January 2019

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Chen Group Newsletter | January 2019

Welcome to the January 2018 edition of the Chen Group Newsletter. This newsletter is where you can find the most relevant team and Center-wide updates, news, and highlights. 

Upcoming Events | Recent & Upcoming Presentations | Publications | Team Updates | Center Updates

Author: Eline Appelmans

Upcoming Events

January 15th, 2019 Kira Mori presenting on Chen Group Role in Adolescent HIV Prevention and Treatment Implementation Science Alliance

January 22nd, 2019 Jean De Dieu Tapsoba presenting

January 29th, 2019 Sayan Dasgupta presenting

 

We are in the process of scheduling presenters for Q1 & start of Q2 of 2019 and are interested in hearing about both the big picture ideas in infectious disease biostatistics, bioinformatics, and epidemiology methods, as well as hands-on/technical details about your feild of expertise. If you are interested in presenting at one of our team meetings or seminars please contact the group’s project manager, Elly Appelmans.

New Year 2019
https://pxhere.com/en/photo/1081286

Recent & Upcoming Conference Presentations 

Kira Mori:  Adolescent HIV Prevention and Treatment Implementation Science Alliance Forum in Kampala, Uganda, February 6th- 8th


Publications


Kapadia SN,Wu C,Mayer KH,Wilkin TJ,Amico KR,Landovitz RJ,Andrade A,Chen YQ,Chege W,McCauley M,Gulick RM,Schackman BR. (2018). No change in health-related quality of life for at-risk U.S. women and men starting HIV pre-exposure prophylaxis (PrEP): Findings from HPTN 069/ACTG A5305. PLoS One, 13(12), e0206577.
PubMed Record: https://www.ncbi.nlm.nih.gov/pubmed/30586364/?otool=fhcrclib
Abstract: INTRODUCTION: Tenofovir (TDF)-containing PrEP is effective for HIV prevention, but its effect on health-related quality of life (QOL) is unknown. Using data from HPTN 069/ACTG A5305, a randomized study of potential PrEP regimens comparing maraviroc alone, or together with TDF or emtricitabine (FTC), to TDF + FTC (control), we evaluated the impact of these regimens on QOL in at-risk HIV-uninfected U.S. women and men. METHODS: QOL was measured at baseline (before starting medications) and every 8 weeks through week 48 using the EQ-5D-3L. Responses were converted to a scale from 0.0 (death) to 1.0 (perfect health), using published valuation weights. Mean scores were compared between groups at each time point using nonparametric testing. Multivariable linear regression was used to adjust for potential confounders. RESULTS: We analyzed 186 women (median age 35 years, 65% black, 17% Hispanic) and 405 men (median age 30 years, 28% black, 22% Hispanic), including 9 transgender participants analyzed based on sex-at-birth. Mean baseline QOL was 0.91 for women and 0.95 for men. There were minimal changes in mean QOL over time for any regimen (women: p = 0.29; men: p = 0.14). There were no significant differences between participants who continued the regimen compared to participants who discontinued early (women: p = 0.61; men: p = 0.1). Mean QOL did not differ significantly by regimen at any time point, both unadjusted and after adjustment for age, race/ethnicity, adherence, and use of alcohol, marijuana, opiates, and other substances. CONCLUSIONS: QOL in at-risk individuals starting candidate PrEP regimens in a clinical trial is similar to the general population and maintained over time. This finding did not vary among regimens or when adjusted for demographics, adherence, and substance use. Our findings are the first to show that starting a candidate PrEP regimen in at-risk HIV-uninfected U.S. women and men was not associated with significant changes in QOL. TRIAL REGISTRATION: Clinicaltrials.gov NCT01505114.  

