Copy number variation (CNV) is a prevalent form of critical genetic variation that leads to an abnormal number of copies of large genomic regions in a cell. Microarray-based comparative genome hybridization (arrayCGH) or genotyping arrays have been standard technologies to detect large regions subject to copy number changes in genomes until most recently high-resolution sequence data can be analyzed by next-generation sequencing (NGS). During the last several years, NGS-based analysis has been widely applied to identify CNVs in both healthy and diseased individuals. Correspondingly, the strong demand for NGS-based CNV analyses has fuelled development of numerous computational methods and tools for CNV detection. In this article, we review the recent advances in computational methods pertaining to CNV detection using whole genome and whole exome sequencing data. Additionally, we discuss their strengths and weaknesses and suggest directions for future development.

Biomphalaria snails are instrumental in transmission of the human blood fluke Schistosoma mansoni. With the World Health Organization's goal to eliminate schistosomiasis as a global health problem by 2025, there is now renewed emphasis on snail control. Here, we characterize the genome of Biomphalaria glabrata, a lophotrochozoan protostome, and provide timely and important information on snail biology. We describe aspects of phero-perception, stress responses, immune function and regulation of gene expression that support the persistence of B. glabrata in the field and may define this species as a suitable snail host for S. mansoni. We identify several potential targets for developing novel control measures aimed at reducing snail-mediated transmission of schistosomiasis.

Tumor suppressor genes (TSGs) are a major type of gatekeeper genes in the cell growth. A knowledgebase with the systematic collection and curation of TSGs in multiple cancer types is critically important for further studying their biological functions as well as for developing therapeutic strategies. Since its development in 2012, the Tumor Suppressor Gene database (TSGene), has become a popular resource in the cancer research community. Here, we reported the TSGene version 2.0, which has substantial updates of contents (e.g. up-to-date literature and pan-cancer genomic data collection and curation), data types (noncoding RNAs and protein-coding genes) and content accessibility. Specifically, the current TSGene 2.0 contains 1217 human TSGs (1018 protein-coding and 199 non-coding genes) curated from over 9000 articles. Additionally, TSGene 2.0 provides thousands of expression and mutation patterns derived from pan-cancer data of The Cancer Genome Atlas. A new web interface is available at http://bioinfo.mc.vanderbilt.edu/TSGene/. Systematic analyses of 199 non-coding TSGs provide numerous cancer-specific non-coding mutational events for further screening and clinical use. Intriguingly, we identified 49 protein-coding TSGs that were consistently down-regulated in 11 cancer types. In summary, TSGene 2.0, which is the only available database for TSGs, provides the most updated TSGs and their features in pan-cancer.

Two nonradioactive methods for determining glomerular filtration rate (GFR) in conscious mice using FITC-labeled inulin (FITC-inulin) were evaluated. The first method measured GFR using clearance kinetics of plasma FITC-inulin after a single bolus injection. Based on a two-compartment model, estimated GFR was 236.69 +/- 16.55 and 140.20 +/- 22.27 microl/min in male and female C57BL/6J mice, respectively. Total or (5/6) nephrectomy reduced inulin clearance to 0 or 32.80 +/- 9.32 microl/min, respectively. Conversely, diabetes mellitus induced by streptozotocin was associated with increased GFR. The other approach measured urinary inulin clearance using intraperitoneal microosmotic pumps to deliver FITC-inulin and metabolic cages to collect timed urine samples. This approach yielded similar GFR values of 211.11 +/- 26.56 and 157.36 +/- 20.02 microl/min in male and female mice, respectively. These studies demonstrate the feasibility of repeated nonisotopic measurement of inulin clearance in conscious mice.

Tumor suppressor genes (TSGs) are guardian genes that play important roles in controlling cell proliferation processes such as cell-cycle checkpoints and inducing apoptosis. Identification of these genes and understanding their functions are critical for further investigation of tumorigenesis. So far, many studies have identified numerous TSGs and illustrated their functions in various types of tumors or normal samples. Furthermore, accumulating evidence has shown that non-coding RNAs can act as TSGs to prevent the tumorigenesis processes. Therefore, there is a growing demand to integrate TSGs with large-scale experimental evidence (e.g. gene expression and epigenetic signatures) to provide a comprehensive resource for further investigation of TSGs and their molecular mechanisms in cancer. To achieve this goal, we first developed a comprehensive literature-based database called TSGene (tumor suppressor gene database), freely available at http://bioinfo.mc.vanderbilt.edu/TSGene/. In the current release, TSGene contains 716 human (637 protein-coding and 79 non-coding genes), 628 mouse and 567 rat TSGs curated from UniProtKB, the Tumor Associated Gene database and 5795 PubMed abstracts. Additionally, the TSGene provides detailed annotations for each TSG, such as cancer mutations, gene expressions, methylation sites, TF regulations and protein–protein interactions.

