Publications

2025

1. MSIanalyzer: Targeted Nanopore Sequencing Enables Single Nucleotide Resolution Analysis of Microsatellite Instability Diversity

   Ting Zhai, Daniel J. Laverty, and Zachary D. Nagel

   bioRxiv, 2025

   Abs DOI

   We present a targeted sequencing-based pipeline that profiles microsatellite instability (MSI) at single-nucleotide resolution. Targeted amplicons from the five widely studied Bethesda panel microsatellite loci were sequenced using Oxford Nanopore Technology in two microsatellite unstable colorectal cancer cell lines (HCT15, HCT116), two microsatellite stable cancer cell lines (TK6, U2OS), and two peripheral blood mononuclear cell samples from healthy donors. An anchor-extension algorithm was developed to capture repeat motifs while allowing interruptions, using a threshold informed by platform-specific error. Cluster-aware Dirichlet-multinomial and beta-binomial tests were applied for between-sample comparisons while accounting for read-level clustering within samples. The algorithm revealed distinct repeat profiles in HCT15 and HCT116 compared to other cell types and uncovered allelic diversity across samples at different MSI loci. Our approach complements existing short tandem repeat callers by preserving read-level diversity and delivering targeted, quantitative MSI calls with potential applications in mechanistic research and clinical assay development.

2. Comprehensive Measurement of Inter-Individual Variation in DNA Repair Capacity in Healthy Individuals

   Ting Zhai, Patrizia Mazzucato, Catherine Ricciardi, David C. Christiani, Liming Liang, Leona D. Samson, Isaac A. Chaim, and Zachary D. Nagel

   medRxiv, 2025

   Abs DOI

   Rare genetic DNA repair deficiency syndromes can lead to immunodeficiency, neurological disorders, and cancer. In the general population, inter-individual variation in DNA repair capacity (DRC) influences susceptibility to cancer and several age-related diseases. Genome wide association studies and functional analyses show that defects in multiple DNA repair pathways jointly increase disease risk, but previous technologies did not permit comprehensive analyses of DNA repair in populations. To overcome these limitations, we used fluorescence multiplex host cell reactivation (FM-HCR) assays that directly quantify DRC across six major DNA repair pathways. We assessed DRC in phytohemagglutinin-stimulated primary lymphocytes from 56 healthy individuals and validated assay reproducibility in 10 individuals with up to five independent blood draws. We furthermore developed generalized analytical pipelines for systematically adjusting for batch effects and both experimental and biological confounders. Our results reveal significant inter-individual variation in DRC for each of 10 reporter assays that measure the efficiency of distinct repair processes. Our data also demonstrate that correlations between the activities of different DNA repair pathways are relatively weak. This finding suggests that each pathway may independently influence susceptibility to the health effects of DNA damage. We furthermore developed a pipeline for analyzing comet repair kinetics and related our new functional data to previously reported comet assay data for the same individuals. Our pioneering analysis underscores the sensitivity of FM-HCR assays for detecting subtle biological differences between individuals and establishes standardized methodologies for population studies. Our findings and open source analytical tools advance precision medicine by enabling comprehensive exploration of genetic, demographic, clinical, and lifestyle factors and supporting targeted interventions to enhance DNA repair and maintain genomic integrity, thereby promoting personalized healthcare and disease prevention.

3. Residual Volume and Total Lung Capacity at Diagnosis Predict Overall Survival in Non‐Small Cell Lung Cancer Patients

   Ting Zhai, Yi Li, Robert Brown, Michael Lanuti, Justin F. Gainor, and David C. Christiani

   Cancer Medicine, 2025

   Abs DOI

   Lung volume as a part of pulmonary function test, is often underrepresented in prognostic lung cancer research. In this longitudinal lung cancer survivor cohort, higher residual volume to total lung capacity (RV/TLC) ratio upon diagnosis was associated with worse overall survival regardless of spirometry results or cancer stage. The findings provide first-line evidence for the prognostic value of lung volume measurements, and lay the groundwork for future studies to clarify their role in lung cancer prognosis.

2024

1. Current technologies for measuring or predicting telomere length from genomic datasets

   Ting Zhai, and Zachary D. Nagel

   2024

   DOI

2023

1. Annual space weather fluctuations and telomere length in the Normative Aging Study

   Ting Zhai, Carolina L. Zilli Vieira, Pantel Vokonas, Andrea A. Baccarelli, Zachary D. Nagel, Joel Schwartz, and Petros Koutrakis

   Journal of Exposure Science & Environmental Epidemiology, 2023

   Abs DOI

   Galactic cosmic rays may accelerate the aging process in populations on the Earth, despite the protection by the Earth’s atmosphere and magnetic field. This research enhances our understanding of how changes in space weather can impact health, highlights potential risks from space to Earth inhabitants, and helps inform health strategies for vulnerable populations.

