Digital Commons Network^™

Alignment Between 24-H Light-Dark And Activity-Rest Rhythms Is Associated With Diabetes And Glucose Metabolism In A Nationally Representative Sample Of American Adults, Mariana G Figueiro

Faculty, Staff and Student Publications

OBJECTIVE: The alignment between environmental stimuli (e.g., dark, light) and behavior cycles (e.g., rest, activity) is an essential feature of the circadian timing system, a key contributor to metabolic health. However, no previous studies have investigated light-activity alignment in relation to glycemic control in human populations.

RESEARCH DESIGN AND METHODS: The analysis included ∼7,000 adults (aged 20-80 years) from the National Health and Nutrition Examination Survey (NHANES) (2011-2014) with actigraphy-measured, multiday, 24-h activity and light data. We used phasor analysis to derive phasor magnitude and phasor angle, which measures coupling strength and phase difference between the activity-rest and light-dark cycles, …

Pneumatosis Intestinalis In Cancer Patients Who Received Immune Checkpoint Inhibitors, Mehmet Altan, Enrico N De Toni, Helga-Paula Török, Bryan J Schneider, Anam Khan, Anusha S Thomas, Hao Chi Zhang, Mehnaz A Shafi, Yinghong Wang

Faculty, Staff and Student Publications

Purpose: Immune checkpoint inhibitor (ICI) therapy may give rise to immune-related adverse events (irAEs). Pneumatosis intestinalis (PI), or gas within the bowel wall, has very rarely been observed following ICI therapy, and its clinical significance is unclear. We described the clinical characteristics and outcomes of PI as a possible irAE in cancer patients.

Methods: We retrospectively identified 12 adult cancer patients with radiologic evidence of PI within 1 year after ICI exposure during January 2010-January 2023. Clinical characteristics, treatment, and outcomes were evaluated.

Results: The median age of our sample was 64 years. The most common cancer types were thoracic/head …

The Association Between Inflammatory Bowel Disease And All-Cause And Cause-Specific Mortality In The Uk Biobank, Shreela V Sharma, Baharak Moshiree, Erikka Loftfield, Qing Lan, Rashmi Sinha, Maki Inoue-Choi, Emily Vogtmann

Faculty, Staff and Student Publications

PURPOSE: Inflammatory bowel disease (IBD) has a rising global prevalence. However, the understanding of its impact on mortality remains inconsistent so we explored the association between IBD and all-cause and cause-specific mortality.

METHODS: This study included 502,369 participants from the UK Biobank, a large, population-based, prospective cohort study with mortality data through 2022. IBD was defined by baseline self-report or from primary care or hospital admission data. We estimated hazard ratios (HRs) and 95% confidence intervals (CIs) for all-cause and cause-specific mortality in multivariable Cox proportional hazards regression models.

RESULTS: A total of 5799 (1.2%) participants had a history of …

A Practical Method For Integrating Community Priorities In Planning And Implementing Cancer Control Programs, Patricia A Valverde

Faculty, Staff and Student Publications

PURPOSE: Community engagement is essential in effective public health programs. This paper illustrates the methods used to engage community in the development of a multi-level implementation intervention to address cancer disparities related to hereditary cancer syndromes.

METHODS: Implementation Mapping (IM), was used to guide the co-creation of an intervention. Key partners were recruited to a 13-member statewide community advisory board (CAB) representing healthcare and community-based organizations. As part of a needs assessment, a 3-round modified Delphi method with the CAB was used to identify implementation outcomes to use in later steps of IM. An anonymous online survey of a validated …

The Preventive Effect Of Glass Ionomer Cement Restorations On Secondary Caries Formation: A Systematic Review And Meta-Analysis

Faculty, Staff and Student Publications

Objective: The objective is to compare the preventive effect on secondary caries of glass ionomer cement (GIC) restorations with amalgam or resin-composite restorations.

Methods: Two independent researchers conducted a systematic search of English publications in PubMed, Web of Science, Cochrane and Scopus. They selected randomized clinical trials comparing secondary caries incidences around GIC restorations (conventional GIC or resin-modified GIC) with amalgam or resin-composite restorations. Meta-analysis of the secondary-caries incidences with risk ratio (RR) and 95% confidence interval (95% CI) as the effect measure was performed.

