanda D., Antón, Susan C., Walker, Christopher S., Sallet, Jérôme, Newbern, Jason M., Starita, Lea M., Shendure, Jay, Higham, James P., Brent, Lauren J. N., Montague, Michael J., Platt, Michael L., and Snyder-Mackler, Noah

Published
2022
Full Text
View/download PDF

24. Genomic surveillance reveals multiple introductions of SARS-CoV-2 into Northern California

Author

Deng, Xianding, Gu, Wei, Federman, Scot, du Plessis, Louis, Pybus, Oliver G, Faria, Nuno, Wang, Candace, Yu, Guixia, Bushnell, Brian, Pan, Chao-Yang, Guevara, Hugo, Sotomayor-Gonzalez, Alicia, Zorn, Kelsey, Gopez, Allan, Servellita, Venice, Hsu, Elaine, Miller, Steve, Bedford, Trevor, Greninger, Alexander L, Roychoudhury, Pavitra, Starita, Lea M, Famulare, Michael, Chu, Helen Y, Shendure, Jay, Jerome, Keith R, Anderson, Catie, Gangavarapu, Karthik, Zeller, Mark, Spencer, Emily, Andersen, Kristian G, MacCannell, Duncan, Paden, Clinton R, Li, Yan, Zhang, Jing, Tong, Suxiang, Armstrong, Gregory, Morrow, Scott, Willis, Matthew, Matyas, Bela T, Mase, Sundari, Kasirye, Olivia, Park, Maggie, Masinde, Godfred, Chan, Curtis, Yu, Alexander T, Chai, Shua J, Villarino, Elsa, Bonin, Brandon, Wadford, Debra A, and Chiu, Charles Y

Subjects
Pneumonia, Lung, Infectious Diseases, Emerging Infectious Diseases, Vaccine Related, Pneumonia & Influenza, Prevention, Biodefense, Infection, Good Health and Well Being, Betacoronavirus, COVID-19, California, Coronavirus Infections, Epidemiological Monitoring, Genome, Viral, Humans, Pandemics, Phylogeny, Pneumonia, Viral, SARS-CoV-2, Sequence Alignment, Ships, Travel, Washington, General Science & Technology
Abstract

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has spread globally, with >365,000 cases in California as of 17 July 2020. We investigated the genomic epidemiology of SARS-CoV-2 in Northern California from late January to mid-March 2020, using samples from 36 patients spanning nine counties and the Grand Princess cruise ship. Phylogenetic analyses revealed the cryptic introduction of at least seven different SARS-CoV-2 lineages into California, including epidemic WA1 strains associated with Washington state, with lack of a predominant lineage and limited transmission among communities. Lineages associated with outbreak clusters in two counties were defined by a single base substitution in the viral genome. These findings support contact tracing, social distancing, and travel restrictions to contain the spread of SARS-CoV-2 in California and other states.

Published
2020

25. SwabExpress: An end-to-end protocol for extraction-free COVID-19 testing

Author

Srivatsan, Sanjay, Heidl, Sarah, Pfau, Brian, Martin, Beth K, Han, Peter D, Zhong, Weizhi, van Raay, Katrina, McDermot, Evan, Opsahl, Jordan, Gamboa, Luis, Smith, Nahum, Truong, Melissa, Cho, Shari, Barrow, Kaitlyn A, Rich, Lucille M, Stone, Jeremy, Wolf, Caitlin R, McCulloch, Denise J, Kim, Ashley E, Brandstetter, Elisabeth, Sohlberg, Sarah L, Ilcisin, Misja, Geyer, Rachel E, Chen, Wei, Gehring, Jase, Investigators, Seattle Flu Study, Kosuri, Sriram, Bedford, Trevor, Rieder, Mark J, Nickerson, Deborah A, Chu, Helen Y, Konnick, Eric Q, Debley, Jason S, Shendure, Jay, Lockwood, Christina M, and Starita, Lea M