2022

1. Early natural menopause is associated with poor lung health and increased mortality among female smokers

   Ting Zhai, Brenda Diergaarde, David O. Wilson, Huining Kang, Akshay Sood, Samuel H. Bayliss, Jian-Min Yuan, Maria A. Picchi, Qing Lan, Steven A. Belinsky, Jill M. Siegfried, Linda S. Cook, and Shuguang Leng

   American Journal of Obstetrics & Gynecology, 2022

   Abs DOI

   Cigarette smoking is the most harmful factor for lung health. Early natural menopause is a biomarker of reproductive and somatic aging. Understanding the effect of early menopause on health outcomes in middle-aged and older female smokers is important to develop preventive strategies. Early natural menopause was associated with worse lung health, accelerated lung aging, and higher all-cause and respiratory mortality. Females with early natural menopause who continued smoking had a dramatically (>4.5-fold) increased risk of lung cancer (LC) and cancer-specific mortality. The effects of early menopause on lung health and aging sequela were rarely studied in female smokers. This study has provided strong evidence supporting the importance of maintaining lung health in female smokers with early natural menopause. Moreover, female smokers with early natural menopause should be targeted for smoking cessation and LC screening.

2. Spirometry at Diagnosis and Overall Survival in Non-Small Cell Lung Cancer Patients

   Ting Zhai, Yi Li, Robert Brown, Michael Lanuti, Justin F. Gainor, and David C. Christiani

   Cancer Medicine, 2022

   Abs DOI

   Pulmonary function can predict all-cause mortality, and chronic obstructive pulmonary disease (COPD) is associated with worse overall survival (OS) in non-small cell lung cancer (NSCLC) patients. Though pre-operative lung function is predictive of in-hospital mortality following lung cancer surgery, its predictive utility for long-term survival is unclear. The prognostic role of commonly used spirometry tests in survival of lung cancer also remains uncertain. This study evaluates the role of spirometry at lung cancer diagnosis in predicting OS of NSCLC patients. This was a retrospective study using data from the Boston Lung Cancer Study on newly diagnosed NSCLC patients with spirometry tests performed before cancer therapy (n = 2805). Spirometric test values, after being categorized using quartiles, were analyzed for association with OS using univariate and risk-adjusted multiple regression models. Further, we analyzed OS by the status of COPD determined by spirometry, and, among those with COPD, by its stage defined by the Global Initiative for Chronic Obstructive Lung Disease criteria. Both univariate and multiple regression models demonstrated that lower quartiles of actual and percent predicted forced expiratory volume in 1 second and forced vital capacity at lung cancer diagnosis were significantly associated with worse OS. Spirometry-determined COPD, and more advanced stage of COPD at lung cancer diagnosis were associated with worse lung cancer OS. The findings provide evidence that a good pulmonary function at diagnosis may help improve OS in NSCLC patients.

3. Wood smoke exposure affects lung aging, quality of life, and all-cause mortality in New Mexican smokers

   Shuguang Leng, Maria A. Picchi, Paula M. Meek, Menghui Jiang, Samuel H. Bayliss, Ting Zhai, Ruslan I. Bayliyev, Yohannes Tesfaigzi, Matthew J. Campen, Huining Kang, Yiliang Zhu, Qing Lan, Akshay Sood, and Steven A. Belinsky

   Respiratory Research, 2022

   DOI

2020

1. Changes in Bone Metabolism After Sleeve Gastrectomy Versus Gastric Bypass: a Meta-Analysis

   Zhao Tian, XinTong Fan, ShiZhen Li, Ting Zhai, and Jing Dong

   Obesity Surgery, 2020

   DOI

2018

1. Ghrelin receptor is required for the effects of nesfatin-1 on glucose metabolism

   Xin-Tong Fan, Zhao Tian, Shi-Zhen Li, Ting Zhai, Jun-Li Liu, Rui Wang, Cai-Shun Zhang, Liu-Xin Wang, Jun-Hua Yuan, Yu Zhou, and Jing Dong

   Frontiers in Endocrinology (Lausanne), 2018

   Co-first authorship

   DOI
2. Potential Micronutrients and Phytochemicals against Pathogenesis of Chronic Obstructive Pulmonary Disease and Lung Cancer

   Ting Zhai, Shizhen Li, Wei Hu, Duo Li, and Shuguang Leng

   Nutrients, 2018

   DOI

2017

1. Circulating Nesfatin-1 Levels and Type 2 Diabetes: A Systematic Review and Meta-Analysis

   Ting Zhai, Shizhen Li, XinTong Fan, Zhao Tian, XiaoQing Lu, and Jing Dong

   Journal of Diabetes Research, 2017

   DOI