Genetic and functional characterization of disease associations explains comorbidity

Understanding relationships between diseases, such as comorbidities, has important socio-economic implications, ranging from clinical study design to health care planning. Most studies characterize disease comorbidity using shared genetic origins, ignoring pathway-based commonalities between diseases. In this study, we define the disease pathways using an interactome-based extension of known disease-genes and introduce several measures of functional overlap. The analysis reveals 206 significant links among 94 diseases, giving rise to a highly clustered disease association network. We observe that around 95% of the links in the disease network, though not identified by genetic overlap, are discovered by functional overlap. This disease network portraits rheumatoid arthritis, asthma, atherosclerosis, pulmonary diseases and Crohn's disease as hubs and thus pointing to common inflammatory processes underlying disease pathophysiology. We identify several described associations such as the inverse comorbidity relationship between Alzheimer's disease and neoplasms. Furthermore, we investigate the disruptions in protein interactions by mapping mutations onto the domains involved in the interaction, suggesting hypotheses on the causal link between diseases. Finally, we provide several proof-of-principle examples in which we model the effect of the mutation and the change of the association strength, which could explain the observed comorbidity between diseases caused by the same genetic alterations

Genome-wide characterization and expression profiling of HD-Zip gene family related to abiotic stress in cassava

<div><p>Homeodomain-leucine zipper (HD-Zip) gene family plays important roles in various abiotic stresses and hormone signaling in plants. However, no information is currently available regarding this family in cassava (<i>Manihot esculenta</i>), an important drought-tolerant crop in tropical and sub-tropical areas. Here, 57 <i>HD-Zip</i> genes (<i>MeHDZ01-57</i>) were identified in the cassava genome, and they were classified into four subfamilies based on phylogenetic analysis, which was further supported by their gene structure and conserved motif characteristics. Of which five gene pairs were involved in segmental duplication but none for tandem duplication, suggesting that segmental duplication was the main cause for the expansion of <i>MeHDZ</i> gene family in cassava. Global expression profiles revealed that <i>MeHDZ</i> genes were constitutively expressed, or not expressed, or tissue-specific expressed in examined tissues in both cultivated and wild subspecies. Transcriptomic analysis of three genotypes showed that most of <i>MeHDZ</i> genes responded differently to drought and polyethylene glycol treatments. Subsequently, quantitative RT-PCR analysis revealed comprehensive responses of twelve selected <i>MeHDZ</i> genes to various stimuli including cold, salt, and ABA treatments. These findings will increase our understanding of <i>HD-Zip</i> gene family involved in abiotic stresses and signaling transduction, and will provide a solid base for further functional characterization of <i>MeHDZ</i> genes in cassava.</p></div

Exon-intron structure of 57 <i>MeHDZ</i> genes in cassava.

<p>The phylogenetic tree was constructed by Maximum-Likelihood method with 1000 bootstrap replicates. The <i>MeHDZ</i> genes were clustered into four groups, I to IV. Exon-intron analysis was performed using GSDS (<a href="http://gsds.cbi.pku.edu.cn/" target="_blank">http://gsds.cbi.pku.edu.cn/</a>). Length of exons and introns of each <i>MeHDZ</i> gene was displayed proportionally. Upstream was defined as the sequences before the transcription start site ‘ATG’, while downstream was defined as the sequences after the stop codon (e.g., ‘TAA’).</p

Relative expression of <i>MeHDZ</i> genes in leaves under NaCl treatment.

<p>NTC (no treatment control) was normalized as “1” at each graph. Data were shown as mean ± standard deviation derived from three biological replicates, and values with different letters were significant based on Duncan’s multiple range tests (<i>P</i> < 0.05, n = 3).</p

Expression profiles of <i>MeHDZ</i> genes in cassava.

<p>(A) Expression of <i>MeHDZ</i> genes in different tissues of three genotypes. Log2-transformed FPKM value was used to plot the heatmap. ESR: early storage root; MSR: middle storage root; LSR: last storage root. (B) Expression of <i>MeHDZ</i> genes in response to drought and PEG treatments. Log2 based fold change of treatment/control was used to plot the heatmap. FL: folded leaf; FEL: full expanded leaf; BL: bottom leaf; RT: root. The numbers attached behind samples represented the time points at which samples were collected: e.g., 03 and 24 represented 3 and 24 h, respectively.</p

Conserved motifs of MeHDZ proteins corresponding to their phylogenetic relationships.

<p>The conserved motifs were identified by MEME software. Motifs were indicated by different colored boxes with the motif number, while non-conserved sequences were represented by grey lines. Length of motifs was exhibited proportionally.</p

Relative expression of <i>MeHDZ</i> genes in leaves under ABA treatment.

<p>NTC (no treatment control) was normalized as “1” at each graph. Data were shown as mean ± standard deviation derived from three biological replicates, and values with different letters were significant based on Duncan’s multiple range tests (<i>P</i> < 0.05, n = 3).</p

Physical locations of <i>MeHDZ</i> genes on cassava chromosomes.

<p>Chromosome numbers were indicated at the top of each chromosome. <i>MeHDZ</i> genes from different subfamilies were indicated by different colors. Five pairs of <i>MeHDZ</i> genes connected by dash lines were resulted from segmental duplication.</p

Additional file 1 of Targeting histone demethylases JMJD3 and UTX: selenium as a potential therapeutic agent for cervical cancer

Additional file 1: Table S1. Primers used for the qPCR assay; Table S2. Primers used for the ChIP-qPCR assay

Genome survey sequencing of Dracaena cambodiana

Dragon<a>’</a>s blood from the genus <i>Dracaena</i> is<b> </b>used as a renowned traditional medicine in various cultures worldwide. As an important original plant in tropical and subtropical areas, <i>D. cambodiana</i> remains poorly described at a genomic level, which impede research on the mechanism of dragon’s blood formation. This is the <i>Dracaena cambodiana</i> genome assembly via survey sequencing