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  1. Article ; Online: A refined use of mutations to guide immunotherapy decisions.

    Cheng, Chao / Amos, Christopher I

    Nature

    2023  Volume 612, Issue 7941, Page(s) 639–641

    MeSH term(s) Humans ; Immunotherapy ; Neoplasms ; Mutation
    Language English
    Publishing date 2023-08-04
    Publishing country England
    Document type News ; Comment
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/d41586-022-04448-z
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  2. Article ; Online: Why does the X chromosome lag behind autosomes in GWAS findings?

    Gorlov, Ivan P / Amos, Christopher I

    PLoS genetics

    2023  Volume 19, Issue 2, Page(s) e1010472

    Abstract: The X-chromosome is among the largest human chromosomes. It differs from autosomes by a number of important features including hemizygosity in males, an almost complete inactivation of one copy in females, and unique patterns of recombination. We used ... ...

    Abstract The X-chromosome is among the largest human chromosomes. It differs from autosomes by a number of important features including hemizygosity in males, an almost complete inactivation of one copy in females, and unique patterns of recombination. We used data from the Catalog of Published Genome Wide Association Studies to compare densities of the GWAS-detected SNPs on the X-chromosome and autosomes. The density of GWAS-detected SNPs on the X-chromosome is 6-fold lower compared to the density of the GWAS-detected SNPs on autosomes. Differences between the X-chromosome and autosomes cannot be explained by differences in the overall SNP density, lower X-chromosome coverage by genotyping platforms or low call rate of X-chromosomal SNPs. Similar differences in the density of GWAS-detected SNPs were found in female-only GWASs (e.g. ovarian cancer GWASs). We hypothesized that the lower density of GWAS-detected SNPs on the X-chromosome compared to autosomes is not a result of a methodological bias, e.g. differences in coverage or call rates, but has a real underlying biological reason-a lower density of functional SNPs on the X-chromosome versus autosomes. This hypothesis is supported by the observation that (i) the overall SNP density of X-chromosome is lower compared to the SNP density on autosomes and that (ii) the density of genic SNPs on the X-chromosome is lower compared to autosomes while densities of intergenic SNPs are similar.
    MeSH term(s) Male ; Female ; Humans ; Genome-Wide Association Study ; X Chromosome ; Polymorphism, Single Nucleotide/genetics
    Language English
    Publishing date 2023-02-27
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2186725-2
    ISSN 1553-7404 ; 1553-7390
    ISSN (online) 1553-7404
    ISSN 1553-7390
    DOI 10.1371/journal.pgen.1010472
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Book: Forward time population genetics simulations

    Peng, Bo / Kimmel, Marek / Amos, Christopher I.

    methods, implementation, and applications

    2012  

    Title variant Forward-time population genetics simulations
    Author's details Bo Peng ; Marek Kimmel ; Christopher I. Amos
    Keywords Genetics, Population ; Models, Genetic ; Biological Evolution ; Computer Simulation
    Language English
    Size XXI, 234 S. : Ill., graph. Darst.
    Publisher Wiley-Blackwell
    Publishing place Hoboken, NJ
    Publishing country United States
    Document type Book
    HBZ-ID HT017178358
    ISBN 978-0-470-50348-5 ; 0-470-50348-3
    Database Catalogue ZB MED Medicine, Health

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  4. Article ; Online: A statistical learning method for simultaneous copy number estimation and subclone clustering with single-cell sequencing data.

    Qin, Fei / Cai, Guoshuai / Amos, Christopher I / Xiao, Feifei

    Genome research

    2024  Volume 34, Issue 1, Page(s) 85–93

    Abstract: The availability of single-cell sequencing (SCS) enables us to assess intra-tumor heterogeneity and identify cellular subclones without the confounding effect of mixed cells. Copy number aberrations (CNAs) have been commonly used to identify subclones in ...

