Biology subjects

Liu, Z.

Publications and source records attributed to Liu, Z..

At least 1,225 records · Page 68Linked to original sources

bioRxiv2017

Diabetes and dementia incidence in Latin America; a 10/66 population-based cohort study

BackgroundDiabetes prevalence is already high in middle income countries, particularly among older people. Current evidence on diabetes as a risk factor for dementia is limited to cohort studies in high income countries. Few studies carried out fasting glucose assessments to identify undiagnosed cases, and assess diabetes control. We aimed to determine the association between both diagnosed diabetes and total diabetes (including undiagnosed cases) and incident dementia, examining also the impact of glycaemic control on dementia risk.\n\nMethodsPopulation-based cohort studies of those aged 65 years and over in sites in Cuba, Dominican Republic, Puerto Rico, Peru, Venezuela, and Mexico. Diagnosed diabetes was assessed through self-reported diagnosis, and undiagnosed diabetes through fasting blood samples (glucose >= 7mmol/L). Blood pressure, smoking, underactivity and waist circumference were assessed from questionnaires and physical examination. Incident 10/66 dementia (and subtypes), and mortality, were ascertained three to five years later.\n\nResults12,297 interviews were completed at baseline, with 80-95% responding by site. The at risk cohort comprised 10,945 dementia-free individuals, of whom 8,171 (75%) provided blood samples. Mean age varied from 72.0 to 75.1 years by site. Total diabetes prevalence was 43.5% in Puerto Rico, ranging from 11.5% to 27.0% in other sites. Most diabetes cases (50.2% to 68.4%) were not controlled (fasting glucose >7.0 mmol/L). 7,000 participants were followed up for 26,423 person-years with 659 incident dementia cases, and 905 dementia free deaths. Total diabetes was associated with incident 10/66 dementia (pooled meta-analysed adjusted sub-hazard ratio [pASHR] 1.25, 95% CI, 1.05-1.49, I2=48.6%), with a stronger association for uncontrolled (pASHR 1.47, 95% CI 1.19-1.81, I2=49.6%) than controlled cases (pASHR 1.29, 95% CI 0.95-1.74, I2=13.3%). Total diabetes was strongly associated with the incidence of vascular dementia (pASHR 2.25, 95% CI 1.24-4.08, I2=23.7%), but not Alzheimers Disease (pASHR 0.99, 95% CI 0.70-1.42, I2=49.0%).\n\nConclusionsDiabetes, particularly when poorly controlled, may increase dementia risk. There is considerable scope for improved detection and control of diabetes among older people in these settings, and hence an opportunity to carry out proof of concept prevention trials. Overlapping epidemics of these age dependent disorders will challenge poorly-resourced health systems in the future.

epidemiology↗

bioRxiv2017

Whole exome sequencing study of colorectal cancer in Chinese population reveals novel prevalently mutated genes and decreased mutation frequency of APC and Wnt signaling in lymph node positive cancer

Colorectal cancer is the fifth prevalent cancer in China. Nevertheless, a large-scale characterization of Chinese colorectal cancer mutation spectrum has not been carried out. In this study, we have performed whole exome-sequencing analysis of 98 patients tumor samples with matched pairs of normal colon tissues using Illumina and Complete Genomics high-throughput sequencing platforms. Canonical CRC somatic gene mutations with high prevalence (>10%) have been verified, including TP53, APC, KRAS, SMAD4, FBXW7 and PIK3CA. PEG3 is identified as a novel frequently mutated gene (10.6%). APC and Wnt signaling exhibit significantly lower mutation frequencies than those in TCGA data. Analysis with clinical characteristics indicates that APC gene and Wnt signaling display lower mutation rate in lymph node positive cancer than negative ones, which are not observed in TCGA data. APC gene and Wnt signaling are considered as the key molecule and pathway for colorectal cancer initiation, and these findings greatly undermine their importance in tumor progression for Chinese patients. Taken together, the application of next-generation sequencing has led to the determination of novel somatic mutations and alternative disease mechanisms in colorectal cancer progression, which may be useful for understanding disease mechanism and personalizing treatment for Chinese patients.

genomics↗

bioRxiv2017

Neural mechanisms driving hunger-induced changes in sensory perception and behavior in Caenorhabditis elegans