Results: This review included 64 studies. These studies included 8310 GIC restorations and 5857 amalgam …

A Double-Robust Test For High-Dimensional Gene Coexpression Networks Conditioning On Clinical Information

Faculty, Staff and Student Publications

It has been increasingly appealing to evaluate whether expression levels of two genes in a gene coexpression network are still dependent given samples' clinical information, in which the conditional independence test plays an essential role. For enhanced robustness regarding model assumptions, we propose a class of double-robust tests for evaluating the dependence of bivariate outcomes after controlling for known clinical information. Although the proposed test relies on the marginal density functions of bivariate outcomes given clinical information, the test remains valid as long as one of the density functions is correctly specified. Because of the closed-form variance formula, the proposed …

Shaping Policy And Practice: Analyzing The Reach Of Highly Cited And High Altmetrics Publications For Broader Impact On Physical Activity, Deborah Salvo, Rodrigo Reis, Pedro Hallal, Michael Pratt

Faculty, Staff and Student Publications

BACKGROUND: A significant gap remains between the availability of physical activity (PA) evidence-based interventions and their application in real-world settings in policy and practice areas. This study aims to describe highly cited and high altmetrics publications in PA research and explore their impact on PA policy and practice.

METHODS: Mixed-methods sequential explanatory study including the identification and description of the top highly cited and high altmetrics PA publications from the last 10 years (including study design, population, type of PA study, number of citations, and altmetrics score), and interviews with key informants regarding research dissemination and implications on PA policy …

Machine Learning To Predict Mortality For Aneurysmal Subarachnoid Hemorrhage (Asah) Using A Large Nationwide Ehr Database, Hulin Wu

Faculty, Staff and Student Publications

Aneurysmal subarachnoid hemorrhage (aSAH) develops quickly once it occurs and threatens the life of patients. We aimed to use machine learning to predict mortality for SAH patients at an early stage which can help doctors make clinical decisions. In our study, we applied different machine learning methods to an aSAH cohort extracted from a national EHR database, the Cerner Health Facts EHR database (2000-2018). The outcome of interest was in-hospital mortality, as either passing away while still in the hospital or being discharged to hospice care. Machine learning-based models were primarily evaluated by the area under the receiver operating characteristic …

Polypharmacy And Medication Fill Nonadherence In A Population-Based Sample Of Adolescent And Young Adult Cancer Survivors, 2008–2017, Christine Markham

Faculty, Staff and Student Publications

PURPOSE: We examined the association between polypharmacy-an established risk factor for nonadherence in the elderly-and medication fill nonadherence in a large national sample of adolescent and young adult cancer survivors (AYAs) in the USA.

METHODS: We pooled data (2008-2017) from the Medical Expenditure Panel Survey. We defined polypharmacy as ≥ 3 unique medications prescribed, based on self-report and pharmacy data, and medication fill nonadherence as self-reported delay or inability to obtain a necessary medication. We estimated prevalence of medication fill nonadherence among AYAs (age 18-39 years with a cancer history). We used logistic regression to estimate the association between (1) …

Biological Age Mediates The Effects Of Perceived Neighborhood Problems On Heart Failure Risk Among Black Persons, Qian Xiao

Faculty, Staff and Student Publications

OBJECTIVE: We assessed whether biological age, measured by the epigenetic clock GrimAge, mediates the association of objective and subjective neighborhood disadvantage with incident HF among Black persons.

METHODS: Participants were 1448 self-reported Black adults (mean age (standard deviation, SD) = 64.3 (5.5)) dually enrolled in two community-based cohorts in Jackson, Mississippi, the ARIC and JHS cohorts, who were free of HF as of January 1, 2000. Incident HF events leading to hospitalization through December 31, 2017, were classified using ICD-9 discharge codes of HF. Multilevel age- and sex-adjusted Cox causal mediation models were used to examine whether biological age (at …

Re-Analysis And Meta-Analysis Of Summary Statistics From Gene-Environment Interaction Studies, Shylaja Srinivasan, Fida Bacha, Steve Chernausek, Rose Gubitosi-Klug, Jasmin Divers, Catherine Pihoker, Santica M Marcovina, Alisa K Manning, Han Chen

Faculty, Staff and Student Publications

Motivation: statistics from genome-wide association studies enable many valuable downstream analyses that are more efficient than individual-level data analysis while also reducing privacy concerns. As growing sample sizes enable better-powered analysis of gene-environment interactions, there is a need for gene-environment interaction-specific methods that manipulate and use summary statistics.

