About

Masanao Yajima is a Professor of the Practice and the Director of MSSP Consulting at Boston University. He is a member of the Probability and Statistics research group. In his role, he contributes to the department through his expertise in probability and statistics, and he leads the MSSP Consulting, providing specialized consulting services. His academic and professional focus is centered on applied mathematics, with particular involvement in the areas of probability and statistics.

Research topics

• Biology
• Computational biology
• Computer Science
• Genetics
• Medicine
• Artificial Intelligence
• Data Mining
• Mathematics
• Database
• Cancer research
• Statistics
• Mathematics education
• Immunology
• Bioinformatics
• Data science
• Library science
• Psychology
• Medical education

Selected publications

• Defining mutational signatures of lung cancer-associated carcinogens through <i>in vitro</i> exposure of human airway epithelial cells

  bioRxiv (Cold Spring Harbor Laboratory) · 2026-03-09

  articleOpen access

  ABSTRACT While distinct environmental exposures imprint unique mutational signatures on cancer genomes, the specific causal patterns for many known carcinogens remain uncharacterized in relevant human tissues. To address this gap, we developed a novel, physiologically relevant system that uses a combination of airway epithelial cells and whole genome sequencing to characterize mutational patterns induced by genotoxic carcinogens associated with lung cancer. After validating the platform’s accuracy by successfully recapturing the known signature for Benzo(a)pyrene (BaP), we used this system to gain detailed insights into the types of mutations that occur with exposure to N-nitrosotris-(2-chloroethyl) urea (NTCU) and 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), genotoxic compounds that induce lung squamous cell carcinoma and lung adenocarcinoma in mouse models, respectively. Cells exposed to NTCU had significantly more somatic SNVs compared to control samples. An average of 82.3% of mutations in NTCU samples were attributed to a novel mutational signature distinct from those in the COSMIC database but highly correlated with recent in vivo mouse models. In contrast, NNK exposure did not demonstrate a distinct mutational pattern above background at both high and low concentrations. Ultimately, this in vitro system provides a robust platform to define causal links between environmental exposures and mutational patterns in lung cancer mutagenesis. Statement of Significance In vitro exposure of N-nitrosotris-(2-chloroethyl) urea to airway epithelial cells revealed a distinct mutational signature.

  PublisherOA PDFDOI

• Supplementary Data from Characterization of Mutational Signatures in Tumors from a Large Chinese Population

  2025-08-29

  preprintOpen access

  &lt;p&gt;Supplementary Data&lt;/p&gt;

  PublisherDOI

• Data from Characterization of Mutational Signatures in Tumors from a Large Chinese Population

  2025-08-29

  articleOpen access

  &lt;div&gt;Abstract&lt;p&gt;The majority of mutational signatures have been characterized in tumors from American and European countries, and the degree to which mutational signatures are similar to or different from those in Chinese populations has not been fully explored. We leveraged a large-scale clinical sequencing cohort of tumors from the Chinese population developed by OrigiMed (OM). A total of 2,115 tumors from 25 major tumor types that had at least 10 single-base substitutions (SBS) were used for mutational signature analysis. Sixteen mutational signatures from the Catalogue of Somatic Mutations in Cancer (COSMIC) database were identified in the OM cohort using the musicatk package. The activity levels for most of the signatures were similar to those in a cohort from Memorial Sloan Kettering in the United States. The activity level for the apolipoprotein B mRNA editing catalytic polypeptide-like–related signature SBS2 was significantly lower in breast tumors in the OM cohort. The aristolochic acid signature SBS22 was observed in four soft-tissue sarcomas, and the &lt;i&gt;POLE&lt;/i&gt;-associated signature SBS10 was observed in a gallbladder carcinoma. In lung adenocarcinoma, the polycyclic aromatic hydrocarbon signature SBS4 was significantly higher in males compared with females but not associated with smoking status. UV-related mutations were significantly lower in cutaneous melanomas from the Chinese cohort compared with the American cohort and may contribute to lower response rates to immunotherapy observed in this population. Overall, these results add to our understanding of the mutational processes that contribute to tumors from the Chinese population.&lt;/p&gt;Significance:&lt;p&gt;Analysis of a large Chinese cohort from 25 tumor types reveals similarities and differences in the activity of mutational signatures compared with other populations.&lt;/p&gt;&lt;/div&gt;

