Gene networks in Drosophila melanogaster: integrating experimental data to predict gene function

The first computational interaction network built from Drosophila melanogaster protein-protein and genetic interaction data allows the functional annotation of orphan genes and reveals clusters of functionally-related genes

Massively parallel functional dissection of regulatory elements

Thesis (Ph.D.)--University of Washington, 2012

Anaesthetic Management of Laparoscopic Adrenalectomy for Adrenocortical Tumour in a Paediatric Patient ? A Case Report

Adrenocortical tumors are rare in children. An 8 months, 8kg child with Cushingoid features with persistent severe hypertension was admitted in pediatric surgery ward.Blood pressure was controlled by ACE inhibitors & calcium channel blockers. Diagnosis of adrenal tumor was confirmed by abdominal CT Scan. We report the management of this patient posted for laparoscopy adrenalectom

A novel hierarchically hybrid structure of MXene and bi‐ligand ZIF‐67 based trifunctional electrocatalyst for zinc‐air battery and water splitting

Abstract The development of cost‐effective and durable electrocatalysts possesses a broad spectrum of applications in sustainable energy systems. Herein, a hierarchical composite of Co‐based bi‐ligand zeolite imidazole framework (ZIF‐67) with highly conducting 2D MXene as highly efficient noble metal free electrocatalyst for electrochemical oxygen reduction reaction (ORR), complete water splitting, along with zinc‐air battery (ZAB) has been studied. ZIF‐67 is reported as an efficient electrocatalyst due to its porous structures, high surface area and atomically dispersed active metal centres while low conductivity and structural instability have been addressed by pyrolysis. In this work, structural disintegration due to temperature effect has been handled by using bi‐ligand linkers in ZIF (b‐ZIF‐67) which controls its sharp morphology and uniform mesoporous structure. This b‐ZIF‐67 has been supported on highly conducting 2D MXene material which exposes ample accessible active sites to accelerate the electroactivity of the synthesized catalyst. The resultant b‐CZIF‐67/MXene catalyst exhibits superior onset of 0.91 and 0.93 V in acidic and alkaline medium respectively for ORR. At the current density of 10 mA/cm2 catalyst shows a very low overpotential of 0.170 mV and 1.47 V for HER and OER, respectively. The excellent specific charge storage of 550.6 mAh/g was displayed by the homemade ZAB pouch

Massively parallel decoding of mammalian regulatory sequences supports a flexible organizational model

Despite continual progress in the cataloging of vertebrate regulatory elements, little is known about their organization and regulatory architecture. Here we describe a massively parallel experiment to systematically test the impact of copy number, spacing, combination and order of transcription factor binding sites on gene expression. A complex library of ∼5,000 synthetic regulatory elements containing patterns from 12 liver-specific transcription factor binding sites was assayed in mice and in HepG2 cells. We find that certain transcription factors act as direct drivers of gene expression in homotypic clusters of binding sites, independent of spacing between sites, whereas others function only synergistically. Heterotypic enhancers are stronger than their homotypic analogs and favor specific transcription factor binding site combinations, mimicking putative native enhancers. Exhaustive testing of binding site permutations suggests that there is flexibility in binding site order. Our findings provide quantitative support for a flexible model of regulatory element activity and suggest a framework for the design of synthetic tissue-specific enhancers

Systematic Dissection of Coding Exons at Single Nucleotide Resolution Supports an Additional Role in Cell-Specific Transcriptional Regulation

<div><p>In addition to their protein coding function, exons can also serve as transcriptional enhancers. Mutations in these exonic-enhancers (eExons) could alter both protein function and transcription. However, the functional consequence of eExon mutations is not well known. Here, using massively parallel reporter assays, we dissect the enhancer activity of three liver eExons (<i>SORL1</i> exon 17, <i>TRAF3IP2</i> exon 2, <i>PPARG</i> exon 6) at single nucleotide resolution in the mouse liver. We find that both synonymous and non-synonymous mutations have similar effects on enhancer activity and many of the deleterious mutation clusters overlap known liver-associated transcription factor binding sites. Carrying a similar massively parallel reporter assay in HeLa cells with these three eExons found differences in their mutation profiles compared to the liver, suggesting that enhancers could have distinct operating profiles in different tissues. Our results demonstrate that eExon mutations could lead to multiple phenotypes by disrupting both the protein sequence and enhancer activity and that enhancers can have distinct mutation profiles in different cell types.</p></div

Regulatory profiles of eExons in mouse liver and HeLa cells.

<p>Estimated effect sizes of all possible nucleotide substitutions based on coefficients from position variant (gray bars) models for each eExon. Multiple linear regressions with sets of ten adjacent positions as predictors were used to analyze the F-statistic of these models that represent the extent to which the model is predictive of the outcome (blue shadow). Both log2 of fold change relative to reference sequence (left; y-axes) and F-statistic (right; y-axes) are plotted for each eExon in mouse liver (A–C) and HeLa cells (D–F): <i>SORL1</i> exon 17 (A,D), <i>TRAF3IP2</i> exon 2 (B,E) and <i>PPARG</i> exon 6 (C,F). Significant effect mutation clusters with a differential profile between mouse liver and HeLa cells that overlap predicted HNF4A binding sites are illustrated by blue dotted rectangles, while mutation clusters that overlap predicted AP-1 binding sites and remained unchanged in both experiments are marked by red dotted rectangles.</p