Results: We introduce two tools to facilitate such analysis, with a focus on statistical models containing multiple gene-exposure and/or gene-covariate interaction terms. REGEM (RE-analysis of GEM summary statistics) uses summary statistics from a single, multi-exposure genome-wide interaction study to derive analogous sets of summary statistics with arbitrary sets of exposures and interaction …

Re: Incidence Of Sars-Cov-2 Breakthrough Infections After Vaccination In Adults: A Population-Based Survey Through 1 March 2023, Yashar Talebi, Sarah E Messiah, Harold W Kohl, Steven H Kelder, Jessica A Ross, Lindsay N Padilla, Mark Silberman, Samantha Wylie, David Lakey, Jennifer A Shuford, Stephen J Pont, Eric Boerwinkle, Michael D Swartz

Faculty, Staff and Student Publications

No abstract provided.

Mortality And Morbidity Among Individuals With Hypertension Receiving A Diuretic, Ace Inhibitor, Or Calcium Channel Blocker: A Secondary Analysis Of A Randomized Clinical Trial, Lara M Simpson

Faculty, Staff and Student Publications

IMPORTANCE: The long-term relative risk of antihypertensive treatments with regard to mortality and morbidity is not well understood.

OBJECTIVE: to determine the long-term posttrial risk of primary and secondary outcomes among trial participants who were randomized to either a thiazide-type diuretic, calcium channel blocker (CCB), or angiotensin-converting enzyme (ACE) inhibitor with up to 23 years of follow-up.

DESIGN, SETTING, AND PARTICIPANTS: This prespecified secondary analysis of the Antihypertensive and Lipid-Lowering Treatment to Prevent Heart Attack Trial (ALLHAT), a multicenter randomized, double-blind, active-controlled clinical trial, followed up with participants aged 55 years or older with a diagnosis of hypertension and at …

The Special Sauce Of The Cancer Prevention And Control Research Network: 20 Years Of Lessons Learned In Developing The Evidence Base, Building Community Capacity, And Translating Research Into Practice, Charlotte Ellis, Prajakta Adsul, Sarah A Birken, María E Fernández, Peggy A Hannon, James R Hébert, Linda K Ko, Aaron Seaman, Thuy Vu, Heather M Brandt, Rebecca S Williams

Faculty, Staff and Student Publications

PURPOSE: The Cancer Prevention and Control Research Network (CPCRN) is a national network focused on accelerating the translation of cancer prevention and control research evidence into practice through collaborative, multicenter projects in partnership with diverse communities. From 2003 to 2022, the CPCRN included 613 members.

METHODS: We: (1) characterize the extent and nature of collaborations through a bibliometric analysis of 20 years of Network publications; and (2) describe key features and functions of the CPCRN as related to organizational structure, productivity, impact, and focus on health equity, partnership development, and capacity building through analysis of 22 in-depth interviews and review …

Twenty Years Of Capacity Building Across The Cancer Prevention And Control Research Network, Peggy Hannon, Courtney Petagna, Betsy Risendal, Catherine Rohweder, Jennifer Leeman

Faculty, Staff and Student Publications

PURPOSE: to improve population health, community members need capacity (i.e., knowledge, skills, and tools) to select and implement evidence-based interventions (EBIs) to fit the needs of their local settings. Since 2002, the Centers for Disease Control and Prevention has funded the national Cancer Prevention and Control Research Network (CPCRN) to accelerate the implementation of cancer prevention and control EBIs in communities. The CPCRN has developed multiple strategies to build community members' capacity to implement EBIs. This paper describes the history of CPCRN's experience developing and lessons learned through the use of five capacity-building strategies: (1) mini-grant programs, (2) training, (3) …