Subjects
Biomedical and Clinical Sciences, Clinical Sciences, Lung, HIV/AIDS, Clinical Research, Good Health and Well Being, Seattle Flu Study Investigators
Abstract

The urgent need for massively scaled clinical or surveillance testing for SARS-CoV-2 has necessitated a reconsideration of the methods by which respiratory samples are collected, transported, processed and tested. Conventional testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab, storage of the swab during transport in universal transport medium (UTM), extraction of RNA, and quantitative reverse transcription PCR (RT-qPCR). As testing has scaled across the world, supply chain challenges have emerged across this entire workflow. Here we sought to evaluate how eliminating the UTM storage and RNA extraction steps would impact the results of molecular testing. Using paired mid-turbinate swabs self-collected by 11 individuals with previously established SARS-CoV-2 positivity, we performed a comparison of conventional (swab → UTM → RNA extraction → RT-qPCR) vs. simplified (direct elution from dry swab → RT-qPCR) protocols. Our results suggest that dry swabs eluted directly into a simple buffered solution (TE) can support molecular detection of SARS-CoV-2 via endpoint RT-qPCR without substantially compromising sensitivity. Although further confirmation with a larger sample size and variation of other parameters is necessary, these results are encouraging for the possibility of a simplified workflow that could support massively scaled testing for COVID-19 control.

Published
2020

26. Preliminary support for a "dry swab, extraction free" protocol for SARS-CoV-2 testing via RT-qPCR.

Author

Srivatsan, Sanjay, Han, Peter D, van Raay, Katrina, Wolf, Caitlin R, McCulloch, Denise J, Kim, Ashley E, Brandstetter, Elisabeth, Martin, Beth, Gehring, Jase, Chen, Wei, Seattle Flu Study Investigators, Kosuri, Sriram, Konnick, Eric Q, Lockwood, Christina M, Rieder, Mark J, Nickerson, Deborah A, Chu, Helen Y, Shendure, Jay, and Starita, Lea M

Subjects
Seattle Flu Study Investigators
Abstract

The urgent need for massively scaled clinical or surveillance testing for SARS-CoV-2 has necessitated a reconsideration of the methods by which respiratory samples are collected, transported, processed and tested. Conventional testing for SARS-CoV-2 involves collection of a clinical specimen with a nasopharyngeal swab, storage of the swab during transport in universal transport medium (UTM), extraction of RNA, and quantitative reverse transcription PCR (RT-qPCR). As testing has scaled across the world, supply chain challenges have emerged across this entire workflow. Here we sought to evaluate how eliminating the UTM storage and RNA extraction steps would impact the results of molecular testing. Using paired mid-turbinate swabs self-collected by 11 individuals with previously established SARS-CoV-2 positivity, we performed a comparison of conventional (swab → UTM → RNA extraction → RT-qPCR) vs. simplified (direct elution from dry swab → RT-qPCR) protocols. Our results suggest that dry swabs eluted directly into a simple buffered solution (TE) can support molecular detection of SARS-CoV-2 via endpoint RT-qPCR without substantially compromising sensitivity. Although further confirmation with a larger sample size and variation of other parameters is necessary, these results are encouraging for the possibility of a simplified workflow that could support massively scaled testing for COVID-19 control.

