TROM: A Testing-based Method for Finding Transcriptomic Similarity of Biological Samples

Comparative transcriptomics has gained increasing popularity in genomic research thanks to the development of high-throughput technologies including microarray and next-generation RNA sequencing that have generated numerous transcriptomic data. An important question is to understand the conservation and differentiation of biological processes in different species. We propose a testing-based method TROM (Transcriptome Overlap Measure) for comparing transcriptomes within or between different species, and provide a different perspective to interpret transcriptomic similarity in contrast to traditional correlation analyses. Specifically, the TROM method focuses on identifying associated genes that capture molecular characteristics of biological samples, and subsequently comparing the biological samples by testing the overlap of their associated genes. We use simulation and real data studies to demonstrate that TROM is more powerful in identifying similar transcriptomes and more robust to stochastic gene expression noise than Pearson and Spearman correlations. We apply TROM to compare the developmental stages of six Drosophila species, C. elegans, S. purpuratus, D. rerio and mouse liver, and find interesting correspondence patterns that imply conserved gene expression programs in the development of these species. The TROM method is available as an R package on CRAN (http://cran.r-project.org/) with manuals and source codes available at http://www.stat.ucla.edu/ jingyi.li/software-and-data/trom.html

The Dust Tail of Asteroid (3200) Phaethon

We report the discovery of a comet-like tail on asteroid (3200) Phaethon when imaged at optical wavelengths near perihelion. In both 2009 and 2012, the tail appears >=350" (2.5x10^8 m) in length and extends approximately in the projected anti-solar direction. We interpret the tail as being caused by dust particles accelerated by solar radiation pressure. The sudden appearance and the morphology of the tail indicate that the dust particles are small, with an effective radius ~1 micrometer and a combined mass ~3x10^5 kg. These particles are likely products of thermal fracture and/or desiccation cracking under the very high surface temperatures (~1000 K) experienced by Phaethon at perihelion. The existence of the tail confirms earlier inferences about activity in this body based on the detection of anomalous brightening. Phaethon, the presumed source of the Geminid meteoroids, is still active.Comment: 13 pages, 4 figures. Accepted by ApJ

MSIQ: Joint Modeling of Multiple RNA-seq Samples for Accurate Isoform Quantification

Next-generation RNA sequencing (RNA-seq) technology has been widely used to assess full-length RNA isoform abundance in a high-throughput manner. RNA-seq data offer insight into gene expression levels and transcriptome structures, enabling us to better understand the regulation of gene expression and fundamental biological processes. Accurate isoform quantification from RNA-seq data is challenging due to the information loss in sequencing experiments. A recent accumulation of multiple RNA-seq data sets from the same tissue or cell type provides new opportunities to improve the accuracy of isoform quantification. However, existing statistical or computational methods for multiple RNA-seq samples either pool the samples into one sample or assign equal weights to the samples when estimating isoform abundance. These methods ignore the possible heterogeneity in the quality of different samples and could result in biased and unrobust estimates. In this article, we develop a method, which we call "joint modeling of multiple RNA-seq samples for accurate isoform quantification" (MSIQ), for more accurate and robust isoform quantification by integrating multiple RNA-seq samples under a Bayesian framework. Our method aims to (1) identify a consistent group of samples with homogeneous quality and (2) improve isoform quantification accuracy by jointly modeling multiple RNA-seq samples by allowing for higher weights on the consistent group. We show that MSIQ provides a consistent estimator of isoform abundance, and we demonstrate the accuracy and effectiveness of MSIQ compared with alternative methods through simulation studies on D. melanogaster genes. We justify MSIQ's advantages over existing approaches via application studies on real RNA-seq data from human embryonic stem cells, brain tissues, and the HepG2 immortalized cell line

A Bootstrap Lasso + Partial Ridge Method to Construct Confidence Intervals for Parameters in High-dimensional Sparse Linear Models