Animals integrate changes in external and internal environments to generate behavior. While neural circuits detecting external cues have been mapped, less is known about how internal states like hunger are integrated into behavioral outputs. We use the nematode C. elegans to decode how changes in internal nutritional status affects chemosensory behaviors. We show that acute food deprivation leads to a reversible decline in repellent, but not attractant, sensitivity. This behavioral change requires two conserved transcription factors MML-1 (Mondo A) and HLH-30 (TFEB), both of which translocate from the intestinal nuclei to the cytoplasm upon food deprivation. Next, we identify insulin-like peptides INS-23 and INS-31 as candidate ligands relaying food-status signals from the intestine to other tissues. Furthermore, we show that ASI chemosensory neurons use the DAF-2 insulin receptor, PI-3 Kinase, and the mTOR complex to integrate these intestine-released peptides. Together, our study shows how internal food status signals are integrated by transcription factors and intestine-neuron signaling to generate flexible behaviors. Author SummaryWe have all experienced behavioral changes when we are hungry - the pang in our stomach can cause us to behave erratically. In particular, hungry animals, including humans, are known to pursue behaviors that involve higher risk compared to when they are well-fed. Here we explore the molecular details of this behavior in the invertebrate animal model C. elegans. This behavior, termed sensory integration, shows that C. elegans display reduced copper sensitivity when hungry. Copper is toxic and repellant to C. elegans; reduced avoidance indicates that these animals use riskier food search behaviors when they are hungry. Luckily, like us, this behavioral change is reversible upon re-feeding. This hunger-induced behavioral change is not due to increased attraction to food or depletion of fat stores, but rather insulin signaling between the intestine and specific neurons. We use genetic tools, microscopy, and behavioral tests to determine that this risky behavior involves sensation of "lack of food" in the intestine, release of signaling molecules, and engagement with sensory neurons. Our work highlights new and potentially evolutionarily conserved ways in which intestinal cells and neurons communicate leading to largescale behavioral change, providing further support for the importance of the gut-brain-axis.

neuroscience↗

bioRxiv2017

Deep Residual Network Reveals a Nested Hierarchy of Distributed Cortical Representation for Visual Categorization

The brain represents visual objects with topographic cortical patterns. To address how distributed visual representations enable object categorization, we established predictive encoding models based on a deep residual neural network, and trained them to predict cortical responses to natural movies. Using this predictive model, we mapped human cortical representations to 64,000 visual objects from 80 categories with high throughput and accuracy. Such representations covered both the ventral and dorsal pathways, reflected multiple levels of object features, and preserved semantic relationships between categories. In the entire visual cortex, object representations were modularly organized into three categories: biological objects, non-biological objects, and background scenes. In a finer scale specific to each module, object representations revealed sub-modules for further categorization. These findings suggest that increasingly more specific category is represented by cortical patterns in progressively finer spatial scales. Such a nested hierarchy may be a fundamental principle for the brain to categorize visual objects with various levels of specificity, and can be explained and differentiated by object features at different levels.

neuroscience↗

bioRxiv2017

Predator-secreted sulfolipids induce fear-like defense responses in C. elegans

Animals respond to predators by altering their behavior and physiological states, but the underlying signaling mechanisms are poorly understood. Using the interactions between Caenorhabditis elegans and its predator, Pristionchus pacificus, we show that neuronal perception by C. elegans of a predator-specific molecular signature induces instantaneous escape behavior and a prolonged reduction in oviposition. Chemical analysis revealed this predator-specific signature to consist of a class of sulfolipids, produced by a biochemical pathway required for developing predacious behavior and specifically induced by starvation. These sulfolipids are detected by four pairs of C. elegans amphid sensory neurons that act redundantly and recruit cyclic nucleotide-gated (CNG) or transient receptor potential (TRP) channels to drive both escape and reduced oviposition. Specific abolishment of predator-evoked C. elegans responses by the anti-anxiety drug sertraline as well as functional homology of the delineated signaling pathways suggests a conserved or convergent strategy for managing predator threats.

neuroscience↗

bioRxiv2017

A group of nuclear factor Y transcription factors are likely sub-functionalized in the endosperm development of rice and other monocots