    Abstract The availability of single-cell sequencing (SCS) enables us to assess intra-tumor heterogeneity and identify cellular subclones without the confounding effect of mixed cells. Copy number aberrations (CNAs) have been commonly used to identify subclones in SCS data using various clustering methods, as cells comprising a subpopulation are found to share a genetic profile. However, currently available methods may generate spurious results (e.g., falsely identified variants) in the procedure of CNA detection, thereby diminishing the accuracy of subclone identification within a large, complex cell population. In this study, we developed a subclone clustering method based on a fused lasso model, referred to as FLCNA, which can simultaneously detect CNAs in single-cell DNA sequencing (scDNA-seq) data. Spike-in simulations were conducted to evaluate the clustering and CNA detection performance of FLCNA, benchmarking it against existing copy number estimation methods (SCOPE, HMMcopy) in combination with commonly used clustering methods. Application of FLCNA to a scDNA-seq data set of breast cancer revealed different genomic variation patterns in neoadjuvant chemotherapy-treated samples and pretreated samples. We show that FLCNA is a practical and powerful method for subclone identification and CNA detection with scDNA-seq data.
    MeSH term(s) DNA Copy Number Variations ; Sequence Analysis, DNA/methods ; Base Sequence ; Cluster Analysis
    Language English
    Publishing date 2024-02-07
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.278098.123
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: Corrigendum: A statistical learning method for simultaneous copy number estimation and subclone clustering with single-cell sequencing data.

    Qin, Fei / Cai, Guoshuai / Amos, Christopher I / Xiao, Feifei

    Genome research

    2024  Volume 34, Issue 3, Page(s) 514

    Language English
    Publishing date 2024-04-25
    Publishing country United States
    Document type Journal Article ; Published Erratum
    ZDB-ID 1284872-4
    ISSN 1549-5469 ; 1088-9051 ; 1054-9803
    ISSN (online) 1549-5469
    ISSN 1088-9051 ; 1054-9803
    DOI 10.1101/gr.279293.124
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  6. Article: Predicting Chemotherapy Benefit across Different Races in Early-Stage Breast Cancer Patients Using the Oncotype DX Score.

    Shaw, Vikram R / Amos, Christopher I / Cheng, Chao

    Cancers

    2023  Volume 15, Issue 12

    Abstract: Background: Oncotype DX assay, a multigene molecular test, has been widely used to stratify relapse risk and guide chemotherapy treatment in breast cancer. However, the optimal threshold of the Oncotype DX score in predicting chemotherapy benefit and ... ...

    Abstract Background: Oncotype DX assay, a multigene molecular test, has been widely used to stratify relapse risk and guide chemotherapy treatment in breast cancer. However, the optimal threshold of the Oncotype DX score in predicting chemotherapy benefit and its racial variation has not been investigated.
    Methods: In this study, we apply a random forest survival model to the SEER-Oncotype cohort data (Surveillance, Epidemiology, and End Results with Oncotype DX test information for breast cancer patients) and determine chemotherapy benefit thresholds in early-stage, estrogen-receptor-positive (ER+), and HER2-negative (HER2-) patients of different races.
    Results: Our results indicate that early-stage ER+, HER2-, and LN-/LN+ patients may benefit from receiving chemotherapy at a lower Oncotype DX score than current guidelines (Recurrence Score, RS > 25 or RS > 30) suggest. According to the estimated chemotherapy sensitivity thresholds from our models, 2.05-2.72-fold more lymph-node-negative (LN-) and 2.08-5.02-fold more lymph-node-positive (LN+) patients who may not currently be recommended for chemotherapy by their Oncotype DX test result may actually have the potential to benefit from chemotherapy. Furthermore, our models indicate a racial difference in chemotherapy benefit: white, black, and Asian women with early-stage ER+/LN- tumors benefit from chemotherapy when their Oncotype DX scores are greater than 19.9, 37.2, and 18.0, respectively.
    Conclusions: Our study provides a method for calibrating multigene molecular tests to help guide treatment decisions in racially and ethnically diverse patients with cancer. Specifically, we identify key chemotherapy sensitivity thresholds for the Oncotype DX recurrence score test in breast cancer patients and provide evidence that certain patients may benefit from receiving chemotherapy at a lower threshold than the current clinical guidelines suggest.
    Language English
    Publishing date 2023-06-16
    Publishing country Switzerland
    Document type Journal Article
    ZDB-ID 2527080-1
    ISSN 2072-6694
    ISSN 2072-6694
    DOI 10.3390/cancers15123217
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  7. Article ; Online: Common and distinct patterns of acquired uniparental disomy and homozygous deletions between lung squamous cell carcinomas and lung adenocarcinoma.

    Tuna, Musaffe / Mills, Gordon B / Amos, Christopher I

    Neoplasia (New York, N.Y.)

    2023  Volume 45, Page(s) 100932

    Abstract: Acquired uniparental disomy (aUPD) is a chromosomal alteration that can lead to homozygosity of existing aberrations. We used data from The Cancer Genome Atlas SNP-based arrays to identify distinct and common aUPD profiles in lung adenocarcinoma (LUAD) ... ...

