Recent CIG publications Archive

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Nucleic Acids Res.: auth.: group Dessimoz

– 07/06/2020Posted in: Recent CIG publications
. 2020 Jul 2; 48(W1): W538–W545.
Published online 2020 May 6. doi: 10.1093/nar/gkaa308

The Quest for Orthologs benchmark service and consensus calls in 2020

Adrian M Altenhoff, Javier Garrayo-Ventas, Salvatore Cosentino, David Emms, Natasha M Glover, Ana Hernández-Plaza, Yannis Nevers, Vicky Sundesha, Damian Szklarczyk, José M Fernández, Laia Codó, the Quest for Orthologs Consortium, Josep Ll Gelpi, Jaime Huerta-Cepas, Wataru Iwasaki, Steven Kelly, Odile Lecompte, Matthieu Muffato, Maria J Martin, Salvador Capella-Gutierrez, Paul D Thomas, Erik Sonnhammer, and Christophe Dessimoz

ABSTRACT

The identification of orthologs—genes in different species which descended from the same gene in their last common ancestor—is a prerequisite for many analyses in comparative genomics and molecular evolution. Numerous algorithms and resources have been conceived to address this problem, but benchmarking and interpreting them is fraught with difficulties (need to compare them on a common input dataset, absence of ground truth, computational cost of calling orthologs). To address this, the Quest for Orthologs consortium maintains a reference set of proteomes and provides a web server for continuous orthology benchmarking (http://orthology.benchmarkservice.org). Furthermore, consensus ortholog calls derived from public benchmark submissions are provided on the Alliance of Genome Resources website, the joint portal of NIH-funded model organism databases.

PMCID: PMC7319555
PMID: 32374845
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Science Advances: auth.: group Dion and co-auth.: I.Xenarios

– 07/06/2020Posted in: Recent CIG publications
Science Advances  03 Jul 2020: Vol. 6, no. 27, eaaz4012 DOI: 10.1126/sciadv.aaz4012

Three-dimensional chromatin interactions remain stable upon CAG/CTG repeat expansion

Abstract

Expanded CAG/CTG repeats underlie 13 neurological disorders, including myotonic dystrophy type 1 (DM1) and Huntington’s disease (HD). Upon expansion, disease loci acquire heterochromatic characteristics, which may provoke changes to chromatin conformation and thereby affect both gene expression and repeat instability. Here, we tested this hypothesis by performing 4C sequencing at the DMPK and HTT loci from DM1 and HD–derived cells. We find that allele sizes ranging from 15 to 1700 repeats displayed similar chromatin interaction profiles. This was true for both loci and for alleles with different DNA methylation levels and CTCF binding. Moreover, the ectopic insertion of an expanded CAG repeat tract did not change the conformation of the surrounding chromatin. We conclude that CAG/CTG repeat expansions are not enough to alter chromatin conformation in cis. Therefore, it is unlikely that changes in chromatin interactions drive repeat instability or changes in gene expression in these disorders.

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Plant Physiol.: auth.: group Fankhauser

– 06/29/2020Posted in: Recent CIG publications

Abstract

Shade-avoiding plants, including Arabidopsis (Arabidopsis thaliana), display a number of growth responses, such as elongation of stem-like structures and repositioning of leaves, elicited by shade cues, including a reduction in the blue and red portions of the solar spectrum and a low red to far-red ratio. Shade also promotes phototropism of de-etiolated seedlings through repression of phytochrome B (phyB), presumably to enhance capture of unfiltered sunlight. Here we show that both low blue light and a low red to far-red light ratio are required to rapidly enhance phototropism in Arabidopsis seedlings. However, prolonged low blue light treatments are sufficient to promote phototropism through reduced cryptochrome 1 (cry1) activation. The enhanced phototropic response of cry1 mutants in the lab and in response to natural canopies depends on PHYTOCHROME INTERACTING FACTORs (PIFs). In favorable light conditions, cry1 limits the expression of PIF4, while in low blue light PIF4 expression increases, which contributes to phototropic enhancement. The analysis of quantitative DII-Venus, an auxin signaling reporter, indicates that low blue light leads to enhanced auxin signaling in the hypocotyl and, upon phototropic stimulation, a steeper auxin signaling gradient across the hypocotyl. We conclude that phototropic enhancement by canopy shade results from the combined activities of phytochrome B and cry1 that converge on PIF regulation.

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Curr Biol.: auth.: group Benton

– 06/29/2020Posted in: Recent CIG publications
Curr. Biol.: 2020 Jun 22;30(12):R710-R712.

Animal Behavior: A Neural Basis of Individuality

Suguru Takagi 1, Richard Benton 2

Abstract

Behavior can vary greatly even between genetically identical animals, but what determines such individuality? New work reveals that inter-individual differences in wiring of visual interneurons in Drosophila, arising from stochastic developmental events, underlie fly-specific object orientation abilities.

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Int J Mol Sci.: auth.: W. Wahli

– 06/29/2020Posted in: Recent CIG publications

Abstract

Peroxisome proliferator-activated receptor (PPAR)β/δ is a member of the nuclear receptor superfamily of transcription factors, which plays fundamental roles in cell proliferation and differentiation, inflammation, adipogenesis, and energy homeostasis. Previous studies demonstrated a reduced choroidal neovascularization (CNV) in Pparβ/δ-deficient mice. However, PPARβ/δ’s role in physiological blood vessel formation and vessel remodeling in the retina has yet to be established. Our study showed that PPARβ/δ is specifically required for disordered blood vessel formation in the retina. We further demonstrated an increased arteriovenous crossover and wider venous caliber in Pparβ/δ-haplodeficient mice. In summary, these results indicated a critical role of PPARβ/δ in pathological angiogenesis and blood vessel remodeling in the retina.

Keywords: PPARβ/δ; angiogenesis; arteriovenous crossover; blood vessel remodeling; pericytes; vessel caliber.

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Nat. Commun.: auth.: group Franken

– 06/22/2020Posted in: Recent CIG publications

Abstract

Sleep-wake driven changes in non-rapid-eye-movement sleep (NREM) sleep (NREMS) EEG delta (δ-)power are widely used as proxy for a sleep homeostatic process. Here, we noted frequency increases in δ-waves in sleep-deprived mice, prompting us to re-evaluate how slow-wave characteristics relate to prior sleep-wake history. We identified two classes of δ-waves; one responding to sleep deprivation with high initial power and fast, discontinuous decay during recovery sleep (δ2) and another unrelated to time-spent-awake with slow, linear decay (δ1). Reanalysis of previously published datasets demonstrates that δ-band heterogeneity after sleep deprivation is also present in human subjects. Similar to sleep deprivation, silencing of centromedial thalamus neurons boosted subsequent δ2-waves, specifically. δ2-dynamics paralleled that of temperature, muscle tone, heart rate, and neuronal ON-/OFF-state lengths, all reverting to characteristic NREMS levels within the first recovery hour. Thus, prolonged waking seems to necessitate a physiological recalibration before typical NREMS can be reinstated.

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