Nuclear factor Y (NF-Y) is a heterotrimeric transcription factor that consists of three subunits, NF-YA, NF-YB, and NF-YC. Although NF-Ys play multiple roles in plant development, their functions during endosperm development are not well understood. In this study, we identified eight NF-Y encoding genes, including OsNF-YA8, OsNF-YB1,9, and OsNF-YC8,9,10,11,12, which predominantly express in the rice endosperm. Interestingly, the closest homologs of these OsNF-Ys are present only in the monocot species. All the genes are preferentially expressed in the endosperm, suggesting their roles in the regulation of endosperm development. A systemic analysis of the interactions between rice endosperm-preferential NF-Ys in yeast revealed that NF-YBs and NF-YCs could interact with each other. OsNF-YA8 is a recently evolved NF-YA in rice. Generally, NF-YA does not interact with NF-YB monomers in plants; however, in the present study, we found that OsNY-YA8 interacts with OsNF-YB9. Our results also indicated that the endosperm-preferential OsNF-YBs and OsNF-YCs could interact with some ethylene response factors (ERFs) of rice. Unlike the OsNF-YC8,9,10, the members of OsNF-YB1, 9 or OsNF-YC 11 and 12 showed lack of transcriptional activation when present alone. However, they displayed functional activity while in dimer form. In addition, OsNF-YB1 knockout lines showed significant changes in the seed morphology, further confirms its role in endosperm development. Our findings have provided strong evidences that the group of phylogenetically conserved NF-Ys are differentiated in monocots to regulate the endosperm development.

plant biology↗

bioRxiv2017

Coupling effect of morphology and mechanical properties contributes to the tribological behaviors of snake scales

It is known that the tribological behaviors of snake skins are contributed by the synergistic action of multiple factors, such as surface morphology and mechanical properties, which has inspired fabrication of scale-like surface textures in recent years. However, the coupling effect and mechanism remain to be elucidated. In this work, the morphology and mechanical properties of the scales from different body sections (leading body half, middle trunk and trailing body half) and positions (dorsal, lateral and ventral) of Boa constrictor and Eryx tataricus have been characterized and compared to investigate the corresponding effects on the tribological behaviors and to probe the possible coupling mechanism. The morphological characterizations of scanning electron microscopy and atomic force microscopy have revealed significant differences between the two species with the roughness of scales from Boa constrictor being larger in general. The mechanical properties measured by nanoindentation have corroboratively demonstrated substantial differences in terms of elastic modulus and hardness. Meanwhile, tribological characterizations of scales in different body positions from the two species also exhibit evident anisotropy. Interestingly, the ventral scales manifest higher friction coefficients but lower surface roughness, together with relatively larger elastic modulus and hardness. A \"double-crossed\" hypothesis has been proposed to explain the observed coupling effect of the morphology and mechanical properties on friction, which may afford valuable insights for the design of materials with desirable tribological performance.

animal behavior and cognition↗

bioRxiv2017

Musical Imagery Involves the Wernicke’s Area in Bilateral and Anti-Correlated Network Interactions in Musicians

Musical imagery is a human experience of imagining music without actually hearing it. The neural basis of such a mental ability is unclear, especially for musicians capable of accurate and vivid musical imagery due to their musical training. Here, we visualized an 8-min symphony as a silent movie, and used it as real-time cues for musicians to continuously imagine the music for multiple synchronized sessions during functional magnetic resonance imaging. The activations and networks evoked by musical imagery were compared with those when the subjects directly listened to the same music. The musical imagery and perception shared similar responses at bilateral secondary auditory areas and Wernickes area for encoding the musical feature. But the Wernickes area was involved in highly distinct network interactions during musical imagery vs. perception. The former involved positive correlations with a subset of the auditory network and the attention network, but negative correlations with the default mode network; the latter was confined to the intrinsic auditory network in the resting state. Our results highlight the important role of the Wernickes area in forming vivid musical imagery through bilateral and anti-correlated network interactions, challenging the conventional view of segregated and lateralized processing of music vs. language.

neuroscience↗

bioRxiv2017

Characterization Of Imprinted Genes In Rice Reveals Post-Fertilization Regulation And Conservation At Some Loci Of Imprinting In Plant Species