McGowan I,Wilkin T,Landovitz RJ,Wu C,Chen Y,Marzinke MA,Hendrix CW,Richardson P,Eshleman SH,Andrade A,Chege W,Anderson PL,McCauley M,Farley J,Mayer KH,Anton P,Brand RM,Cranston RD,Gulick R. (2019). The pharmacokinetics, pharmacodynamics, and mucosal responses to maraviroc-containing pre-exposure prophylaxis regimens in MSM. Aids, 33(2), 237-246.
PubMed Record: https://www.ncbi.nlm.nih.gov/pubmed/30557160/?otool=fhcrclib  
Abstract: OBJECTIVE: HIV Prevention Trials Network 069/AIDS Clinical Trials Group A5305 was a study of 48-week oral pre-exposure prophylaxis (PrEP) regimens in MSM and transgender women. A rectal substudy was included to evaluate drug concentrations in rectal compartment vs. blood, gut-associated lymphoid tissue (GALT) responses to four antiretroviral PrEP regimens [maraviroc (MVC), MVC + emtricitabine (FTC), MVC + tenofovir (TFV) disoproxil fumarate, and TFV disoproxil fumarate + FTC], and to determine whether ARV exposure was associated with ex-vivo suppression of HIV infection in colorectal explants. METHODS: C-C chemokine receptor type 5 (CCR5) genotype was characterized using PCR. At baseline and at Weeks 24, 48, and 49, GALT phenotype was characterized by flow cytometry, rectal biopsies were challenged with HIV-1BaL, and tissue and plasma pharmacokinetics were measured via mass spectrometry. RESULTS: Exposure to MVC was not associated with increased expression of CD4/CCR5 HIV target T cells. Significant ex-vivo viral suppression compared with baseline was seen at Weeks 24 and 48, ranging from 1.4 to 1.8 log10 for all study regimens except the MVC-alone arm which did not show statistically significant viral suppression at Week 48. Tissue concentrations of TFV, TFV-diphosphate, and FTC were correlated with viral suppression. CONCLUSION: MVC-containing HIV PrEP regimens did not increase GALT CD4 T-cell activation or the CD4/CCR5 phenotype. No virologic suppression was seen with MVC-alone at Week 48 compared with combination regimens, suggesting MVC monotherapy might be less effective than combination antiretroviral PrEP regimens.
 

Rose R,Hall M,Redd AD,Lamers S,Barbier AE,Porcella SF,Hudelson SE,Piwowar-Manning E,McCauley M,Gamble T,Wilson EA,Kumwenda J,Hosseinipour MC,Hakim JG,Kumarasamy N,Chariyalertsak S,Pilotto JH,Grinsztejn B,Mills LA,Makhema J,Santos BR,Chen YQ,Quinn TC,Fraser C,Cohen MS,Eshleman SH,Laeyendecker O. (2018). Phylogenetic methods inconsistently predict direction of HIV transmission among heterosexual pairs in the HPTN052 cohort. J Infect Dis.
PubMed Record: https://www.ncbi.nlm.nih.gov/pubmed/30590741/?otool=fhcrclib  
Abstract: Background: We evaluated use of phylogenetic methods to predict the direction of HIV transmission. Methods: For 33 index-partner pairs with genetically-linked infection, samples were collected from partners and indexes close to time of partners' seroconversion (SC); 31 indexes also had an earlier sample. Phylogenies were inferred using env next-generation sequences (one tree per pair/subtype). Direction of transmission (DoT) predicted from each tree was classified as correct or incorrect based on which sequences (index or partner) were closest to the root. DoT was also assessed using maximum-parsimony to infer ancestral node states for 100 bootstrap trees. Results: DoT was predicted correctly for both single pair and subtype-specific trees in 22 pairs (67%) using SC samples and 23 pairs (74%) using early index samples. DoT was predicted incorrectly for four pairs (15%) using SC or early index samples. In the bootstrap analysis, DoT was predicted correctly for 18 pairs (55%) using SC samples and 24 pairs (73%) using early index samples. DoT was predicted incorrectly for seven pairs (21%) using SC samples and four pairs (13%) using early index samples. Conclusions: Phylogenetic methods based solely on tree topology of HIV env sequences, particularly without consideration of phylogenetic uncertainty, may be insufficient for determining DoT.
 


Team Updates

Grant Submitted: Methods for Complex Longitudinal Data in HIV/AIDS Prevention Research

Grant Submitted: Methods for Complex Longitudinal Data in HIV/AIDS Prevention Research

PI: Ying Chen. Expect more news April 2019.

Submitted to PA-18-484


Center Updates

Who is The Coop?

The Coop is a cooperative that includes all groups and individuals at Fred Hutch interested in bioinformatics and data science. The problems we are trying to solve include duplication of effort, wasted resources including time and money, lack of shared knowledge and best practices, and lost collaboration opportunities.

The Coop Goals

  • Increase communication and share knowledge and expertise across the many efforts already happening
  • Provide a single point of contact for faculty and staff, external collaborators and internal researchers to engage in data-intensive research and analysis
  • Unite the Bioinformatics and Data Science Groups at Fred Hutch

 

Relevant Groups

Bioinformatics and Data Science Groups at Fred Hutch

One of The Coop's goals is to unite the the Bioinformatics and Data Science Groups at Fred Hutch. The list below is a work in progress. Please email us if you have additions, edits, or concerns.