Type 2 Diabetes Modifies The Association Of Cad Genomic Risk Variants With Subclinical Atherosclerosis, Xihao Li, Joshua C Bis, Chloè Sarnowski, Peitao Wu, Lawrence F Bielak, Xiuqing Guo, Nancy Heard-Costa, Gregory L Kinney, Michael C Mahaney, May E Montasser, Nicholette D Palmer, Laura M Raffield, James G Terry, Lisa R Yanek, Jessica Bon, Donald W Bowden, Jennifer A Brody, Ravindranath Duggirala, Rita R Kalyani, Leslie A Lange, Braxton D Mitchell, Jennifer A Smith, Kent D Taylor, April P Carson, Joanne E Curran, Myriam Fornage, Barry I Freedman, Stacey Gabriel, Richard A Gibbs, Namrata Gupta, Sharon L R Kardia, Brian G Kral, Zeineen Momin, Anne B Newman, Wendy S Post, Karine A Viaud-Martinez, Kendra A Young, Lewis C Becker, Alain G Bertoni, John Blangero, John J Carr, Katherine Pratte, Bruce M Psaty, Stephen S Rich, Joseph C Wu, Rajeev Malhotra, Patricia A Peyser, Alanna C Morrison, Ramachandran S Vasan, Xihong Lin, Jerome I Rotter, James B Meigs, Alisa K Manning, Paul S De Vries

Faculty, Staff and Student Publications

BACKGROUND: Individuals with type 2 diabetes (T2D) have an increased risk of coronary artery disease (CAD), but questions remain about the underlying pathology. Identifying which CAD loci are modified by T2D in the development of subclinical atherosclerosis (coronary artery calcification [CAC], carotid intima-media thickness, or carotid plaque) may improve our understanding of the mechanisms leading to the increased CAD in T2D.

METHODS: We compared the common and rare variant associations of known CAD loci from the literature on CAC, carotid intima-media thickness, and carotid plaque in up to 29 670 participants, including up to 24 157 normoglycemic controls and 5513 …

Addressing Cervical Cancer Disparities In Texas: Expansion Of A Community-Based Prevention Initiative For Medically Underserved Populations, Saul D Rivas, Monica Gasca, Lori Campos, Savanah Foster, Melissa Martin, Marian Yvette Williams-Brown, Yvette Poindexter, Belinda Reininger, Mila P Salcedo, Andrea Milbourne, Bryan Fellman, Maria E Fernandez, Ellen Baker, Rose Gowen, Susan Fisher-Hoch, Ana M Rodriguez, Jessica Milan, Monica Pippin, Kathleen M Schmeler

Faculty, Staff and Student Publications

Although cervical cancer is preventable, significant disparities exist in access to screening and prevention services. In medically underserved areas (MUAs) of Texas, these rates are 55% higher compared to the remainder of the US. In 2019, we expanded a multicomponent, comprehensive program to improve cervical cancer prevention in partnership with 13 clinics and mobile vans in MUAs of Texas. Our multicomponent intervention program consists of community education and patient navigation coupled with a training/mentoring program for local medical providers to perform diagnostic procedures and treatment for patients with abnormal screening results. Hands-on training courses to learn these skills are coupled …

Impact Of Post-Incarceration Care Engagement Interventions On Hiv Transmission Among Young Black Men Who Have Sex With Men And Their Sexual Partners: An Agent-Based Network Modeling Study, Nicholson Collier, Russell Brewer, Katrina M Schrode, Kayo Fujimoto, Nina T Harawa, John A Schneider, Aditya S Khanna

Faculty, Staff and Student Publications

BACKGROUND: Understanding the impact of incarceration on HIV transmission among Black men who have sex with men is important given their disproportionate representation among people experiencing incarceration and the potential impact of incarceration on social and sexual networks, employment, housing, and medical care. We developed an agent-based network model (ABNM) of 10,000 agents representing young Black men who have sex with men in the city of Chicago to examine the impact of varying degrees of post-incarceration care disruption and care engagement interventions following release from jail on HIV incidence.