Genomic imprinting is an epigenetic phenomenon by which certain genes display monoallelic expression in a parent-of-origin-dependent manner. Hundreds of imprinted genes have been identified from several plant species. Here we identified, with a high level of confidence, 208 imprinted candidates from rice. Imprinted genes of rice showed limited association to the transposable elements, which is contrast to the findings in Arabidopsis. Generally, imprinting of rice is conserved within species, but intraspecific variations were confirmed here. Imprinting between cultivated rice and wild rice are likely similar. The imprinted genes of rice do not show significant selective signatures overall, which suggests that domestication imposes limited evolutionary effects on genomic imprinting of rice. Though the conservation of imprinting in plants is limited, here we prove that some loci tend to be imprinted in different species. In addition, our results suggest that differential epigenetic regulation between parental alleles can be established either prior to or post-fertilization. The imprinted 24-nt small RNAs, but not the 21-nt ones, likely involve the regulation of imprinting in an opposite parental-allele targeting manner. Together, our findings suggest that regulation of imprinting can be very diverse, and genomic imprinting as well as imprinted genes have essential evolutionary and biological significance.

plant biology↗

bioRxiv2017

Leg Length, Skull Circumference, And The Incidence Of Dementia In Latin America And China; A 10/66 Population-Based Cohort Study

BackgroundAdult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. Cross-sectional studies indicate inverse associations with dementia risk, but there have been few prospective studies.\n\nMethodsPopulation-based cohort studies in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, and anthropometric measures taken, with ascertainment of incident 10/66 dementia, and mortality, three to five years later.\n\nResultsOf the original at risk cohort of 13,587 persons aged 65 years and over, 2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference assessments were followed up for 40,466 person years, and 10,400 with leg length assessments were followed up for 39,954 person years. There were 1,009 cases of incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta-analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest quarter) was 0.80 (95% CI, 0.66-0.97) and for skull circumference was 1.02 (95% CI, 0.84-1.25), with no heterogeneity of effect between sites (I2=0%). Leg length measurements tended to be shorter at follow-up, particularly for those with baseline cognitive impairment and dementia. However, leg length change was not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992-1.020), and the effect of leg length was little altered after adjusting for baseline frailty (ASHT 0.82, 95% CI 0.67-0.99). A priori hypotheses regarding effect modification by gender or educational level were not supported.\n\nConclusionsConsistent findings across settings provide quite strong support for an association between adult leg length and dementia incidence in late-life. Leg length is a relatively stable marker of early life nutritional programming, which may confer brain reserve and protect against neurodegeneration in later life through mitigation of cardiometabolic risk. Further clarification of these associations could inform predictive models for future dementia incidence in the context of secular trends in adult height, and invigorate global efforts to improve childhood nutrition, growth and development.

epidemiology↗

bioRxiv2017

Reproductive Period, Endogenous Estrogen Exposure And Dementia Incidence Among Women In Latin America And China; A 10/66 Population-Based Cohort Study

BackgroundExposure to endogenous estrogen may protect against dementia, but evidence remains equivocal. Such effects may be assessed more precisely in settings where exogenous estrogen administration is rare. We aimed to determine whether reproductive period (menarche to menopause), and other indicators of endogenous estrogen exposure are inversely associated with dementia incidence\n\nMethodsPopulation-based cohort studies, of women aged 65 years and over in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, including ages at menarche, birth of first child, and menopause, and parity, with ascertainment of incident 10/66 dementia, and mortality, three to five years later.\n\nResults9,428 women participated in the baseline phase, with response rates of 72-98% by site. The at risk cohort comprised 8,466 dementia-free women. Mean age at baseline varied from 72.0 to 75.4 years, lower in rural than urban sites and in China than in Latin America. Mean parity was 4.1, generally higher in rural than urban sites and ranging from 2.4-7.2 by site. 6,854 women with baseline reproductive period data were followed up for 26,463 person years. There were 692 cases of incident dementia, and 895 dementia free deaths. Pooled meta-analysed fixed effects, per year, for reproductive period (Adjusted Sub-Hazard Ratio [ASHR] 1.001, 95% CI 0.988-1.015) did not support any association with dementia incidence, with no evidence also for any interaction between APOE genotype and reproductive period (ASHR 0.993, 95% CI 0.947-1.041, I2=39.3%). Similarly no association was observed between incident dementia and; ages at menarche, birth of first child, and menopause: nulliparity; or index of cumulative endogenous estrogen exposure. Greater parity was positively associated with incident dementia (ASHR 1.030, 95% CI 1.002-1.059, I2=0.0%).\n\nConclusionsWe found no evidence to support the theory that natural variation in cumulative exposure to endogenous oestrogens across the reproductive period influences the incidence of dementia in late life.

epidemiology↗

bioRxiv2017

A Next Generation Connectivity Map: L1000 Platform And The First 1,000,000 Profiles