Published
2020

27. A Genomic Survey of SARS-CoV-2 Reveals Multiple Introductions into Northern California without a Predominant Lineage

Author

Deng, Xianding, Gu, Wei, Federman, Scot, du Plessis, Louis, Pybus, Oliver G, Faria, Nuno, Wang, Candace, Yu, Guixia, Pan, Chao-Yang, Guevara, Hugo, Sotomayor-Gonzalez, Alicia, Zorn, Kelsey, Gopez, Allan, Servellita, Venice, Hsu, Elaine, Miller, Steve, Bedford, Trevor, Greninger, Alexander L, Roychoudhury, Pavitra, Starita, Lea M, Famulare, Michael, Chu, Helen Y, Shendure, Jay, Jerome, Keith R, Anderson, Catie, Gangavarapu, Karthik, Zeller, Mark, Spencer, Emily, Andersen, Kristian G, MacCannell, Duncan, Paden, Clinton R, Li, Yan, Zhang, Jing, Tong, Suxiang, Armstrong, Gregory, Morrow, Scott, Willis, Matthew, Matyas, Bela T, Mase, Sundari, Kasirye, Olivia, Park, Maggie, Chan, Curtis, Yu, Alexander T, Chai, Shua J, Villarino, Elsa, Bonin, Brandon, Wadford, Debra A, and Chiu, Charles Y

Subjects
Medical Microbiology, Biomedical and Clinical Sciences, Biological Sciences, Lung, Infectious Diseases, Biotechnology, Prevention, Biodefense, Emerging Infectious Diseases, Vaccine Related, Aetiology, 2.2 Factors relating to the physical environment, Infection, Good Health and Well Being
Abstract

The COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2 has spread globally, resulting in >300,000 reported cases worldwide as of March 21st, 2020. Here we investigate the genetic diversity and genomic epidemiology of SARS-CoV-2 in Northern California using samples from returning travelers, cruise ship passengers, and cases of community transmission with unclear infection sources. Virus genomes were sampled from 29 patients diagnosed with COVID-19 infection from Feb 3rd through Mar 15th. Phylogenetic analyses revealed at least 8 different SARS-CoV-2 lineages, suggesting multiple independent introductions of the virus into the state. Virus genomes from passengers on two consecutive excursions of the Grand Princess cruise ship clustered with those from an established epidemic in Washington State, including the WA1 genome representing the first reported case in the United States on January 19th. We also detected evidence for presumptive transmission of SARS-CoV-2 lineages from one community to another. These findings suggest that cryptic transmission of SARS-CoV-2 in Northern California to date is characterized by multiple transmission chains that originate via distinct introductions from international and interstate travel, rather than widespread community transmission of a single predominant lineage. Rapid testing and contact tracing, social distancing, and travel restrictions are measures that will help to slow SARS-CoV-2 spread in California and other regions of the USA.

Published
2020

28. Evaluation of a novel university-based testing platform to increase access to SARS-CoV-2 testing during the COVID-19 pandemic in a cohort study

Author

Bennett, Julia Catherine, primary, O’Hanlon, Jessica, additional, Acker, Zachary, additional, Han, Peter D, additional, McDonald, Devon, additional, Wright, Tessa, additional, Luiten, Kyle G, additional, Regelbrugge, Lani, additional, McCaffrey, Kathryn M, additional, Pfau, Brian, additional, Wolf, Caitlin R, additional, Gottlieb, Geoffrey S, additional, Hughes, James P, additional, Carone, Marco, additional, Starita, Lea M, additional, Chu, Helen Y, additional, and Weil, Ana A, additional

Published
2024
Full Text
View/download PDF

29. Fine-scale spatial and social patterns of SARS-CoV-2 transmission from identical pathogen sequences

Author

Tran-Kiem, Cécile, primary, Paredes, Miguel I., additional, Perofsky, Amanda C., additional, Frisbie, Lauren A., additional, Xie, Hong, additional, Kong, Kevin, additional, Weixler, Amelia, additional, Greninger, Alexander L., additional, Roychoudhury, Pavitra, additional, Peterson, JohnAric M., additional, Delgado, Andrew, additional, Holstead, Holly, additional, MacKellar, Drew, additional, Dykema, Philip, additional, Gamboa, Luis, additional, Frazar, Chris D., additional, Ryke, Erica, additional, Stone, Jeremy, additional, Reinhart, David, additional, Starita, Lea, additional, Thibodeau, Allison, additional, Yun, Cory, additional, Aragona, Frank, additional, Black, Allison, additional, Viboud, Cécile, additional, and Bedford, Trevor, additional

