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Yi, L.

Publications and source records attributed to Yi, L..

5 recordsLinked to original sources

A direct comparison of genome alignment and transcriptome pseudoalignment

MotivationGenome alignment of reads is the first step of most genome analysis workflows. In the case of RNA-Seq, transcriptome pseudoalignment of reads is a fast alternative to genome alignment, but the different \"coordinate systems\" of the genome and transcriptome have made it difficult to perform direct comparisons between the approaches.\n\nResultsWe have developed tools for converting genome alignments to transcriptome pseudoalignments, and conversely, for projecting transcriptome pseudoalignments to genome alignments. Using these tools, we performed a direct comparison of genome alignment with transcriptome pseudoalignment. We find that both approaches produce similar quantifications. This means that for many applications genome alignment and transcriptome pseudoalignment are interchangeable.\n\nAvailability and Implementationbam2tcc is a C++14 software for converting alignments in SAM/BAM format to transcript compatibility counts (TCCs) and is available at https://github.com/pachterlab/bam2tcc. kallisto genomebam is a user option of kallisto that outputs a sorted BAM file in genome coordinates as part of transcriptome pseudoalignment. The feature has been released with kallisto v0.44.0, and is available at https://pachterlab.github.io/kallisto/.\n\nSupplementary MaterialN/A\n\nContactLior Pachter (lpachter@caltech.edu)

bioinformatics

Identification of transcriptional signatures for cell types from single-cell RNA-Seq

Single-cell RNA-Seq makes it possible to characterize the transcriptomes of cell types and identify their transcriptional signatures via differential analysis. We present a fast and accurate method for discriminating cell types that takes advantage of the large numbers of cells that are assayed. When applied to transcript compatibility counts obtained via pseudoalignment, our approach provides a quantification-free analysis of 3 single-cell RNA-Seq that can identify previously undetectable marker genes.

bioinformatics

Gene-level differential analysis at transcript-level resolution

Gene-level differential expression analysis based on RNA-Seq is more robust, powerful and biologically actionable than transcript-level differential analysis. However aggregation of transcript counts prior to analysis results can mask transcript-level dynamics. We demonstrate that aggregating the results of transcript-level analysis allow for gene-level analysis with transcript-level resolution. We also show that p-value aggregation methods, typically used for meta-analyses, greatly increase the sensitivity of gene-level differential analyses. Furthermore, such aggregation can be applied directly to transcript compatibility counts obtained during pseudoalignment, thereby allowing for rapid and accurate model-free differential testing. The methods are general, allowing for testing not only of genes but also of any groups of transcripts, and we showcase an example where we apply them to perturbation analysis of gene ontologies.

bioinformatics

Molecular evolution, diversity and adaptation of H7N9 influenza A viruses in China

A novel H7N9 avian influenza virus has caused five human epidemics in China since 2013. The substantial increase in prevalence and the emergence of antigenically divergent or highly pathogenic (HP) H7N9 strains during the current outbreak raises concerns about the epizootic-potential of these viruses. Here, we investigate the evolution and adaptation of H7N9 by combining publicly available data with newly generated virus sequences isolated in Guangdong between 2015-2017. Phylogenetic analyses show that currently-circulating H7N9 viruses belong to distinct lineages with differing spatial distributions. Using ancestral sequence reconstruction and structural modelling we have identified parallel amino-acid changes on multiple separate lineages. Furthermore, we infer mutations in HA primarily occur at sites involved in receptor-recognition and/or antigenicity. We also identify seven new HP strains, which likely emerged from viruses circulating in eastern Guangdong around March 2016 and is further associated with a high rate of adaptive molecular evolution.

evolutionary biology

H+- and Na+- elicited swift changes of the microtubule system in the biflagellated green alga Chlamydomonas

The microtubule cytoskeletal system is integral to diverse cellular processes. Although microtubules are known for dynamic instability, the system is tightly controlled in typical interphase animal cells. In contrast, diverse evidence suggests that the system is mercurial in the unicellular fresh water green alga, Chlamydomonas, but intense autofluorescence from photosynthesis pigments has hindered the investigation. By expressing a bright fluorescent reporter protein at the endogenous level, we demonstrate in real time discreet sweeping changes in algal microtubules elicited by fluctuation of intracellular H+ and Na+. These results suggest disparate sensitivity of this vital yet delicate system in diverse organisms; and illuminate how pH may drive crucial cellular processes; how plants respond to, and perhaps sense stresses; and how many species could be susceptible to accelerated changes in global environments.

cell biology