We previously piloted the concept of a Connectivity Map (CMap), whereby genes, drugs and disease states are connected by virtue of common gene-expression signatures. Here, we report more than a 1,000-fold scale-up of the CMap as part of the NIH LINCS Consortium, made possible by a new, low-cost, high throughput reduced representation expression profiling method that we term L1000. We show that L1000 is highly reproducible, comparable to RNA sequencing, and suitable for computational inference of the expression levels of 81% of non-measured transcripts. We further show that the expanded CMap can be used to discover mechanism of action of small molecules, functionally annotate genetic variants of disease genes, and inform clinical trials. The 1.3 million L1000 profiles described here, as well as tools for their analysis, are available at https://clue.io.\n\nHIGHLIGHTSO_LIA new gene expression profiling method, L1000, dramatically lowers cost\nC_LIO_LIThe Connectivity Map database now includes 1.3 million publicly accessible L1000 perturbational profiles\nC_LIO_LIThis expanded Connectivity Map facilitates discovery of small molecule mechanism of action and functional annotation of genetic variants\nC_LIO_LIThe work establishes feasibility and utility of a truly comprehensive Connectivity Map\nC_LI

genomics↗

bioRxiv2017

Molecular Mapping Of YrTZ2, A Stripe Rust Resistance Gene In Wild Emmer Accession TZ-2 And Its Comparative Analyses With Aegilops tauschii

Wheat stripe rust, caused by Puccinia striiformis f. sp. tritici (Pst), is a devastating disease that can cause severe yield losses. Identification and utilization of stripe rust resistance genes are essential for effective breeding against the disease. Wild emmer accession TZ-2, originally collected from Mount Hermon, Israel, confers near-immunity resistance against several prevailing Pst races in China. A set of 200 F6:7 recombinant inbred lines (RILs) derived from a cross between susceptible durum wheat cultivar Langdon and TZ-2 was used for stripe rust evaluation. Genetic analysis indicated that the stripe rust resistance of TZ-2 to Pst race CYR34 was controlled by a single dominant gene, temporarily designated YrTZ2. Through bulked segregant analysis (BSA) and SSR mapping, YrTZ2 was located on chromosome arm 1BS and flanked by SSR markers Xwmc230 and Xgwm413 with genetic distance of 0.8 cM (distal) and 0.3 cM (proximal), respectively. By applying wheat 90K iSelect SNP genotyping assay, 11 polymorphic loci (consist of 250 SNP markers) closely linked with YrTZ2 were identified. YrTZ2 was further delimited into a 0.8 cM genetic interval between SNP marker IWB19368 and SSR marker Xgwm413, and co-segregated with SNP marker IWB28744 (attached with 28 SNP markers). Comparative genomics analyses revealed high level of collinearity between the YrTZ2 genomic region and the orthologous region of Aegilops tauschii 1DS. The genomic region between loci IWB19368 and IWB31649 harboring YrTZ2 is orthologous to a 24.5 Mb genomic region between AT1D0112 and AT1D0150, spanning 15 contigs on chromosome 1DS. The genetic and comparative maps of YrTZ2 provide framework for map-based cloning and marker-assisted selection (MAS) of YrTZ2.

plant biology↗

bioRxiv2017

Stem cell intrinsic, Seven-up-triggered temporal factor gradients diversify intermediate neural progenitors

Drosophila type II neuroblasts produce numerous neurons and glia due to transiently amplifying, intermediate neural progenitors (INP). Consecutively born INPs produce morphologically distinct progeny, presumably due to temporal patterning in type II neuroblasts. We therefore profiled type II neuroblasts transcriptome across time. Our results reveal opposing temporal gradients of Imp and Syp RNA-binding proteins (descending and ascending, respectively). Maintaining Imp expression throughout brain development expands the number of neurons/glia with early temporal fate at the expense of cells with late fate. Conversely, precocious upregulation of Syp reduces the number of cells with early fate. Further, we reveal that the transcription factor, Seven-up initiates progression of the Imp/Syp gradients. Interestingly, genetic manipulations that fix Imp or Syp levels still yield progeny with a small range of early fates. We propose that the Seven-up-initiated Imp/Syp gradients create coarse temporal windows within type II neuroblasts to pattern INPs, which subsequently undergo fine-tuned subtemporal patterning.