Published
2024
Full Text
View/download PDF

30. Defining and Reducing Variant Classification Disparities

Author

Dawood, Moez, primary, Fayer, Shawn, additional, Pendyala, Sriram, additional, Post, Mason, additional, Kalra, Divya, additional, Patterson, Karynne, additional, Venner, Eric, additional, Muffley, Lara A., additional, Fowler, Douglas M., additional, Rubin, Alan F., additional, Posey, Jennifer E., additional, Plon, Sharon E., additional, Lupski, James R., additional, Gibbs, Richard A., additional, Starita, Lea M., additional, Robles-Espinoza, Carla Daniela, additional, Coyote-Maestas, Willow, additional, and Gallego Romero, Irene, additional

Published
2024
Full Text
View/download PDF

31. The clinical and genomic epidemiology of seasonal human coronaviruses in congregate homeless shelter settings: A repeated cross-sectional study

Author

Chow, Eric J., Casto, Amanda M., Rogers, Julia H., Roychoudhury, Pavitra, Han, Peter D., Xie, Hong, Mills, Margaret G., Nguyen, Tien V., Pfau, Brian, Cox, Sarah N., Wolf, Caitlin R., Hughes, James P., Uyeki, Timothy M., Rolfes, Melissa A., Mosites, Emily, Shim, M. Mia, Duchin, Jeffrey S., Sugg, Nancy, Starita, Lea A., Englund, Janet A., and Chu, Helen Y.

Published
2022
Full Text
View/download PDF

32. Genomic surveillance of SARS-CoV-2 Omicron variants on a university campus

Author

Weil, Ana A., Luiten, Kyle G., Casto, Amanda M., Bennett, Julia C., O’Hanlon, Jessica, Han, Peter D., Gamboa, Luis S., McDermot, Evan, Truong, Melissa, Gottlieb, Geoffrey S., Acker, Zack, Wolf, Caitlin R., Magedson, Ariana, Chow, Eric J., Lo, Natalie K., Pothan, Lincoln C., McDonald, Devon, Wright, Tessa C., McCaffrey, Kathryn M., Figgins, Marlin D., Englund, Janet A., Boeckh, Michael, Lockwood, Christina M., Nickerson, Deborah A., Shendure, Jay, Bedford, Trevor, Hughes, James P., Starita, Lea M., and Chu, Helen Y.

Published
2022
Full Text
View/download PDF

33. "I probably shouldn't go in today": Inequitable access to paid sick leave and its impacts on health behaviors during the emergence of COVID-19 in the Seattle area.

Author

Iwu, Chidozie D., Cox, Sarah N., Sohlberg, Sarah L., Kim, Ashley E., Logue, Jennifer, Han, Peter D., Sibley, Thomas R., Ilcisin, Misja, Fay, Kairsten A., Lee, Jover, McCulloch, Denise J., Wang, Yongzhe, Boeckh, Michael, Englund, Janet A., Starita, Lea M., Hajat, Anjum, and Chu, Helen Y.

Abstract

This study examines inequities in access to paid sick leave (PSL) by race/ethnicity, income, and sex and the role of PSL access on leave-taking and care-seeking behaviors among Seattle-area workers in the months leading up to and during the emergence of COVID-19 in the region. Survey responses were collected online and in-person from individuals experiencing acute respiratory illness symptoms between November 2019 and March 2020 as part of a community-based respiratory viral surveillance study. Chi-square tests and log-binomial models were used to assess the association between PSL access and various socioeconomic indicators. A total of 66.6% (n = 2,276) respondents reported access to PSL. Proportionally, access to PSL was highest in respondents identifying as Asian (70.5%), followed by White (68.7%), Latine (58.4%), Multiracial (57.1%), Black (47.1%), and Other (43.1%). Access to PSL increased with household income. Eighty three percent of high-income respondents reported access compared to 52.9% of low-income households. Only 23.3% of the lowest-income households reported access to PSL. Fewer females (65.2%) than males (70.7%) reported access to PSL. Access to PSL is inequitably distributed across income, race/ethnicity, and sex. This study reinforces the vast body of knowledge on how socioeconomic inequalities increase individual and community-level vulnerability to the impacts of infectious disease outbreaks. It also supports the role of labor and economic policy in mitigating (or exacerbating) these impacts. Exemplified by the COVID-19 pandemic, universal access to PSL, especially for marginalized populations, benefits all. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