    Abstract Acquired uniparental disomy (aUPD) is a chromosomal alteration that can lead to homozygosity of existing aberrations. We used data from The Cancer Genome Atlas SNP-based arrays to identify distinct and common aUPD profiles in lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). Moreover, we tested relevance of aUPD for homozygous deletion (HMD), overall survival (OS), and recurrence-free survival (RFS). Overall, we found significantly higher aUPD (q = 5.34E-09) in LUSC than in LUAD. A significant portion of HMD was associated with aUPD in LUSC (24.9%) and LUAD (19.7%). We identified segmental, whole-chromosome arm and whole-chromosome aUPD, in which whole 7p arm aUPD was restricted to LUSC, while whole-chromosome 3 aUPD was observed only in LUAD, and whole-chromosome 21 aUPD was common to both LUSC and LUAD. The most frequent aUPD and HMD were observed at CDKN2A/B region in both LUAD and LUSC. In LUAD, aUPD and HMD at CDKN2A/B region were associated with shorter OS (q < 0.021 and q < 0.005), and RFS (q < 0.005 and q < 0.005), while heterozygous deletion was not associated with OS and RFS. In contrast, no association was found between aUPD at CDKN2A/B region and survival in LUSC. In LUAD, CTLA expression was significantly lower in samples with aUPD at CDKN2A/B regions than in samples without copy number and allele-based changes. Immune infiltration correlated with aUPD or HMD at CDKN2A/B, gain at HLA class I region, and aUPD at whole-chromosome q-arm or whole chromosome in LUAD, but not in LUSC. Both LUSC and LUAD have common and distinct patterns of aUPD regions with differing frequencies of occurrence and associations with outcome.
    MeSH term(s) Humans ; Uniparental Disomy/genetics ; Homozygote ; Sequence Deletion ; Adenocarcinoma of Lung/genetics ; Adenocarcinoma of Lung/pathology ; Carcinoma, Non-Small-Cell Lung/genetics ; Carcinoma, Squamous Cell/pathology ; Lung Neoplasms/pathology ; Lung/metabolism
    Language English
    Publishing date 2023-10-04
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1483840-0
    ISSN 1476-5586 ; 1522-8002
    ISSN (online) 1476-5586
    ISSN 1522-8002
    DOI 10.1016/j.neo.2023.100932
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  8. Article ; Online: Whole-chromosome arm acquired uniparental disomy in cancer development is a consequence of isochromosome formation.

    Tuna, Musaffe / Amos, Christopher I / Mills, Gordon B

    Neoplasia (New York, N.Y.)

    2022  Volume 25, Page(s) 9–17

    Abstract: Using SNP-based microarray data from The Cancer Genome Atlas (TCGA), we investigated isochromosomes (deletion of one arm and duplication of the other arm) and related acquired uniparental disomy in 12 tumor types. We observed a high frequency of ... ...

    Abstract Using SNP-based microarray data from The Cancer Genome Atlas (TCGA), we investigated isochromosomes (deletion of one arm and duplication of the other arm) and related acquired uniparental disomy in 12 tumor types. We observed a high frequency of isochromosomes (25.98%) across all type of tumors except thyroid cancers. The highest frequency of isochromosomes was found in lung squamous cell carcinoma (54.18%). Moreover, whole-chromosome arm acquired uniparental disomy (aUPD) was common in the deleted arms of isochromosomes. These data are consistent with whole-chromosome arm aUPD likely being a consequence of isochromosomes formation. Our findings implicated aUPD as occurring through error-prone DNA repair of a deleted arm or segment of a chromosome that leads to homozygosity for existing alterations. Isochromosomes were significantly more frequent in TP53 mutated samples than wild types in 6 types of tumors with loss of TP53 function potentially contributing to development of isochromosomes. Isochromosomes are common alterations in cancer, and losing one arm of a chromosome could result in duplication of the lost arm. Duplication of the remaining arm leads promulgation of the effects on any defects in the remaining allele, due to subsequent homozygosity.
    MeSH term(s) Alleles ; Humans ; Isochromosomes/genetics ; Neoplasms/genetics ; Uniparental Disomy/genetics
    Language English
    Publishing date 2022-01-19
    Publishing country United States
    Document type Journal Article
    ZDB-ID 1483840-0
    ISSN 1476-5586 ; 1522-8002
    ISSN (online) 1476-5586
    ISSN 1522-8002
    DOI 10.1016/j.neo.2021.12.009
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  9. Article ; Online: Population simulations of COVID-19 outbreaks provide tools for risk assessment and continuity planning.