  PublisherDOI

• Supplementary Tables from Characterization of Mutational Signatures in Tumors from a Large Chinese Population

  2025-08-29

  supplementary-materialsOpen access

  &lt;p&gt;Supplementary Tables&lt;/p&gt;

  PublisherDOI

• Figure 3 from Characterization of Mutational Signatures in Tumors from a Large Chinese Population

  2025-08-29

  preprintOpen access

  &lt;p&gt;Comparison of signature detection and activity levels across populations. &lt;b&gt;A,&lt;/b&gt; Signatures with at least 10 counts in a tumor were considered detected in that tumor. The frequencies of detected signatures were compared across Chinese (OM) and American (MSK) cohorts using Fisher’s exact test with an FDR correction. Only tumor types with at least five tumors in each cohort were included. The majority of signature detection rates were not significantly different between cohorts, with the exception of the UV-associated signature SBS7, which was found in a higher proportion of soft-tissue sarcomas in the MSK cohort compared with the OM cohort. &lt;b&gt;B,&lt;/b&gt; The median levels of proportional signature activities were compared for matched tumor types between the Chinese (OM) and American (MSK) cohorts using a Wilcoxon rank-sum test with an FDR correction. The majority of signature activities were not significantly different between cohorts with the exception of the apolipoprotein B mRNA editing catalytic polypeptide-like SBS2 signature in breast carcinoma, the SBS6 signature in colorectal carcinoma, and the SBS5 signature in HCC.&lt;/p&gt;

  PublisherDOI

• Characterization of Mutational Signatures in Tumors from a Large Chinese Population

  Cancer Research Communications · 2025-08-01 · 3 citations

  articleOpen access

  The majority of mutational signatures have been characterized in tumors from American and European countries, and the degree to which mutational signatures are similar to or different from those in Chinese populations has not been fully explored. We leveraged a large-scale clinical sequencing cohort of tumors from the Chinese population developed by OrigiMed (OM). A total of 2,115 tumors from 25 major tumor types that had at least 10 single-base substitutions (SBS) were used for mutational signature analysis. Sixteen mutational signatures from the Catalogue of Somatic Mutations in Cancer (COSMIC) database were identified in the OM cohort using the musicatk package. The activity levels for most of the signatures were similar to those in a cohort from Memorial Sloan Kettering in the United States. The activity level for the apolipoprotein B mRNA editing catalytic polypeptide-like-related signature SBS2 was significantly lower in breast tumors in the OM cohort. The aristolochic acid signature SBS22 was observed in four soft-tissue sarcomas, and the POLE-associated signature SBS10 was observed in a gallbladder carcinoma. In lung adenocarcinoma, the polycyclic aromatic hydrocarbon signature SBS4 was significantly higher in males compared with females but not associated with smoking status. UV-related mutations were significantly lower in cutaneous melanomas from the Chinese cohort compared with the American cohort and may contribute to lower response rates to immunotherapy observed in this population. Overall, these results add to our understanding of the mutational processes that contribute to tumors from the Chinese population. SIGNIFICANCE: Analysis of a large Chinese cohort from 25 tumor types reveals similarities and differences in the activity of mutational signatures compared with other populations.

  PublisherOA PDFDOI

• An atlas of gene programs in non-small cell lung cancer delineates novel patterns of lineage vacillation, plasticity, and aggressiveness

  bioRxiv (Cold Spring Harbor Laboratory) · 2025-05-10 · 1 citations

  preprintOpen access

  Combinations of molecular programs can be altered in cancer cells and contribute to tumor initiation and aggressiveness. We developed a novel framework called a Gene Program Association Study (GPAS) to create an atlas of gene co-expression modules in cancer cells from 127 primary non-small-cell-lung cancers (NSCLCs) and determine their association with clinical and histopathological features. Lung adenocarcinoma (LUAD) displayed "lineage vacillation" defined by extensive heterogeneity of modules from different alveolar cell types. Modules associated with late-stage LUAD were found in cells from early-stage tumors suggesting that aggressive phenotypes can be observed before clinical progression. Basal- and squamous-like intermediate cells were observed in the transition to invasive mucinous LUAD. In lung squamous cell carcinoma, a novel subtype was identified with lower levels of canonical squamous modules and higher levels of fibrinogen. Overall, this atlas elucidated the combinations of molecular programs in cancer cells that contribute to heterogeneity and aggressiveness in NSCLC. Statement of Significance: We performed a Gene Program Association Study (GPAS) to create an atlas of gene modules in cancer cells from NSCLCs. This atlas revealed extensive lineage vacillation, combinations of modules that defined late-stage disease, novel routes of lineage plasticity, and novel subtypes in lung adenocarcinoma or lung squamous cell carcinoma.