METHODS: Exponential random graph models were used to model network formation …

Opening The Black Box Of Family-Based Treatments: An Artificial Intelligence Framework To Examine Therapeutic Alliance And Therapist Empathy, Catherine F Eubanks, Samiran Ghosh, Stacy Ryan-Pettes

Faculty, Staff and Student Publications

The evidence-based treatment (EBT) movement has primarily focused on core intervention content or treatment fidelity and has largely ignored practitioner skills to manage interpersonal process issues that emerge during treatment, especially with difficult-to-treat adolescents (delinquent, substance-using, medical non-adherence) and those of color. A chief complaint of "real world" practitioners about manualized treatments is the lack of correspondence between following a manual and managing microsocial interpersonal processes (e.g. negative affect) that arise in treating "real world clients." Although family-based EBTs share core similarities (e.g. focus on family interactions, emphasis on practitioner engagement, family involvement), most of these treatments do not have …

The Potential Predictive Value Of Cardiac Mechanics For Left Ventricular Reverse Remodelling In Dilated Cardiomyopathy, Xinwei Tao, Zhaofeng Feng, Lianggeng Gong

Faculty, Staff and Student Publications

AIMS: Left ventricular reverse remodelling (LVRR) is an important objective of optimal medical management for dilated cardiomyopathy (DCM) patients, as it is associated with favourable long-term outcomes. Cardiac magnetic resonance (CMR) can comprehensively assess cardiac structure and function. We aimed to assess the CMR parameters at baseline and investigate independent variables to predict LVRR in DCM patients.

METHODS AND RESULTS: Nighty-eight initially diagnosed DCM patients who underwent CMR and echocardiography examinations at baseline were included. CMR parameters and feature tracking (FT) based left ventricular (LV) global strain (nStrain) and nStrain indexed to LV cardiac mass index (rStrain) were measured. The …

Atypical Meningiomas With Multiple Extracranial Metastases: A Case Description, Xuan Xiao

Faculty, Staff and Student Publications

No abstract provided.

Wastewater Analysis Of Mpox Virus In A City With Low Prevalence Of Mpox Disease: An Environmental Surveillance Study, Akpevwe Amanda Ojaruega, Eric L Brown, Sara Javornik Cregeen, Jennifer Deegan, Blake M Hanson, Michael Tisza, Hector I Ocaranza, John Balliew, Anthony W Maresso, Janelle Rios, Eric Boerwinkle, Kristina D Mena, Fuqing Wu

Faculty, Staff and Student Publications

BACKGROUND: Tracking infectious diseases at the community level is challenging due to asymptomatic infections and the logistical complexities of mass surveillance. Wastewater surveillance has emerged as a valuable tool for monitoring infectious disease agents including SARS-CoV-2 and Mpox virus. However, detecting the Mpox virus in wastewater is particularly challenging due to its relatively low prevalence in the community. In this study, we aim to characterize three molecular assays for detecting and tracking the Mpox virus in wastewater from El Paso, Texas, during February and March 2023.

METHODS: In this study, a combined approach utilizing three real-time PCR assays targeting the …

Selecting Patient-Reported Outcome Measures For A Patient-Facing Technology

Faculty, Staff and Student Publications

OBJECTIVE: This article provides insight into our process and considerations for selecting patient-reported outcome measures (PROMs) designed for self-reporting symptoms and quality-of-life among breast cancer (BCA) patients undergoing oral anticancer agent treatment via a patient-facing technology (PFT) platform.

METHODS: Following established guidelines, we conducted a thorough assessment of a specific set of PROMs, comparing their content to identify the most suitable options for studying BCA patients.

RESULTS: We recommend utilizing the combination of EORTC QLQ-C30 + EORTC QLQ-BR45 as the preferred instrument, especially when developing a dedicated "breast cancer-only" application.

DISCUSSION: When developing and maintaining a dashboard for a PFT …

Virtual Reality In Simulation-Based Emergency Skills Training: A Systematic Review With A Narrative Synthesis, Antony Payton, Brendan Mcgrath, Neil Tolley, Iain Bruce

Faculty, Staff and Student Publications

OBJECTIVE: An important role is predicted for virtual reality (VR) in the future of medical education. We performed a systematic review of the literature with a narrative synthesis, to examine the current evidence for VR in simulation-based emergency skills training. We broadly define emergency skills as any clinical skill used in the emergency care of patients across all clinical settings.