    Peng, Bo / Pettit, Rowland W / Amos, Christopher I

    JAMIA open

    2021  Volume 4, Issue 3, Page(s) ooaa074

    Abstract: Objectives: We developed COVID-19 Outbreak Simulator (https://ictr.github.io/covid19-outbreak-simulator/) to quantitatively estimate the effectiveness of preventative and interventive measures to prevent and battle COVID-19 outbreaks for specific ... ...

    Abstract Objectives: We developed COVID-19 Outbreak Simulator (https://ictr.github.io/covid19-outbreak-simulator/) to quantitatively estimate the effectiveness of preventative and interventive measures to prevent and battle COVID-19 outbreaks for specific populations.
    Materials and methods: Our simulator simulates the entire course of infection and transmission of the virus among individuals in heterogeneous populations, subject to operations and influences, such as quarantine, testing, social distancing, and community infection. It provides command-line and Jupyter notebook interfaces and a plugin system for user-defined operations.
    Results: The simulator provides quantitative estimates for COVID-19 outbreaks in a variety of scenarios and assists the development of public health policies, risk-reduction operations, and emergency response plans.
    Discussion: Our simulator is powerful, flexible, and customizable, although successful applications require realistic estimation and robustness analysis of population-specific parameters.
    Conclusion: Risk assessment and continuity planning for COVID-19 outbreaks are crucial for the continued operation of many organizations. Our simulator will be continuously expanded to meet this need.
    Language English
    Publishing date 2021-01-24
    Publishing country United States
    Document type Journal Article
    ISSN 2574-2531
    ISSN (online) 2574-2531
    DOI 10.1093/jamiaopen/ooaa074
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  10. Article ; Online: Pan-cancer evaluation of gene expression and somatic alteration data for cancer prognosis prediction.

    Zheng, Xingyu / Amos, Christopher I / Frost, H Robert

    BMC cancer

    2021  Volume 21, Issue 1, Page(s) 1053

    Abstract: Background: Over the past decades, approaches for diagnosing and treating cancer have seen significant improvement. However, the variability of patient and tumor characteristics has limited progress on methods for prognosis prediction. The development ... ...

    Abstract Background: Over the past decades, approaches for diagnosing and treating cancer have seen significant improvement. However, the variability of patient and tumor characteristics has limited progress on methods for prognosis prediction. The development of high-throughput omics technologies now provides multiple approaches for characterizing tumors. Although a large number of published studies have focused on integration of multi-omics data and use of pathway-level models for cancer prognosis prediction, there still exists a gap of knowledge regarding the prognostic landscape across multi-omics data for multiple cancer types using both gene-level and pathway-level predictors.
    Methods: In this study, we systematically evaluated three often available types of omics data (gene expression, copy number variation and somatic point mutation) covering both DNA-level and RNA-level features. We evaluated the landscape of predictive performance of these three omics modalities for 33 cancer types in the TCGA using a Lasso or Group Lasso-penalized Cox model and either gene or pathway level predictors.
    Results: We constructed the prognostic landscape using three types of omics data for 33 cancer types on both the gene and pathway levels. Based on this landscape, we found that predictive performance is cancer type dependent and we also highlighted the cancer types and omics modalities that support the most accurate prognostic models. In general, models estimated on gene expression data provide the best predictive performance on either gene or pathway level and adding copy number variation or somatic point mutation data to gene expression data does not improve predictive performance, with some exceptional cohorts including low grade glioma and thyroid cancer. In general, pathway-level models have better interpretative performance, higher stability and smaller model size across multiple cancer types and omics data types relative to gene-level models.
    Conclusions: Based on this landscape and comprehensively comparison, models estimated on gene expression data provide the best predictive performance on either gene or pathway level. Pathway-level models have better interpretative performance, higher stability and smaller model size relative to gene-level models.
    MeSH term(s) Cohort Studies ; DNA Copy Number Variations ; Databases, Genetic ; Gene Expression ; Gene Expression Profiling/methods ; Humans ; Neoplasms/genetics ; Neoplasms/mortality ; Neoplasms/pathology ; Point Mutation ; Predictive Value of Tests ; Prognosis ; Proportional Hazards Models
    Language English
    Publishing date 2021-09-25
    Publishing country England
    Document type Journal Article
    ZDB-ID 2041352-X
    ISSN 1471-2407 ; 1471-2407
    ISSN (online) 1471-2407
    ISSN 1471-2407
    DOI 10.1186/s12885-021-08796-3
    Database MEDical Literature Analysis and Retrieval System OnLINE

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