neuroscience↗

bioRxiv2017

Dynamic response to initial stage blindness in visual system development

Sensitive periods and experience-dependent plasticity have become core issues in visual system development. Converging evidence indicates that visual experience is an indispensable factor in establishing mature visual system circuitry during sensitive periods and the visual system exhibits substantial plasticity when facing deprivation. The mechanisms that underlie the environmental regulation of visual system development and plasticity are of great interest but need further exploration. Here, we investigated a unique sample of human infants who experienced initial stage blindness (beginning at birth and lasting 2 to 8 months) before the removal of bilateral cataracts. Retinal thickness, axial length, refractive status, visual grating acuity and genetic integrity were recorded during the preoperative period or at surgery, and then during follow-up. The results showed that the development of the retina is malleable and associated with external environment influences. Our work supported that the retina might play critical roles in the development of the experience-dependent visual system and its malleability might partly contribute to the sensitive period plasticity.\n\nSUMMARY STATEMENTThe follow-up investigation of a group of human infants, who experienced initial stage blindness before the removal of bilateral cataracts, revealed that retinal development is associated with environment influences and its malleability might be a potential basis of plasticity.

developmental biology↗

bioRxiv2017

Stochastic Protein Labeling Enables Long-term Single Molecule Observation In Vivo

Our ability to unambiguously image and track individual molecules in live cells is limited by packing of multiple copies of labeled molecules within the resolution limit. Here we devise a universal genetic strategy to precisely control copy number of fluorescently labeled molecules in a cell. This system has a dynamic titration range of >10,000 fold, enabling sparse labeling of proteins expressed at different abundance levels. Combined with photostable labels, this system extends the duration of automated single-molecule tracking by 2 orders of magnitude. We demonstrate long-term imaging of synaptic vesicle dynamics in cultured neurons as well as in intact zebrafish. We found axon initial segment utilizes a waterfall mechanism gating synaptic vesicle transport polarity by promoting anterograde transport processivity. Long-time observation also reveals that transcription factor hops between clustered binding sites in spatially-restricted sub-nuclear regions, suggesting that topological structures in the nucleus shape local gene activities by a sequestering mechanism. This strategy thus greatly expands the spatiotemporal length scales of live-cell single-molecule measurements, enabling new experiments to quantitatively understand complex control of molecular dynamics in vivo.

biophysics↗

bioRxiv2017

A powerful approach to estimating annotation-stratified genetic covariance using GWAS summary statistics

Despite the success of large-scale genome-wide association studies (GWASs) on complex traits, our understanding of their genetic architecture is far from complete. Jointly modeling multiple traits genetic profiles has provided insights into the shared genetic basis of many complex traits. However, large-scale inference sets a high bar for both statistical power and biological interpretability. Here we introduce a principled framework to estimate annotation-stratified genetic covariance between traits using GWAS summary statistics. Through theoretical and numerical analyses we demonstrate that our method provides accurate covariance estimates, thus enabling researchers to dissect both the shared and distinct genetic architecture across traits to better understand their etiologies. Among 50 complex traits with publicly accessible GWAS summary statistics (Ntotal {approx} 4.5 million), we identified more than 170 pairs with statistically significant genetic covariance. In particular, we found strong genetic covariance between late-onset Alzheimers disease (LOAD) and amyotrophic lateral sclerosis (ALS), two major neurodegenerative diseases, in single-nucleotide polymorphisms (SNPs) with high minor allele frequencies and in SNPs located in the predicted functional genome. Joint analysis of LOAD, ALS, and other traits highlights LOADs correlation with cognitive traits and hints at an autoimmune component for ALS.

genetics↗

bioRxiv2017

SAVE: A secure cloud-based pipeline for CRISPR pooled screen deconvolution

We present a user-friendly, cloud-based, data analysis pipeline for the deconvolution of pooled screening data. This tool, termed SAVE for Screening Analysis Visual Explorer, serves a dual purpose of extracting, clustering and analyzing raw next generation sequencing files derived from pooled screening experiments while at the same time presenting them in a user-friendly way on a secure web-based platform. Moreover, SAVE serves as a useful web-based analysis pipeline for reanalysis of pooled CRISPR screening datasets. Taken together, the framework described in this study is expected to accelerate development of web-based bioinformatics tool for handling all studies which include next generation sequencing data. SAVE is available at http://save.nrihub.org.

bioinformatics↗