34. Deciphering the impact of genomic variation on function.

Author

Engreitz, Jesse M., Lawson, Heather A., Singh, Harinder, Starita, Lea M., Hon, Gary C., Carter, Hannah, Sahni, Nidhi, Reddy, Timothy E., Lin, Xihong, Li, Yun, Munshi, Nikhil V., Chahrour, Maria H., Boyle, Alan P., Hitz, Benjamin C., Mortazavi, Ali, Craven, Mark, Mohlke, Karen L., Pinello, Luca, Wang, Ting, and Kundaje, Anshul

Abstract

Our genomes influence nearly every aspect of human biology—from molecular and cellular functions to phenotypes in health and disease. Studying the differences in DNA sequence between individuals (genomic variation) could reveal previously unknown mechanisms of human biology, uncover the basis of genetic predispositions to diseases, and guide the development of new diagnostic tools and therapeutic agents. Yet, understanding how genomic variation alters genome function to influence phenotype has proved challenging. To unlock these insights, we need a systematic and comprehensive catalogue of genome function and the molecular and cellular effects of genomic variants. Towards this goal, the Impact of Genomic Variation on Function (IGVF) Consortium will combine approaches in single-cell mapping, genomic perturbations and predictive modelling to investigate the relationships among genomic variation, genome function and phenotypes. IGVF will create maps across hundreds of cell types and states describing how coding variants alter protein activity, how noncoding variants change the regulation of gene expression, and how such effects connect through gene-regulatory and protein-interaction networks. These experimental data, computational predictions and accompanying standards and pipelines will be integrated into an open resource that will catalyse community efforts to explore how our genomes influence biology and disease across populations.The Impact of Genomic Variation on Function Consortium is combining single-cell mapping, genomic perturbations and predictive modelling to investigate relationships between human genomic variation, genome function and phenotypes and will provide an open resource to the community. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

35. Comparative Diagnostic Utility of SARS-CoV-2 Rapid Antigen and Molecular Testing in a Community Setting.

Author

Kim, Ashley E, Bennett, Julia C, Luiten, Kyle, O'Hanlon, Jessica A, Wolf, Caitlin R, Magedson, Ariana, Han, Peter D, Acker, Zack, Regelbrugge, Lani, McCaffrey, Kathryn M, Stone, Jeremey, Reinhart, David, Capodanno, Benjamin J, Morse, Stephen S, Bedford, Trevor, Englund, Janet A, Boeckh, Michael, Starita, Lea M, Uyeki, Timothy M, and Carone, Marco

Subjects
REVERSE transcriptase polymerase chain reaction, RAPID diagnostic tests, SARS-CoV-2 Omicron variant, ANTIGEN analysis, SARS-CoV-2
Abstract

Background SARS-CoV-2 antigen-detection rapid diagnostic tests (Ag-RDTs) have become widely utilized but longitudinal characterization of their community-based performance remains incompletely understood. Methods This prospective longitudinal study at a large public university in Seattle, WA utilized remote enrollment, online surveys, and self-collected nasal swab specimens to evaluate Ag-RDT performance against real-time reverse transcription polymerase chain reaction (rRT-PCR) in the context of SARS-CoV-2 Omicron. Ag-RDT sensitivity and specificity within 1 day of rRT-PCR were evaluated by symptom status throughout the illness episode and Orf1b cycle threshold (Ct). Results From February to December 2022, 5757 participants reported 17 572 Ag-RDT results and completed 12 674 rRT-PCR tests, of which 995 (7.9%) were rRT-PCR positive. Overall sensitivity and specificity were 53.0% (95% confidence interval [CI], 49.6%–56.4%) and 98.8% (95% CI, 98.5%–99.0%), respectively. Sensitivity was comparatively higher for Ag-RDTs used 1 day after rRT-PCR (69.0%), 4–7 days after symptom onset (70.1%), and Orf1b Ct ≤20 (82.7%). Serial Ag-RDT sensitivity increased with repeat testing ≥ 2 (68.5%) and ≥ 4 (75.8%) days after an initial Ag-RDT-negative result. Conclusions Ag-RDT performance varied by clinical characteristics and temporal testing patterns. Our findings support recommendations for serial testing following an initial Ag-RDT-negative result, especially among recently symptomatic persons or those at high risk for SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