METHODS: This systematic review followed the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines. The data sources accessed during this study included: PubMed, CINAHL, EMBASE, AMED, EMCARE, HMIC, BNI, PsychINFO, Medline, CENTRAL, SCOPUS, Web of Science, BIOSIS …

A Transcriptomic Taxonomy Of Mouse Brain-Wide Spinal Projecting Neurons, Cindy T J Van Velthoven, Zizhen Yao, Changkyu Lee, Zicong Zhang, Shuguang Yu, Kun Gao, Geraldine Duque Salazar, Evgenii Kegeles, Yu Zhang, Makenzie C Tomihiro, Yiming Zhang, Zhiyun Yang, Junjie Zhu, Jing Tang, Xuan Song, Ryan J Donahue, Qing Wang, Delissa Mcmillen, Michael Kunst, Ning Wang, Kimberly A Smith, Gabriel E Romero, Michelle M Frank, Alexandra Krol, Riki Kawaguchi, Daniel H Geschwind, Guoping Feng, Lisa V Goodrich, Yuanyuan Liu, Bosiljka Tasic, Hongkui Zeng, Zhigang He

Faculty, Staff and Student Publications

The brain controls nearly all bodily functions via spinal projecting neurons (SPNs) that carry command signals from the brain to the spinal cord. However, a comprehensive molecular characterization of brain-wide SPNs is still lacking. Here we transcriptionally profiled a total of 65,002 SPNs, identified 76 region-specific SPN types, and mapped these types into a companion atlas of the whole mouse brain1. This taxonomy reveals a three-component organization of SPNs: (1) molecularly homogeneous excitatory SPNs from the cortex, red nucleus and cerebellum with somatotopic spinal terminations suitable for point-to-point communication; (2) heterogeneous populations in the reticular formation with broad …

Single-Cell Analysis Of Chromatin Accessibility In The Adult Mouse Brain, Sainath Mamde, Maria Luisa Amaral, Yuelai Wang, Andre Chu, Yang Xie, Michael Miller, Jie Xu, Zhaoning Wang, Kai Zhang, Bojing Jia, Xiaomeng Hou, Lin Lin, Qian Yang, Seoyeon Lee, Bin Li, Samantha Kuan, Hanqing Liu, Jingtian Zhou, Antonio Pinto-Duarte, Jacinta Lucero, Julia Osteen, Michael Nunn, Kimberly A Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng, Zihan Wang, Jingbo Shang, M Margarita Behrens, Joseph R Ecker, Allen Wang, Sebastian Preissl, Bing Ren

Faculty, Staff and Student Publications

Recent advances in single-cell technologies have led to the discovery of thousands of brain cell types; however, our understanding of the gene regulatory programs in these cell types is far from complete1-4. Here we report a comprehensive atlas of candidate cis-regulatory DNA elements (cCREs) in the adult mouse brain, generated by analysing chromatin accessibility in 2.3 million individual brain cells from 117 anatomical dissections. The atlas includes approximately 1 million cCREs and their chromatin accessibility across 1,482 distinct brain cell populations, adding over 446,000 cCREs to the most recent such annotation in the mouse genome. The mouse brain cCREs are …

Brain-Wide Correspondence Of Neuronal Epigenomics And Distant Projections, Yan Pang, Anna Bartlett, Zihao Peng, Wubin Ding, Angeline Rivkin, Will N Lagos, Elora Williams, Cheng-Ta Lee, Paula Assakura Miyazaki, Andrew Aldridge, Qiurui Zeng, J L Angelo Salinda, Naomi Claffey, Michelle Liem, Conor Fitzpatrick, Lara Boggeman, Zizhen Yao, Kimberly A Smith, Bosiljka Tasic, Jordan Altshul, Mia A Kenworthy, Cynthia Valadon, Joseph R Nery, Rosa G Castanon, Neelakshi S Patne, Minh Vu, Mohammad Rashid, Matthew Jacobs, Tony Ito, Julia Osteen, Nora Emerson, Jasper Lee, Silvia Cho, Jon Rink, Hsiang-Hsuan Huang, António Pinto-Duartec, Bertha Dominguez, Jared B Smith, Carolyn O'Connor, Hongkui Zeng, Shengbo Chen, Kuo-Fen Lee, Eran A Mukamel, Xin Jin, M Margarita Behrens, Joseph R Ecker, Edward M Callaway