The crown-of-thorns starfish (COTS, the Acanthaster planci species group) is a highly fecund predator of reef-building corals throughout the Indo-Pacific region 1 . COTS population outbreaks cause substantial loss of coral cover, diminishing the integrity and resilience of reef ecosystems 2-6 . Here we sequenced genomes of COTS from the Great Barrier Reef, Australia and Okinawa, Japan to identify gene products that underlie species-specific communication and could potentially be used in biocontrol strategies. We focused on water-borne chemical plumes released from aggregating COTS, which make the normally sedentary starfish become highly active. Peptide sequences detected in these plumes by mass spectrometry are encoded in the COTS genome and expressed in external tissues. The exoproteome released by aggregating COTS consists largely of signalling factors and hydrolytic enzymes, and includes an expanded and rapidly evolving set of starfish-specific ependymin-related proteins. These secreted proteins may be detected by members of a large family of olfactory-receptor-like G-protein-coupled receptors that are expressed externally, sometimes in a sex-specific manner. This study provides insights into COTS-specific communication that may guide the generation of peptide mimetics for use on reefs with COTS outbreaks.COTS are extremely fecund mass spawners 7 , which predisposes them to population outbreaks that result in a pronounced loss of live coral cover and associated biodiversity. These outbreaks have a higher impact on reef health and resilience than the combined effects of coral bleaching and disease, and increase the susceptibility of reefs to other potentially detrimental events, such as severe storms [2][3][4][5][6] (Supplementary Note 1).Although a range of local in situ control measures have been applied with some success (Supplementary Note 1), mitigation of COTS outbreaks on the necessary regional scale requires mass-deployed, species-specific strategies. In this context, genome-encoded COTSspecific attractants that underpin spawning aggregations have substantial potential as biocontrol agents. To identify attractants, we sequenced the genomes of two wild-caught individuals separated by over 5,000 km, one from the Great Barrier Reef (GBR), Australia and the other from Okinawa (OKI), Japan (Fig. 1c, d and Extended Data Fig. 1). We also sequenced transcriptomes from external organs, and proteins released into the seawater by COTS that were aggregating or were in the presence of their main predator, the giant triton Charonia tritonis (Fig. 1b).We generated separate 384 megabase (Mb) draft assemblies for the GBR and OKI genomes (Extended Data COTS genes are labelled and are marked with red lines; other asteroids, two shades of orange and yellow lines; sea urchins, dark green; hemichordates, light green; molluscs, pink; annelids, purple; cnidarians, black; and vertebrates, blue. The three clades to which COTS sequences belong are indicated by the outer circle. The asterisk denotes the fish-specific tru...

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Autism spectrum disorder (ASD) is a heterogeneous neurodevelopmental disorder with a prevalence of 0.9–2.6%. Twin studies showed a heritability of 38–90%, indicating strong genetic contributions. Yet it is unclear how many genes have been associated with ASD and how strong the evidence is. A comprehensive review and analysis of literature and data may bring a clearer big picture of autism genetics. We show that as many as 2193 genes, 2806 SNPs/VNTRs, 4544 copy number variations (CNVs) and 158 linkage regions have been associated with ASD by GWAS, genome-wide CNV studies, linkage analyses, low-scale genetic association studies, expression profiling and other low-scale experimental studies. To evaluate the evidence, we collected metadata about each study including clinical and demographic features, experimental design and statistical significance, and used a scoring and ranking approach to select a core data set of 434 high-confidence genes. The genes mapped to pathways including neuroactive ligand–receptor interaction, synapse transmission and axon guidance. To better understand the genes we parsed over 30 databases to retrieve extensive data about expression patterns, protein interactions, animal models and pharmacogenetics. We constructed a MySQL-based online database and share it with the broader autism research community at http://autismkb.cbi.pku.edu.cn, supporting sophisticated browsing and searching functionalities.