36. Local-scale phylodynamics reveal differential community impact of SARS-CoV-2 in a metropolitan US county

Author

Paredes, Miguel I., primary, Perofsky, Amanda C., additional, Frisbie, Lauren, additional, Moncla, Louise H., additional, Roychoudhury, Pavitra, additional, Xie, Hong, additional, Bakhash, Shah A. Mohamed, additional, Kong, Kevin, additional, Arnould, Isabel, additional, Nguyen, Tien V., additional, Wendm, Seffir T., additional, Hajian, Pooneh, additional, Ellis, Sean, additional, Mathias, Patrick C., additional, Greninger, Alexander L., additional, Starita, Lea M., additional, Frazar, Chris D., additional, Ryke, Erica, additional, Zhong, Weizhi, additional, Gamboa, Luis, additional, Threlkeld, Machiko, additional, Lee, Jover, additional, Stone, Jeremy, additional, McDermot, Evan, additional, Truong, Melissa, additional, Shendure, Jay, additional, Oltean, Hanna N., additional, Viboud, Cécile, additional, Chu, Helen, additional, Müller, Nicola F., additional, and Bedford, Trevor, additional

Published
2024
Full Text
View/download PDF

37. SARS-CoV-2 diversity and transmission on a university campus across two academic years during the pandemic

Author

Casto, Amanda M, primary, Paredes, Miguel I, additional, Bennett, Julia Catherine, additional, Luiten, Kyle G, additional, O'Hanlon, Jessica A., additional, Han, Peter D., additional, Gamboa, Luis, additional, McDermot, Evan, additional, Truong, Melissa, additional, Gottlieb, Geoffrey S, additional, Acker, Zack, additional, Wolf, Caitlin R, additional, Magedson, Ariana, additional, Lo, Natalie K., additional, McDonald, Devon, additional, Wright, Tessa C, additional, McCaffrey, Kathryn, additional, Figgins, Marlin D, additional, Englund, Janet A, additional, Boeckh, Michael, additional, Lockwood, Christina M, additional, Nickerson, Deborah A., additional, Shendure, Jay, additional, Uyeki, Timothy M, additional, Starita, Lea M, additional, Bedford, Trevor, additional, Chu, Helen Y, additional, and Weil, Ana A, additional

Published
2024
Full Text
View/download PDF

38. Multiplexed Functional Assessments of MYH7 Variants in Human Cardiomyocytes

Author

Friedman, Clayton E., primary, Fayer, Shawn, additional, Pendyala, Sriram, additional, Chien, Wei-Ming, additional, Loiben, Alexander, additional, Tran, Linda, additional, Chao, Leslie S., additional, McKinstry, Ashley, additional, Ahmed, Dania, additional, Farris, Stephen D., additional, Stempien-Otero, April, additional, Jonlin, Erica C., additional, Murry, Charles E., additional, Starita, Lea M., additional, Fowler, Douglas M., additional, and Yang, Kai-Chun, additional

Published
2024
Full Text
View/download PDF

39. Evidence for Limited Early Spread of COVID-19 Within the United States, January–February 2020

Author

CDC COVID-19 Response Team, Jorden, Michelle A., Rudman, Sarah L., Villarino, Elsa, Hoferka, Stacey, Patel, Megan T., Bemis, Kelley, Simmons, Cristal R., Jespersen, Megan, Johnson, Jenna Iberg, Mytty, Elizabeth, Arends, Katherine D., Henderson, Justin J., Mathes, Robert W., Weng, Charlene X., Duchin, Jeffrey, Lenahan, Jennifer, Close, Natasha, Bedford, Trevor, Boeckh, Michael, Chu, Helen Y., Englund, Janet A., Famulare, Michael, Nickerson, Deborah A., Rieder, Mark J., Shendure, Jay, and Starita, Lea M.