  PublisherOA PDFDOI

• Insights, opportunities, and challenges provided by large cell atlases

  Genome biology · 2025-10-20 · 7 citations

  reviewOpen access

  The field of single-cell biology is growing rapidly, generating large amounts of data from a variety of species, disease conditions, tissues, and organs. Coordinated efforts such as CZI CELLxGENE, HuBMAP, Broad Institute Single Cell Portal, and DISCO allow researchers to access large volumes of curated datasets, including more than just scRNA-seq data. These resources have created an opportunity to build and expand the computational biology ecosystem to develop tools necessary for data reuse and for extracting novel biological insights. We highlight achievements made so far, areas where further development is needed, and specific challenges that need to be overcome.

  PublisherDOI

• Figure 4 from Characterization of Mutational Signatures in Tumors from a Large Chinese Population

  2025-08-29

  preprintOpen access

  &lt;p&gt;SBS4 activity associated with sex but not smoking status in LUAD. &lt;b&gt;A,&lt;/b&gt; SBS4 activity was predominantly observed in lung cancers, including LUAD, LUSC, and SCLC. Each stacked bar represents the estimated activity levels of each signature in each tumor. Signatures with no estimated activity in these tumor types were excluded. &lt;b&gt;B,&lt;/b&gt; SBS4 activity was compared between three major types of lung cancer using the Wilcoxon rank-sum test. LUAD had significantly lower SBS4 activity than LUSC. &lt;b&gt;C,&lt;/b&gt; The relationship between smoking status, sex, and &lt;i&gt;EGFR&lt;/i&gt; mutation status is shown for a subset of LUADs with complete clinical information (&lt;i&gt;n&lt;/i&gt; = 271). A higher proportion of males were observed in smokers compared with nonsmokers, and a higher proportion of &lt;i&gt;EGFR&lt;/i&gt; mutations were observed in females compared with males in both smokers and nonsmokers. &lt;b&gt;D,&lt;/b&gt; Using a Wilcoxon rank-sum test, SBS4 activity was significantly higher in males compared with females in both smokers and nonsmokers but was not significantly different between smokers and nonsmokers within males or within females. &lt;b&gt;E,&lt;/b&gt; Using a multivariate linear model, SBS4 activity was associated with sex, sample type (i.e., lower in metastasis compared with primary), &lt;i&gt;EGFR&lt;/i&gt; mutation status, and age. CI, confidence interval.&lt;/p&gt;

  PublisherDOI

• Figure 1 from Characterization of Mutational Signatures in Tumors from a Large Chinese Population

  2025-08-29

  preprintOpen access

  &lt;p&gt;The landscape of highly active mutational signatures in a large Chinese population. Sixteen mutational signatures were identified across 2,115 tumors from 25 tumor types. The size of the dot corresponds to the percentage of tumors within each tumor type that have detectable levels of the signature. Signatures with at least 10 counts were considered detected in an individual tumor. The color of the dot corresponds to the median activity of each signature within the detected samples per megabase (Mb).&lt;/p&gt;

  PublisherDOI

Recent grants

• Integrative clustering of cells and samples using multi-modal single-cell data

  NIH · $1.1M · 2019–2024

Frequent coauthors

• Joshua D. Campbell

  Boston Medical Center

  22 shared

• Raphaël Gottardo

  16 shared

• Peter S. Linsley

  14 shared

• Vivian H. Gersuk

  Benaroya Research Institute

  12 shared

• Shiyi Yang

  12 shared

• Valentin Voillet

  10 shared

• W. Evan Johnson

  Rutgers New Jersey Medical School

  10 shared

• Aaron Chevalier

  9 shared

Education

• PhD, Statistics

  University of California Los Angeles

  2013