Publications by authors named "Zhihao Tan"

8 Publications

  • Page 1 of 1

UrbanMotion: Visual Analysis of Metropolitan-Scale Sparse Trajectories.

IEEE Trans Vis Comput Graph 2020 May 4;PP. Epub 2020 May 4.

Visualizing massive scale human movement in cities plays an important role in solving many of the problems that modern cities face (e.g., traffic optimization, business site configuration). In this work, we study a big mobile location dataset that covers millions of city residents, but is temporally sparse on the trajectory of individual user. Mapping sparse trajectories to illustrate population movement poses several challenges from both analysis and visualization perspectives. In the literature, there are a few techniques designed for sparse trajectory visualization; yet they do not consider trajectories collected from mobile apps that possess long-tailed sparsity with record intervals as long as hours. This work introduces UrbanMotion, a visual analytics system that extends the original wind map design by supporting map-matched local movements, multi-directional population flows, and population distributions. Effective methods are proposed to extract and aggregate population movements from dense parts of the trajectories leveraging their long-tailed sparsity. Both characteristic and anomalous patterns are discovered and visualized. We conducted three case studies, one comparative experiment, and collected expert feedback in the application domains of commuting analysis, event detection, and business site configuration. The result demonstrates significance and effectiveness of our system in completing key analytics tasks for urban users.
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http://dx.doi.org/10.1109/TVCG.2020.2992200DOI Listing
May 2020

Environmental stresses induce karyotypic instability in colorectal cancer cells.

Mol Biol Cell 2019 01 31;30(1):42-55. Epub 2018 Oct 31.

Institute of Medical Biology, Singapore 138648, Republic of Singapore.

Understanding how cells acquire genetic mutations is a fundamental biological question with implications for many different areas of biomedical research, ranging from tumor evolution to drug resistance. While karyotypic heterogeneity is a hallmark of cancer cells, few mutations causing chromosome instability have been identified in cancer genomes, suggesting a nongenetic origin of this phenomenon. We found that in vitro exposure of karyotypically stable human colorectal cancer cell lines to environmental stress conditions triggered a wide variety of chromosomal changes and karyotypic heterogeneity. At the molecular level, hyperthermia induced polyploidization by perturbing centrosome function, preventing chromosome segregation, and attenuating the spindle assembly checkpoint. The combination of these effects resulted in mitotic exit without chromosome segregation. Finally, heat-induced tetraploid cells were on the average more resistant to chemotherapeutic agents. Our studies suggest that environmental perturbations promote karyotypic heterogeneity and could contribute to the emergence of drug resistance.
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http://dx.doi.org/10.1091/mbc.E18-10-0626DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6337910PMC
January 2019

Mammalian Cells Undergo Endoreduplication in Response to Lactic Acidosis.

Sci Rep 2018 02 13;8(1):2890. Epub 2018 Feb 13.

Institute of Medical Biology, Agency for Science, Technology and Research (A*STAR), Singapore, Singapore.

Polyploidization, a common event during the evolution of different tumours, has been proposed to confer selective advantages to tumour cells by increasing the occurrence of mutations promoting cancer progression and by conferring chemotherapy resistance. While conditions leading to polyploidy in cancer cells have been described, a general mechanism explaining the incidence of this karyotypic change in tumours is still missing. In this study, we tested whether a widespread tumour microenvironmental condition, low pH, could induce polyploidization in mammalian cells. We found that an acidic microenvironment, in the range of what is commonly observed in tumours, together with the addition of lactic acid, induced polyploidization in transformed and non-transformed human cell lines in vitro. In addition, we provide evidence that polyploidization was mainly driven through the process of endoreduplication, i.e. the complete skipping of mitosis in-between two S-phases. These findings suggest that acidic environments, which characterize solid tumours, are a plausible path leading to polyploidization of cancer cells.
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http://dx.doi.org/10.1038/s41598-018-20186-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5811548PMC
February 2018

Transcriptional Profiling of Biofilm Regulators Identified by an Overexpression Screen in .