Constructing confidence intervals for the coefficients of high-dimensional sparse linear models remains a challenge, mainly because of the complicated limiting distributions of the widely used estimators, such as the lasso. Several methods have been developed for constructing such intervals. Bootstrap lasso+ols is notable for its technical simplicity, good interpretability, and performance that is comparable with that of other more complicated methods. However, bootstrap lasso+ols depends on the beta-min assumption, a theoretic criterion that is often violated in practice. Thus, we introduce a new method, called bootstrap lasso+partial ridge, to relax this assumption. Lasso+partial ridge is a two-stage estimator. First, the lasso is used to select features. Then, the partial ridge is used to refit the coefficients. Simulation results show that bootstrap lasso+partial ridge outperforms bootstrap lasso+ols when there exist small, but nonzero coefficients, a common situation that violates the beta-min assumption. For such coefficients, the confidence intervals constructed using bootstrap lasso+partial ridge have, on average, $50\%$ larger coverage probabilities than those of bootstrap lasso+ols. Bootstrap lasso+partial ridge also has, on average, $35\%$ shorter confidence interval lengths than those of the de-sparsified lasso methods, regardless of whether the linear models are misspecified. Additionally, we provide theoretical guarantees for bootstrap lasso+partial ridge under appropriate conditions, and implement it in the R package "HDCI.

EpiAlign: an alignment-based bioinformatic tool for comparing chromatin state sequences.

The availability of genome-wide epigenomic datasets enables in-depth studies of epigenetic modifications and their relationships with chromatin structures and gene expression. Various alignment tools have been developed to align nucleotide or protein sequences in order to identify structurally similar regions. However, there are currently no alignment methods specifically designed for comparing multi-track epigenomic signals and detecting common patterns that may explain functional or evolutionary similarities. We propose a new local alignment algorithm, EpiAlign, designed to compare chromatin state sequences learned from multi-track epigenomic signals and to identify locally aligned chromatin regions. EpiAlign is a dynamic programming algorithm that novelly incorporates varying lengths and frequencies of chromatin states. We demonstrate the efficacy of EpiAlign through extensive simulations and studies on the real data from the NIH Roadmap Epigenomics project. EpiAlign is able to extract recurrent chromatin state patterns along a single epigenome, and many of these patterns carry cell-type-specific characteristics. EpiAlign can also detect common chromatin state patterns across multiple epigenomes, and it will serve as a useful tool to group and distinguish epigenomic samples based on genome-wide or local chromatin state patterns

Quantification of three-dimensional folding using fluvial terraces: A case study from the Mushi anticline, northern margin of the Chinese Pamir

Fold deformation in three dimensions involves shortening, uplift, and lateral growth. Fluvial terraces represent strain markers that have been widely applied to constrain a fold's shortening and uplift. For the lateral growth, however, the utility of fluvial terraces has been commonly ignored. Situated along northern margin of Chinese Pamir, the Mushi anticline preserves, along its northern flank, flights of passively deformed fluvial terraces that can be used to constrain three-dimensional folding history, especially lateral growth. The Mushi anticline is a geometrically simple fault-tip fold with a total shortening of 740?±?110?m and rock uplift of ~1300?m. Geologic and geomorphic mapping and dGPS surveys reveal that terrace surfaces perpendicular to the fold's strike display increased rotation with age, implying the fold grows by progressive limb rotation. We use a pure-shear fault-tip fold model to estimate a uniform shortening rate of 1.5?+?1.3/?0.5?mm/a and a rock-uplift rate of 2.3?+?2.1/?0.8?mm/a. Parallel to the fold's strike, longitudinal profiles of terrace surfaces also display age-dependent increases in slopes. We present a new model to distinguish lateral growth mechanisms (lateral lengthening and/or rotation above a fixed tip). This model indicates that eastward lengthening of the Mushi anticline ceased by at least ~134?ka and its lateral growth has been dominated by rotation. Our study confirms that terrace deformation along a fold's strike not only can constrain the lateral lengthening rate but can serve to quantify the magnitude and rate of lateral rotation: attributes that are commonly difficult to define when relying on other geomorphic criteria

Disintegrating Asteroid P/2013 R3

Splitting of the nuclei of comets into multiple components has been frequently observed but, to date, no main-belt asteroid has been observed to break-up. Using the Hubble Space Telescope, we find that main-belt asteroid P/2013 R3 consists of 10 or more distinct components, the largest up to 200 m in radius (assumed geometric albedo of 0.05) each of which produces a coma and comet-like dust tail. A diffuse debris cloud with total mass roughly 2x10^8 kg further envelopes the entire system. The velocity dispersion among the components is about V = 0.2 to 0.5 m/s, is comparable to the gravitational escape speeds of the largest members, while their extrapolated plane-of-sky motions suggest break-up between February and September 2013. The broadband optical colors are those of a C-type asteroid. We find no spectral evidence for gaseous emission, placing model-dependent upper limits to the water production rate near 1 kg/s. Breakup may be due to a rotationally induced structural failure of the precursor body.Comment: 16 pages, 3 figures; accepted by ApJ