Biology subjects

Xiao, Y.

Publications and source records attributed to Xiao, Y..

347 records · Page 20Linked to original sources

bioRxiv2017

Multiplex Confounding Factor Correction for Genomic Association Mapping with Squared Sparse Linear Mixed Model

Genome-wide Association Study has presented a promising way to understand the association between human genomes and complex traits. Many simple polymorphic loci have been shown to explain a significant fraction of phenotypic variability. However, challenges remain in the non-triviality of explaining complex traits associated with multifactorial genetic loci, especially considering the confounding factors caused by population structure, family structure, and cryptic relatedness. In this paper, we propose a Squared-LMM (LMM2) model, aiming to jointly correct population and genetic confounding factors. We offer two strategies of utilizing LMM2 for association mapping: 1) It serves as an extension of univariate LMM, which could effectively correct population structure, but consider each SNP in isolation. 2) It is integrated with the multivariate regression model to discover association relationship between complex traits and multifactorial genetic loci. We refer to this second model as sparse Squared-LMM (sLMM2). Further, we extend LMM2/sLMM2 by raising the power of our squared model to the LMMn/sLMMn model. We demonstrate the practical use of our model with synthetic phenotypic variants generated from genetic loci of Arabidopsis Thaliana. The experiment shows that our method achieves a more accurate and significant prediction on the association relationship between traits and loci. We also evaluate our models on collected phenotypes and genotypes with the number of candidate genes that the models could discover. The results suggest the potential and promising usage of our method in genome-wide association studies.

genomics↗

bioRxiv2017

Assembly and translocation of a CRISPR-Cas primed acquisition complex

Bacteria and archaea destroy foreign nucleic acids by mounting an RNA-based CRISPR-Cas adaptive immune response1-3. In type I CRISPR-Cas systems, the most frequently found type of CRISPR in bacteria and archaea3,4, foreign DNAs that trigger efficient immunity can also provoke primed acquisition of protospacers into the CRISPR locus5-12. Both interference and primed acquisition require Cascade (CRISPR-associated complex for antiviral defense) and the Cas3 helicase/nuclease. Primed acquisition also requires the Cas1-Cas2 integrase; however, the biophysical mechanisms of how interference and primed acquisition are coordinated have remained elusive. Here, we present single-molecule characterization of the type I-E Thermobifida fusca (Tfu) primed acquisition complex (PAC). TfuCascade rapidly samples non-specific DNA for its target via facilitated one-dimensional (1D) diffusion. An evolutionary-conserved positive patch on the Cse1 subunit increases the target recognition efficiency by promoting this 1D diffusion. Cas3 loads at target-bound Cascade and the Cascade/Cas3 complex initiates processive translocation via a looped DNA intermediate. Moving Cascade/Cas3 complexes stall and release the DNA loop at protein roadblocks. Cas1-Cas2 samples DNA transiently via 3D collisions, but stably associates with target-bound Cascade. Cas1-Cas2 also remains associated with translocating Cascade/Cas3, forming the PAC. By directly imaging all key subcomplexes involved in target recognition, interference, and primed acquisition, this work provides a molecular basis for the coordinated steps in CRISPR-based adaptive immunity.

biophysics↗

bioRxiv2017

Horizontal Gene Transfer Can Help Maintain the Equilibrium of Microbial Communities

Horizontal gene transfer and species coexistence are two focal points in the study of microbial communities. The evolutionary advantage of horizontal gene transfer has not been well-understood and is constantly being debated. Here we propose a simple population dynamics model based on the frequency-dependent interactions between different genotypes to evaluate the influence of horizontal gene transfer on microbial communities. We find that both structural stability and robustness of the microbial community are strongly affected by the gene transfer rate and direction. An optimal gene flux can stablize the ecosystem, helping it recover from disturbance and maintain the species coexistence.

evolutionary biology↗

bioRxiv2017

Mapping the ecological networks of microbial communities from steady-state data

Microbes form complex and dynamic ecosystems that play key roles in the health of the animals and plants with which they are associated. Such ecosystems are often represented by a directed, signed and weighted ecological network, where nodes represent microbial taxa and edges represent ecological interactions. Inferring the underlying ecological networks of microbial communities is a necessary step towards understanding their assembly rules and predicting their dynamical response to external stimuli. However, current methods for inferring such networks require assuming a particular population dynamics model, which is typically not known a priori. Moreover, those methods require fitting longitudinal abundance data, which is not readily available, and often does not contain the variation that is necessary for reliable inference. To overcome these limitations, here we develop a new method to map the ecological networks of microbial communities using steady-state data. Our method can qualitatively infer the inter-taxa interaction types or signs (positive, negative or neutral) without assuming any particular population dynamics model. Additionally, when the population dynamics is assumed to follow the classic Generalized Lotka-Volterra model, our method can quantitatively infer the inter-taxa interaction strengths and intrinsic growth rates. We systematically validate our method using simulated data, and then apply it to four experimental datasets of microbial communities. Our method offers a novel framework to infer microbial interactions and reconstruct ecological networks, and represents a key step towards reliable modeling of complex, real-world microbial communities, such as the human gut microbiota.

ecology↗

bioRxiv2017

Dehydration Bouts Prompt Increased Activity And Blood Feeding By Mosquitoes

Mosquitoes are prone to dehydration and respond to this stress through multiple mechanisms, but previous studies have examined very specific responses and fail to provide an encompassing view of the role that dehydration has on mosquito biology. This study examined underlying changes in biology of the northern house mosquito, Culex pipiens, associated with short bouts of dehydration. We show that dehydration increased blood feeding propensity of mosquitoes, which was the result of both enhanced activity and a higher tendency to land on a host. Mosquitoes exposed to dehydrating conditions with access to water or rehydrated individuals experience no water loss and failed to display behavioral changes. RNA-seq and metabolome analyses following dehydration indicated that factors associated with energy metabolism are altered, specifically the breakdown of trehalose to yield glucose, which likely underlies changes in mosquito activity. Suppression of trehalose breakdown by RNA interference reduced phenotypes associated with dehydration. Comparable results were noted for two other mosquito species, suggesting this is a general response among mosquitoes. Lastly, field-based mesocosm studies using C. pipiens revealed that dehydrated mosquitoes were more likely to host feed, and disease modeling indicates dehydration bouts may increase transmission of West Nile virus. These results suggest that periods of dehydration prompt mosquitoes to utilize blood feeding as a mechanism to obtain water. This dehydration-induced increase in blood feeding is likely to intensify disease transmission during periods of low water availability.\n\nSignificanceDehydration stress has substantial impacts on the biology of terrestrial invertebrates. To date, no studies have elucidated the difference between dehydration exposure and realized water loss in relation to mosquito behavior and physiology. Our experiments show that direct dehydration stress increases mosquito activity and subsequent blood feeding, likely as a mechanism to locate and utilize a bloodmeal for rehydration. These dehydration-induced phenotypes were linked to altered carbohydrate metabolism that acts as a source of energy. This study provides important insight into the impact of mosquito-dehydration dynamics on disease transmission that is likely general among mosquitoes.

physiology↗