Map of HIV-human protein complexes.

<p>40 identified human protein complexes are shown together with the HIV protein targeting the complex. Green rectangles correspond to HIV proteins. Human complexes are shown as ellipses. A color gradient from red (high) to yellow (low) indicates the average rank of the complex in the APMS- and RNAi-propagations. Node size corresponds to number of subunits in the complex. Gray edges represent functional interactions between the human complexes; green edges are HIV-human interactions. Purple boxes indicate protein complexes that were selected for follow-up RNAi screens.</p

Workflow Overview.

<p>HIV-interacting proteins and RNAi phenotypes are mapped to a network of human protein functional interactions (yellow and red nodes respectively). Network propagation is performed separately for each of these two mappings. Significant genes are selected based on the combination of both propagation results (blue nodes). Finally, enriched HIV-human protein complexes are identified within the list of significant genes (HIV proteins added as green nodes, protein complexes highlighted by circles).</p

Identification of genome-wide targets of Olig2 in the adult mouse spinal cord using ChIP-Seq

<div><p>In jawed vertebrates, oligodendrocytes (OLs) are the myelin-producing glial cells responsible for ensheathment of axons within the central nervous system and are also crucial for remyelination following injury or disease. Olig2 is a crucial factor in the specification and differentiation of oligodendrocyte precursor cells (OPCs) that give rise to mature, myelin-producing OLs in the developing and postnatal CNS; however, its role in adulthood is less well understood. To investigate the role Olig2 plays in regulating gene expression in the adult OL lineage in a physiologically-relevant context, we performed chromatin immunoprecipitation followed by next generation sequencing analysis (ChIP-Seq) using whole spinal cord tissue harvested from adult mice.</p><p>We found that many of the Olig2-bound sites were associated with genes with biological processes corresponding to OL differentiation (Nkx2.2, Nkx6.2, and Sip1), myelination and ensheathment (Mbp, Cldn11, and Mobp), as well as cell cycle and cytoskeletal regulation. This suggests Olig2 continues to play a critical role in processes related to OL differentiation and myelination well into adulthood.</p></div

Selected complexes and RNAi screening results.

<p>(A) Profilin-1 complex interacting with GP160. (B) DNA-PK-Ku-eIF2-NF90-NF20 complex interacting with NC. (C) LARC complex interacting with Gag. Interactions within the complex represent functional interactions from HumanNet (green), manually curated interactions from the Metabase resource (gray) or from both sources (red). Pink vs. turquoise stars correspond to proteins that were confirmed in our RNAi validation screen vs. previous screens, respectively. Orange nodes are kinases, red transcription factors, blue are binding proteins as classified in Metabase. The bar plots show the HIV luciferase activity of the sample normalized by the HIV luciferase activity of control siRNAs. (D) HIV luciferase activity for three non-targeting siRNAs (positive controls) and luciferase-targeting siGL3 (negative control) performed simultaneously with siRNA transfections shown in A, B, and C.</p

Functional GO terms overrepresented in the Olig2 ChIP-Seq dataset.

<p>Shown are the highest ranking terms for (A) Biological Processes, (B) Protein Class, and (C) Pathways according to PANTHER (geneontology.org) and ranked according enrichment score (FE; red bars) and statistical significance (-log2p-val; black line) as indicated.</p

Comparison of results from different studies.

<p>The table lists all protein complexes identified by our method, as well as the complexes identified in three previous analyses from Jaeger et al, Murali et al, and Bushman et al. Bold complexes correspond to those uniquely identified in our study, italic to those identified by us and by at least one previous study. The remainder corresponds to protein complexes identified in previous analyses only.</p

Validation of ChIP-Seq targets by ChIP-qPCR.

<p>(A) Box plot depicting enrichment over total genomic input (%Input) for both Olig2 ChIP (Olig2) and mock IgG (IgG) control conditions for 13 gene targets identified by ChIP-Seq. (B) IGV genome browser tracks showing the location of primers targeting either a specific ON-target peak summit (green bar; ON) or OFF-target region located 10–30 kb from the nearest peak (red bar; OFF) for Nkx2.2, Opalin, and Zcchc24. Results for all ChIP-qPCR data were generated from three independent experiments.</p

Tracking peripheral biomarkers identified from the causal mapping of PD brain.

<p>(<b>a</b>) High confidence biomarkers consistently identified for PD cortex, striatum, and substantia nigra (S. nigra) using microarray analysis. Upregulated biomarkers are shown on the left together with fold changes in the three brain regions, downregulated biomarkers on the right. (<b>b</b>) Functional biomarker panel that combines DEGs, high confidence biomarkers shown in (a) and genes from the causal map. (<b>c</b>) Assessment of biomarkers in brain (top panels)(substantia nigra, SN) and blood (bottom panels) from age-matched control and PD patients using QuantiGene technology from Panomics. * <i>p</i>≤0.05 and ** <i>p</i>≤0.01 as determined using a two-tailed unpaired t-test with Welch's correction.</p

Overlap between pathways significantly enriched with differentially expressed genes identified by microarray and RNA-sequencing.

<p>(<b>a</b>) Overlap of pathways enriched with upregulated genes together with the five most significant overlapping pathways. (<b>b</b>) Overlap of pathways enriched with downregulated genes together with the five most significant overlapping pathways.</p