Fred Hutch Bioinformatics Interest Group (FHBig)

The Fred Hutch Bioinformatics Interest Group (FHBig) was created by staff who perform hands-on bioinformatics and data analysis at the Fred Hutch or are interested in learning. The purpose of this group is to exchange knowledge, support each other and improve collaboration and innovation across different groups at the Hutch.

Contact: Join the FHBig Slack workspace

 

Biomedical Data Science Wiki Project

The Biomedical Data Science Wiki Project supports communication of Fred Hutch data science resources by engaging researchers and staff to collaboratively curate documentation about data management tools.

ContactAmy Pagurigan

 

fredhutch.io

fredhutch.io is an initiative to facilitate education about and promote access to computational resources at Fred Hutch

Contact: Kate Hertweck

 

Bioinformatics - Shared Resources

The Bioinformatics Shared Resource is staffed by three dedicated bioinformatics specialists available to assist researchers with processing, exploring, and understanding genomics data.

Contact: bioinformatics@fredhutch.org

 

Public Health Sciences (PHS) Herbold Computational Biology Program

The Herbold Computational Biology Program at Fred Hutch was established to bring a new generation of biological researchers to the Hutch whose training in biology is accompanied by advanced training in quantitative sciences, including physics, statistics, mathematics and computer science.

Contact: Melissa Alvendia

 

Scientific Computing (SciComp)

The Scientific Computing (SciComp) team supports Fred Hutch's science teams by providing support, training and consulting for high-performance computing, scientific software support, cloud computing(AWS, Azure), Unix database services, scientific data management and Linux desktop support.

Contact: Help Desk

 

Hutch Data Commonwealth (HDC)

The Fred Hutch Data Commonwealth (HDC) is a transformative initiative aimed at enabling investigators to leverage all possible data to eliminate disease by driving the development of data infrastructure and data science capabilities through collaborative research and robust engineering.

Contact: Carly Strasser

 

SCHARP

The Statistical Center for HIV/AIDS Research and Prevention (SCHARP) at Fred Hutch provides statistical support and data management to researchers worldwide in the fight against HIV/AIDS. The SCHARP group consists of approximately 120 staff collectively that are skilled in clinical and lab data management, programming, statistics, IT data systems, quality assurance and project management.

Contact: Jennifer Adams, Administrative Manager

Seattle Translational Tumor Research (STTR)

Seattle Translational Tumor Research (STTR) bring together experts across more than fifteen blood, lymphatic and solid tumors – bladder, brain, breast, colorectal, head & neck, leukemia, lymphoma, lung, myelodysplastic/myeloproliferative disease, myeloma, ovary, pancreas, prostate and sarcoma.

Contact: Rachel Galbraith

 

Genomics - Shared Resources

The Scientific Computing (SciComp) team supports Fred Hutch's science teams by providing support, training and consulting for high-performance computing, scientific software support, cloud computing(AWS, Azure), Unix database services, scientific data management and Linux desktop support.

Contact: genomics@fredhutch.org

 

Clinical Research Division (CRD) Clinical Biostatistics

Faculty and staff in the Clinical Biostatistics group perform methodological and collaborative biostatistical research. The collaborative work takes place with investigators within the Clinical Research Division (CRD) at Fred Hutch as well as with other investigators within the Fred Hutch/ UW Cancer Consortium

Vaccine and Infectious Disease Division (VIDD) Biostatistics

The faculty who specialize in biostatistics research aim to: 1) conduct research in statistical methodology for the design and analysis of clinical, epidemiological and basic science studies; and 2) conduct research into biologically based mathematical models for pathogenesis. 

Computational Biology Postdoc & Graduate Student Group

The Comp Bio Postdoc and Grad Student Group is self-governed and designed to facilitate collaboration and community amongst postdocs and graduate students at the Hutch that have an interest in Computational Biology.  The bimonthly meeting gives postdocs and graduate students a great opportunity to practice an upcoming talk, go over personal or lab research, discuss new technology that is being used in lab or field, discuss a journal or research question, or come up with a social activity.

Contact: Samantha Distel

 

Girls Who Code

Girls Who Code is currently enrolling girls in grades 10 through 12. The Hutch club will meet throughout the academic year every Tuesday from 4:00pm to 6:00pm. We encourage all interested in learning basic programming skills and building awesome creative projects to apply

Contact: Sarah Hilton