G3 (Bethesda) 2017 08 7;7(8):2845-2854. Epub 2017 Aug 7.

Pacific Northwest Research Institute, Seattle, Washington 98122

Biofilm formation by microorganisms is a major cause of recurring infections and removal of biofilms has proven to be extremely difficult given their inherent drug resistance . Understanding the biological processes that underlie biofilm formation is thus extremely important and could lead to the development of more effective drug therapies, resulting in better infection outcomes. Using the yeast as a biofilm model, overexpression screens identified , , , , , and as regulators of biofilm formation. Subsequent RNA-seq analysis of biofilm and nonbiofilm-forming strains revealed that all of the overexpression strains, other than and , were adopting a single differential expression profile, although induced to varying degrees. adopted a separate profile, while the expression profile of reflected the common pattern seen in most of the strains, plus substantial -specific expression changes. We interpret the existence of the common transcriptional pattern seen across multiple, unrelated overexpression strains as reflecting a transcriptional state, that the yeast cell can access through regulatory signaling mechanisms, allowing an adaptive morphological change between biofilm-forming and nonbiofilm states.
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http://dx.doi.org/10.1534/g3.117.042440DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5555487PMC
August 2017

Dissecting Gene Expression Changes Accompanying a Ploidy-Based Phenotypic Switch.

G3 (Bethesda) 2017 01 5;7(1):233-246. Epub 2017 Jan 5.

Pacific Northwest Research Institute, Seattle, Washington 98122

Aneuploidy, a state in which the chromosome number deviates from a multiple of the haploid count, significantly impacts human health. The phenotypic consequences of aneuploidy are believed to arise from gene expression changes associated with the altered copy number of genes on the aneuploid chromosomes. To dissect the mechanisms underlying altered gene expression in aneuploids, we used RNA-seq to measure transcript abundance in colonies of the haploid Saccharomyces cerevisiae strain F45 and two aneuploid derivatives harboring disomies of chromosomes XV and XVI. F45 colonies display complex "fluffy" morphologies, while the disomic colonies are smooth, resembling laboratory strains. Our two disomes displayed similar transcriptional profiles, a phenomenon not driven by their shared smooth colony morphology nor simply by their karyotype. Surprisingly, the environmental stress response (ESR) was induced in F45, relative to the two disomes. We also identified genes whose expression reflected a nonlinear interaction between the copy number of a transcriptional regulatory gene on chromosome XVI, DIG1, and the copy number of other chromosome XVI genes. DIG1 and the remaining chromosome XVI genes also demonstrated distinct contributions to the effect of the chromosome XVI disome on ESR gene expression. Expression changes in aneuploids appear to reflect a mixture of effects shared between different aneuploidies and effects unique to perturbing the copy number of particular chromosomes, including nonlinear copy number interactions between genes. The balance between these two phenomena is likely to be genotype- and environment-specific.
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http://dx.doi.org/10.1534/g3.116.036160DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5217112PMC
January 2017

Quantitative analysis of colony morphology in yeast.

Biotechniques 2014 Jan;56(1):18-27

Pacific Northwest Diabetes Research Institute, Seattle, WA; Molecular and Cellular Biology Program, University of Washington, Seattle, WA.

