Embedding machine-readable proteins interactions data in scientific articles for easy access and retrieval

Extraction of protein-protein interactions data from scientific literature remains a hard, time- and resource-consuming task. This task would be greatly simplified by embedding in the source, i.e. research articles, a standardized, synthetic, machine-readable codification for protein-protein interactions data description, to make the identification and the retrieval of such very valuable information easier, faster, and more reliable than now.
We shortly discuss how this information can be easily encoded and embedded in research papers with the collaboration of authors and scientific publishers, and propose an online demonstrative tool that shows how to help and allow authors for the easy and fast conversion of such valuable biological data into an embeddable, accessible, computer-readable codification

Charting the NF-kB pathway interactome map

One of the phenomena observed in human aging is the progressive increase of a systemic inflammatory state, a condition referred to as “inflammaging”, negatively correlated with longevity. The five components of the Nuclear Factor kB (NF-kB) family are prominent mediators of inflammation. Several different signaling pathways activated by very diverse stimuli converge on NF-kB, resulting in a regulatory system characterized by high complexity. It is increasingly recognized that the number of components that impinges upon phenotypic outcomes of signal transduction pathways may be higher than those taken into consideration from canonical pathway representations. Scope of this analysis is to provide a wider, systemic picture of such intricate signaling system

Encoding the states of interacting proteins to facilitate biological pathways reconstruction

<p>Abstract</p> <p>Background</p> <p>In a systems biology perspective, protein-protein interactions (PPI) are encoded in machine-readable formats to avoid issues encountered in their retrieval for the reconstruction of comprehensive interaction maps and biological pathways. However, the information stored in electronic formats currently used doesn't allow a valid automatic reconstruction of biological pathways.</p> <p>Results</p> <p>We propose a logical model of PPI that takes into account the "state" of proteins before and after the interaction. This information is necessary for proper reconstruction of the pathway.</p> <p>Conclusions</p> <p>The adoption of the proposed model, which can be easily integrated into existing machine-readable formats used to store the PPI data, would facilitate the automatic or semi-automated reconstruction of biological pathways.</p> <p>Reviewers</p> <p>This article was reviewed by Dr. Wen-Yu Chung (nominated by Kateryna Makova), Dr. Carl Herrmann (nominated by Dr. Purificación López-García) and Dr. Arcady Mushegian.</p

Morphological and molecular genetic diversity of Syrian indigenous goat populations

Domestic goats in Syria may provide an interesting source of genetic variability due to its proximity to the centers of domestication. This study aimed to assess the morphological variation, genetic diversity and population substructure of the Syrian goat populations. Commonly, three goat genotypes are distinguished in Syria, namely Jabali or mountain goat, Baladi or local goat and Shami or Damascus (a well-known dairy goat). A pre-tested semi-structured questionnaire was used in recording both qualitative (coat color, eye color, horn length, horn orientation, nose profile) and quantitative (height  at wither, chest girth, cannon length, body length, ear length and ear width) morphological data. Data  from a total of 5,730 individual goats of the three goat populations reared in ten representative  provinces of Syria were collected and analyzed using GenStat version 14 statistical packages. Results of the morphological analysis confirmed that there were clear morphological variations among the three  goat populations. The three goat populations are mainly distinguished by their straight (Baladi, 71.1%  and Jabali, 82.8%) and curved (Shami, 89.5%) nose profiles. Substantial phenotypic variability was found among and within the breeds suggesting that these goat breeds have not yet undergone an organized breeding program. The genetic variability and population substructures from 398 individual animals of the three breeds were genotyped using 12 DNA microsatellite markers from Food and Agricultural Organization (FAO) panel. All microsatellites typed were found to be polymorphic and a total of 41 distinct alleles were detected on Baladi, Jabali and Shami goat populations. The Syrian goat populations had observed and expected heterozygosity values that ranged from 0.50 to 0.62 and 0.74 to 0.85, respectively, and an average of 13.97 alleles per locus across breeds. For all loci, an average inbreeding values (FIS) of low to moderate level was obtained across the three goat breeds, which ranged from 0.29 (Shami goats) to 0.34 (Baladi goats) indicating the absence of mating between close relatives within these populations. The observed positive FIS coefficients among the studied goat breeds also suggested heterozygote deficiencies. The analyses of the molecular data using STRUCURE program indicated there were two  primary populations, which did support the results based on morphological data of the same goat populations that clustered these goat populations into two main groups and confirmed the admixture nature of the Baladi and Jabali goat populations, while the Shami goat breed was well differentiated and grouped into a separate cluster that suggests its evolutionary and genetic uniqueness. The analysis of molecular variance (AMOVA) results detected genetic variations within individuals in a population (96%). The high genetic variability within individuals in a population provides a good base for  designing genetic improvement programs under the existing goat management systems.Key words: Characterization, cluster, genetic differentiation, population structure, Syria