Published
2020

40. Variant Interpretation: Functional Assays to the Rescue

Author

Starita, Lea M, Ahituv, Nadav, Dunham, Maitreya J, Kitzman, Jacob O, Roth, Frederick P, Seelig, Georg, Shendure, Jay, and Fowler, Douglas M

Subjects
Biological Sciences, Genetics, 2.1 Biological and endogenous factors, Aetiology, Generic health relevance, Computational Biology, Disease, Genetic Variation, Genome, Human, Humans, Medical and Health Sciences, Genetics & Heredity, Biological sciences, Biomedical and clinical sciences, Health sciences
Abstract

Classical genetic approaches for interpreting variants, such as case-control or co-segregation studies, require finding many individuals with each variant. Because the overwhelming majority of variants are present in only a few living humans, this strategy has clear limits. Fully realizing the clinical potential of genetics requires that we accurately infer pathogenicity even for rare or private variation. Many computational approaches to predicting variant effects have been developed, but they can identify only a small fraction of pathogenic variants with the high confidence that is required in the clinic. Experimentally measuring a variant's functional consequences can provide clearer guidance, but individual assays performed only after the discovery of the variant are both time and resource intensive. Here, we discuss how multiplex assays of variant effect (MAVEs) can be used to measure the functional consequences of all possible variants in disease-relevant loci for a variety of molecular and cellular phenotypes. The resulting large-scale functional data can be combined with machine learning and clinical knowledge for the development of "lookup tables" of accurate pathogenicity predictions. A coordinated effort to produce, analyze, and disseminate large-scale functional data generated by multiplex assays could be essential to addressing the variant-interpretation crisis.

Published
2017

41. Multiplexed assay of variant effect reveals residues of functional importance in the BRCA1 coiled-coil and serine cluster domains

Author

Nagy, Gregory, primary, Diabate, Mariame, additional, Banerjee, Tapahsama, additional, Adamovich, Aleksandra I., additional, Smith, Nahum, additional, Jeon, Hyeongseon, additional, Dhar, Shruti, additional, Liu, Wenfang, additional, Burgess, Katherine, additional, Chung, Dongjun, additional, Starita, Lea M., additional, and Parvin, Jeffrey D., additional

Published
2023
Full Text
View/download PDF

42. Human mobility impacts the transmission of common respiratory viruses: A modeling study of the Seattle metropolitan area

Author

Perofsky, Amanda C., primary, Hansen, Chelsea, additional, Burstein, Roy, additional, Boyle, Shanda, additional, Prentice, Robin, additional, Marshall, Cooper, additional, Reinhart, David, additional, Capodanno, Ben, additional, Truong, Melissa, additional, Schwabe-Fry, Kristen, additional, Kuchta, Kayla, additional, Pfau, Brian, additional, Acker, Zack, additional, Lee, Jover, additional, Sibley, Thomas R., additional, McDermot, Evan, additional, Rodriguez-Salas, Leslie, additional, Stone, Jeremy, additional, Gamboa, Luis, additional, Han, Peter D., additional, Adler, Amanda, additional, Waghmare, Alpana, additional, Jackson, Michael L., additional, Famulare, Mike, additional, Shendure, Jay, additional, Bedford, Trevor, additional, Chu, Helen Y., additional, Englund, Janet A., additional, Starita, Lea M., additional, and Viboud, Cecile, additional