Faculty, Staff and Student Publications

Single-cell analyses parse the brain’s billions of neurons into thousands of ‘cell-type’ clusters residing in different brain structures1. Many cell types mediate their functions through targeted long-distance projections allowing interactions between specific cell types. Here we used epi-retro-seq2 to link single-cell epigenomes and cell types to long-distance projections for 33,034 neurons dissected from 32 different regions projecting to 24 different targets (225 source-to-target combinations) across the whole mouse brain. We highlight uses of these data for interrogating principles relating projection types to transcriptomics and epigenomics, and for addressing hypotheses about cell types and connections related to genetics. …

Fimap A Fast Identity-By-Descent Mapping Test For Biobank-Scale Cohorts

Faculty, Staff and Student Publications

Although genome-wide association studies (GWAS) have identified tens of thousands of genetic loci, the genetic architecture is still not fully understood for many complex traits. Most GWAS and sequencing association studies have focused on single nucleotide polymorphisms or copy number variations, including common and rare genetic variants. However, phased haplotype information is often ignored in GWAS or variant set tests for rare variants. Here we leverage the identity-by-descent (IBD) segments inferred from a random projection-based IBD detection algorithm in the mapping of genetic associations with complex traits, to develop a computationally efficient statistical test for IBD mapping in biobank-scale cohorts. …

Molecularly Defined And Spatially Resolved Cell Atlas Of The Whole Mouse Brain, Stephen W Eichhorn, Zhiyun Lei, Limor Cohen, Kimberly A Smith, Bosiljka Tasic, Zizhen Yao, Hongkui Zeng, Xiaowei Zhuang

Faculty, Staff and Student Publications

In mammalian brains, millions to billions of cells form complex interaction networks to enable a wide range of functions. The enormous diversity and intricate organization of cells have impeded our understanding of the molecular and cellular basis of brain function. Recent advances in spatially resolved single-cell transcriptomics have enabled systematic mapping of the spatial organization of molecularly defined cell types in complex tissues1-3, including several brain regions (for example, refs. 1-11). However, a comprehensive cell atlas of the whole brain is still missing. Here we imaged a panel of more than 1,100 genes in approximately 10 million cells across the …

Single-Cell Dna Methylome And 3d Multi-Omic Atlas Of The Adult Mouse Brain, Bang-An Wang, Peter Berube, Wei Tian, Mia Kenworthy, Jordan Altshul, Joseph R Nery, Huaming Chen, Rosa G Castanon, Songpeng Zu, Yang Eric Li, Jacinta Lucero, Julia K Osteen, Antonio Pinto-Duarte, Jasper Lee, Jon Rink, Silvia Cho, Nora Emerson, Michael Nunn, Carolyn O'Connor, Zhanghao Wu, Ion Stoica, Zizhen Yao, Kimberly A Smith, Bosiljka Tasic, Chongyuan Luo, Jesse R Dixon, Hongkui Zeng, Bing Ren, M Margarita Behrens, Joseph R Ecker

Faculty, Staff and Student Publications

Cytosine DNA methylation is essential in brain development and is implicated in various neurological disorders. Understanding DNA methylation diversity across the entire brain in a spatial context is fundamental for a complete molecular atlas of brain cell types and their gene regulatory landscapes. Here we used single-nucleus methylome sequencing (snmC-seq3) and multi-omic sequencing (snm3C-seq)1 technologies to generate 301,626 methylomes and 176,003 chromatin conformation–methylome joint profiles from 117 dissected regions throughout the adult mouse brain. Using iterative clustering and integrating with companion whole-brain transcriptome and chromatin accessibility datasets, we constructed a methylation-based cell taxonomy with 4,673 cell groups and 274 …