A dual cis-regulatory code links IRF8 to constitutive and inducible gene expression in macrophages

The transcription factor (TF) interferon regulatory factor 8 (IRF8) controls both developmental and inflammatory stimulus-inducible genes in macrophages, but the mechanisms underlying these two different functions are largely unknown. One possibility is that these different roles are linked to the ability of IRF8 to bind alternative DNA sequences. We found that IRF8 is recruited to distinct sets of DNA consensus sequences before and after lipopolysaccharide (LPS) stimulation. In resting cells, IRF8 was mainly bound to composite sites together with the master regulator of myeloid development PU.1. Basal IRF8-PU.1 binding maintained the expression of a broad panel of genes essential for macrophage functions (such as microbial recognition and response to purines) and contributed to basal expression of many LPS-inducible genes. After LPS stimulation, increased expression of IRF8, other IRFs, and AP-1 family TFs enabled IRF8 binding to thousands of additional regions containing low-affinity multimerized IRF sites and composite IRF-AP-1 sites, which were not premarked by PU. 1 and did not contribute to the basal IRF8 cistrome. While constitutively expressed IRF8-dependent genes contained only sites mediating basal IRF8/PU.1 recruitment, inducible IRF8-dependent genes contained variable combinations of constitutive and inducible sites. Overall, these data show at the genome scale how the same TF can be linked to constitutive and inducible gene regulation via distinct combinations of alternative DNA-binding sites

High constitutive activity of a broad panel of housekeeping and tissue-specific cis-regulatory elements depends on a subset of ETS proteins

Enhancers and promoters that control the transcriptional output of terminally differentiated cells include cell type-specific and broadly active housekeeping elements. Whether the high constitutive activity of these two groups of cis-regulatory elements relies on entirely distinct or instead also on shared regulators is unknown. By dissecting the cis-regulatory repertoire of macrophages, we found that the ELF subfamily of ETS proteins selectively bound within 60 base pairs (bp) from the transcription start sites of highly active housekeeping genes. ELFs also bound constitutively active, but not poised, macrophage-specific enhancers and promoters. The role of ELFs in promoting high-level constitutive transcription was suggested by multiple evidence: ELF sites enabled robust transcriptional activation by endogenous and minimal synthetic promoters, ELF recruitment was stabilized by the transcriptional machinery, and ELF proteins mediated recruitment of transcriptional and chromatin regulators to core promoters. These data suggest that the co-optation of a limited number of highly active transcription factors represents a broadly adopted strategy to equip both cell type-specific and housekeeping cis-regulatory elements with the ability to efficiently promote transcription

AML1/ETO accelerates cell migration and impairs cell-to-cell adhesion and homing of hematopoietic stem/progenitor cells

The AML1/ETO fusion protein found in acute myeloid leukemias functions as a transcriptional regulator by recruiting co-repressor complexes to its DNA binding site. In order to extend the understanding of its role in preleukemia, we expressed AML1/ETO in a murine immortalized pluripotent hematopoietic stem/progenitor cell line, EML C1, and found that genes involved in functions such as cell-to-cell adhesion and cell motility were among the most significantly regulated as determined by RNA sequencing. In functional assays, AML1/ETO-expressing cells showed a decrease in adhesion to stromal cells, an increase of cell migration rate in vitro, and displayed an impairment in homing and engraftment in vivo upon transplantation into recipient mice. Our results suggest that AML1/ETO expression determines a more mobile and less adherent phenotype in preleukemic cells, therefore altering the interaction with the hematopoietic niche, potentially leading to the migration across the bone marrow barrier and to disease progression

Heme catabolism by tumor-associated macrophages controls metastasis formation

Although the pathological significance of tumor-associated macrophage (TAM) heterogeneity is still poorly understood, TAM reprogramming is viewed as a promising anticancer therapy. Here we show that a distinct subset of TAMs (F4/80hiCD115hiC3aRhiCD88hi), endowed with high rates of heme catabolism by the stress-responsive enzyme heme oxygenase-1 (HO-1), plays a critical role in shaping a prometastatic tumor microenvironment favoring immunosuppression, angiogenesis and epithelial-to-mesenchymal transition. This population originates from F4/80+HO-1+ bone marrow (BM) precursors, accumulates in the blood of tumor bearers and preferentially localizes at the invasive margin through a mechanism dependent on the activation of Nrf2 and coordinated by the NF-κB1–CSF1R–C3aR axis. Inhibition of F4/80+HO-1+ TAM recruitment or myeloid-specific deletion of HO-1 blocks metastasis formation and improves anticancer immunotherapy. Relative expression of HO-1 in peripheral monocyte subsets, as well as in tumor lesions, discriminates survival among metastatic melanoma patients. Overall, these results identify a distinct cancer-induced HO-1+ myeloid subgroup as a new antimetastatic target and prognostic blood marker