Published
2023
Full Text
View/download PDF

44. homeRNA self-blood collection by exposed close contacts enables high-frequency temporal profiling of the pre-symptomatic host immune kinetics to respiratory viral infection

Author

Lim, Fang Yun, primary, Lea, Hannah G, additional, Dostie, Ashley, additional, van Neel, Tammi, additional, Hassan, Grant, additional, Takezawa, Meg, additional, Starita, Lea M, additional, Adams, Karen, additional, Boeckh, Michael, additional, Schiffer, Joshua T, additional, Waghmare, Alpana, additional, Berthier, Erwin, additional, and Theberge, Ashleigh B, additional

Published
2023
Full Text
View/download PDF

47. Risk of Subsequent Respiratory Virus Detection After Primary Virus Detection in a Community Household Study—King County, Washington, 2019–2021.

Author

Heimonen, Jessica, Chow, Eric J, Wang, Yongzhe, Hughes, James P, Rogers, Julia, Emanuels, Anne, O'Hanlon, Jessica, Han, Peter D, Wolf, Caitlin R, Logue, Jennifer K, Ogokeh, Constance E, Rolfes, Melissa A, Uyeki, Timothy M, Starita, Lea, Englund, Janet A, and Chu, Helen Y

Subjects
SARS-CoV-2, PARAINFLUENZA viruses
Abstract

Background The epidemiology of respiratory viral infections is complex. How infection with one respiratory virus affects risk of subsequent infection with the same or another respiratory virus is not well described. Methods From October 2019 to June 2021, enrolled households completed active surveillance for acute respiratory illness (ARI), and participants with ARI self-collected nasal swab specimens; after April 2020, participants with ARI or laboratory-confirmed severe acute respiratory syndrome coronavirus 2 and their household members self-collected nasal swab specimens. Specimens were tested using multiplex reverse-transcription polymerase chain reaction for respiratory viruses. A Cox regression model with a time-dependent covariate examined risk of subsequent detections following a specific primary viral detection. Results Rhinovirus was the most frequently detected pathogen in study specimens (406 [9.5%]). Among 51 participants with multiple viral detections, rhinovirus to seasonal coronavirus (8 [14.8%]) was the most common viral detection pairing. Relative to no primary detection, there was a 1.03–2.06-fold increase in risk of subsequent virus detection in the 90 days after primary detection; risk varied by primary virus: human parainfluenza virus, rhinovirus, and respiratory syncytial virus were statistically significant. Conclusions Primary virus detection was associated with higher risk of subsequent virus detection within the first 90 days after primary detection. [ABSTRACT FROM AUTHOR]

Published
2024
Full Text
View/download PDF

49. Abstract P1019: High-throughput Generation And Functional Characterization Of Myosin Heavy Chain 7 Variants In Genome-edited Cardiomyocytes

Author

Yang, Kai-Chun, primary, Friedman, Clayton, additional, Fayer, Shawn, additional, Pendyala, Sriram, additional, Chien, Wei-Ming, additional, Loiben, Alexander, additional, Chao, Leslie, additional, Ahmed, Dania, additional, Karbassi, Elaheh, additional, Murry, Charles, additional, Starita, Lea, additional, and Fowler, Douglas, additional

Published
2023
Full Text
View/download PDF

50. Risk of Subsequent Respiratory Virus Detection After Primary Virus Detection in a Community Household Study—King County, Washington, 2019–2021

Author

Heimonen, Jessica, primary, Chow, Eric J, additional, Wang, Yongzhe, additional, Hughes, James P, additional, Rogers, Julia, additional, Emanuels, Anne, additional, O’Hanlon, Jessica, additional, Han, Peter D, additional, Wolf, Caitlin R, additional, Logue, Jennifer K, additional, Ogokeh, Constance E, additional, Rolfes, Melissa A, additional, Uyeki, Timothy M, additional, Starita, Lea, additional, Englund, Janet A, additional, and Chu, Helen Y, additional

Published
2023
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results