Microorganisms often form multicellular structures such as biofilms and structured colonies that can influence the organism's virulence, drug resistance, and adherence to medical devices. Phenotypic classification of these structures has traditionally relied on qualitative scoring systems that limit detailed phenotypic comparisons between strains. Automated imaging and quantitative analysis have the potential to improve the speed and accuracy of experiments designed to study the genetic and molecular networks underlying different morphological traits. For this reason, we have developed a platform that uses automated image analysis and pattern recognition to quantify phenotypic signatures of yeast colonies. Our strategy enables quantitative analysis of individual colonies, measured at a single time point or over a series of time-lapse images, as well as the classification of distinct colony shapes based on image-derived features. Phenotypic changes in colony morphology can be expressed as changes in feature space trajectories over time, thereby enabling the visualization and quantitative analysis of morphological development. To facilitate data exploration, results are plotted dynamically through an interactive Yeast Image Analysis web application (YIMAA; http://yimaa.cs.tut.fi) that integrates the raw and processed images across all time points, allowing exploration of the image-based features and principal components associated with morphological development.
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http://dx.doi.org/10.2144/000114123DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3996921PMC
January 2014

Aneuploidy underlies a multicellular phenotypic switch.

Proc Natl Acad Sci U S A 2013 Jul 28;110(30):12367-72. Epub 2013 Jun 28.

Institute for Systems Biology, Seattle, WA 98109, USA.

Although microorganisms are traditionally used to investigate unicellular processes, the yeast Saccharomyces cerevisiae has the ability to form colonies with highly complex, multicellular structures. Colonies with the "fluffy" morphology have properties reminiscent of bacterial biofilms and are easily distinguished from the "smooth" colonies typically formed by laboratory strains. We have identified strains that are able to reversibly toggle between the fluffy and smooth colony-forming states. Using a combination of flow cytometry and high-throughput restriction-site associated DNA tag sequencing, we show that this switch is correlated with a change in chromosomal copy number. Furthermore, the gain of a single chromosome is sufficient to switch a strain from the fluffy to the smooth state, and its subsequent loss to revert the strain back to the fluffy state. Because copy number imbalance of six of the 16 S. cerevisiae chromosomes and even a single gene can modulate the switch, our results support the hypothesis that the state switch is produced by dosage-sensitive genes, rather than a general response to altered DNA content. These findings add a complex, multicellular phenotype to the list of molecular and cellular traits known to be altered by aneuploidy and suggest that chromosome missegregation can provide a quick, heritable, and reversible mechanism by which organisms can toggle between phenotypes.
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http://dx.doi.org/10.1073/pnas.1301047110DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3725063PMC
July 2013

A new panel of NS1 antibodies for easy detection and titration of influenza A virus.

J Med Virol 2010 Mar;82(3):467-75

Collaborative Anti-Viral Research Group, Institute of Molecular and Cell Biology, Singapore, Singapore.

The non-structural protein NS1 of the influenza A virus is a good target for the development of diagnostic assays. In this study, three NS1 monoclonal antibodies (mAbs) were generated by using recombinant NS1 protein of H5N1 virus and found to bind both the native and denatured forms of NS1. Two of the mAbs, 6A4 and 2H6, bind NS1 of three different strains of influenza A virus, namely H1N1, H3N2, and H5N1. Epitope mapping revealed that residues 42-53 of H5N1 NS1 are essential for the interaction with both mAbs. Between the three strains, there is only one amino acid difference in this domain, which is consistent with the observed cross-reactivities. On the other hand, mAb 1G1 binds to residues 206-215 of H5N1 NS1 and does not bind NS1 of H1N1 or H3N2. Furthermore, all three mAbs detected NS1 proteins expressed in virus infected MDCK cells and indirect immunofluorescence staining with mAbs 6A4 and 2H6 provided an alternative method for viral titer determination. Quantifying the numbers of fluorescent foci units yielded viral titers for three different isolates of H5N1 virus that are highly comparable to that obtained by observing cytopathic effect induced by virus infection. Importantly, this alternative method yields results at 1 day post-infection while the conventional method using cytopathic effect yields results at 3 days post-infection. The results showed that this new panel of NS1 antibodies can detect NS1 protein expressed during viral infection and can be used for fast and easy titration of influenza A virus. J. Med. Virol. 82:467-475, 2010. (c) 2010 Wiley-Liss, Inc.
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http://dx.doi.org/10.1002/jmv.21709DOI Listing
March 2010