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Ma, Q.

Publications and source records attributed to Ma, Q..

22 records · Page 2Linked to original sources

A probabilistic model-based bi-clustering method for single-cell transcriptomic data analysis

We present here novel computational techniques for tackling four problems related to analyses of single-cell RNA-Seq data: (1) a mixture model for coping with multiple cell types in a cell population; (2) a truncated model for handling the unquantifiable errors caused by large numbers of zeros or low-expression values; (3) a bi-clustering technique for detection of sub-populations of cells sharing common expression patterns among subsets of genes; and (4) detection of small cell sub-populations with distinct expression patterns. Through case studies, we demonstrated that these techniques can derive high-resolution information from single-cell data that are not feasible using existing techniques.

bioinformatics

Free-living human cells reconfigure their chromosomes in the evolution back to uni-cellularity

Cells of multi-cellular organisms evolve toward uni-cellularity in the form of cancer and, if humans intervene, continue to evolve in cell culture. During this process, gene dosage relationships may evolve in novel ways to cope with the new environment and may regress back to the ancestral unicellular state. In this context, the evolution of sex chromosomes vis-a-vis autosomes is of particular interest. Here, we report the chromosomal evolution in ~600 cancer cell lines. Many of them jettisoned either Y or the inactive X; thus, free-living male and female cells converge by becoming \"de-sexualized\". Surprisingly, the active X often doubled, accompanied by the addition of one haploid complement of autosomes, leading to an X:A ratio of 2:3 from the extant ratio of 1:2. Theoretical modeling of the frequency distribution of X:A karyotypes suggests that the 2:3 ratio confers a higher fitness and may reflect aspects of sex chromosome evolution.

genomics

ALUMINUM RESISTANCE TRANSCRIPTION FACTOR 1 (ART1) underlies a major Al resistance QTL and interacts with natural variation in the genetic background to quantitatively regulate Al resistance in rice.

Transcription factors (TFs) mediate stress resistance indirectly via physiological mechanisms driven by the genes they regulate. When studying TF-mediated stress resistance, it is important to understand how TFs interact with different genetic backgrounds. Here, we fine-mapped the aluminum (Al) resistance QTL Alt12.1 to a 44 Kb region containing six gene models. Among them is ART1, which encodes a C2H2-type zinc finger TF required for Al resistance in rice. The parents of the mapping population, Al-resistant Azucena (tropical japonica) and Al-sensitive IR64 (indica), showed similar ART1 expression levels but extensive sequence polymorphism within the ART1 coding region. Using reciprocal near-isogenic lines (NILs) in the Azucena and IR64 genetic backgrounds, we examined how allele-swapping Alt12.1 would affect plant responses to Al. Analysis of global transcriptional responses to Al stress in roots of the NILs alongside their recurrent parents demonstrated that the ART1 from Al-resistant Azucena led to greater changes in gene expression in response to Al when compared to the ART1 from IR64 in both genetic backgrounds. The presence of the ART1 allele from the opposite parent affected the expression of several genes not previously implicated in rice Al tolerance. We highlight examples where putatively functional variation in cis-regulatory regions of ART1-regulated genes interacts with ART1 to determine gene expression in response to Al. This ART1-promoter interaction may be associated with transgressive variation for Al resistance in the Azucena x IR64 population. These results illustrate how ART1 interacts with the genetic background to contribute to quantitative phenotypic variation in rice Al resistance.

plant biology

Worldwide Population Structure Of Escherichia coli Reveals Two Major Subspecies

Recombination is one of the most important mechanisms of prokaryotic species evolution but its exact roles are still in debate. Here we try to infer genome-wide recombination events within a species uti-lizing a dataset of 104 complete genomes of Escherichia coli from diverse origins, among which 45 from world-wide animal-hosts are in-house sequenced using SMRT (single-molecular real time) technology.Two major clades are identified based on evidences of ecological and physiological characteristics, as well as distinct genomic features implying scarce inter-clade genetic exchange. By comparing the synteny of identical fragments genome-widely searched for each genome pair, we achieve a fine-scale map of re-combination within the population. The recombination is rather extensive within clade, which is able to break linkages between genes but does not interrupt core genome framework and primary metabolic port-folios possibly due to natural selection for physiological compatibility and ecological fitness. Meanwhile,the recombination between clades declines drastically as the phylogenetic distance increases, generally 10-fold reduced than those of the intra-clade, which establishes genetic barrier between clades. These empirical data of recombination suggest its critical role in the early stage of speciation, where recombina-tion rate differs according to phylogentic distance. The extensive intra-clade recombination coheres sister strains into a quasi-sexual group and optimizes genes or alleles to streamline physiological activities,whereas shapely declined inter-clade recombination split the population into clades adaptive to divergent ecological niches.\n\nSignificance StatementRoles of recombination in species evolution have been debated for decades due to difficulties in inferring recombination events during the early stage of speciation, especially when recombination is always complicated by frequent gene transfer events of bacterial genomes. Based on 104 high-quality complete E. coli genomes, we infer gene-centric dynamics of recombination in the formation of two E. coli clades or subpopulations, and recombination is found to be rather intensive in a within-clade fashion, which forces them to be quasi-sexual. The recombination events can be mapped among individual genomes in the context of genes and their variations; decreased between-clade and increased intra-claderecombination engender a genetic barrier that further encourages clade-specific secondary metabolic portfolios for better environmental adaptation. Recombination is thus a major force that accelerates bacterial evolution to fit ecological diversity.

microbiology