PhastWeb: a web interface for evolutionary conservation scoring of multiple sequence alignments using phastCons and phyloP

Ramani, Ritika; Krumholz, Katie; Huang, Yi; Siepel, Adam

doi:10.1093/bioinformatics/bty966

Cited by 52 publications

(38 citation statements)

References 4 publications

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“…P-values were corrected for multiple testing using the Benjamini-Hochberg method (36) and sites with a corrected p-value less than 0.05 were considered significant. PhyloFit and phyloP are both part of the PHAST package v1.4 (85,86) . Figure 1.…”

Section: Methodsmentioning

confidence: 99%

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

Damas¹,

Hughes

Keough³

et al. 2020

Preprint

162

241

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The novel coronavirus SARS-CoV-2 is the cause of Coronavirus Disease-2019 (COVID-19). The main receptor of SARS-CoV-2, angiotensin I converting enzyme 2 (ACE2), is now undergoing extensive scrutiny to understand the routes of transmission and sensitivity in different species. Here, we utilized a unique dataset of 410 vertebrates, including 252 mammals, to study cross-species conservation of ACE2 and its likelihood to function as a SARS-CoV-2 receptor. We designed a five-category ranking score based on the conservation properties of 25 amino acids important for the binding between receptor and virus, classifying all species from very high to very low . Only mammals fell into the medium to very high categories, and only catarrhine primates in the very high category, suggesting that they are at high risk for SARS-CoV-2 infection. We employed a protein structural analysis to qualitatively assess whether amino acid changes at variable residues would be likely to disrupt ACE2/SARS-CoV-2 binding, and found the number of predicted unfavorable changes significantly correlated with the binding score. Extending this analysis to human population data, we found only rare (<0.1%) variants in 10/25 binding sites. In addition, we observed evidence of positive selection in ACE2 in multiple species, including bats. Utilized appropriately, our results may lead to the identification of intermediate host species for SARS-CoV-2, justify the selection of animal models of COVID-19, and assist the conservation of animals both in native habitats and in human care.

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Section: Methodsmentioning

confidence: 99%

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

Damas¹,

Hughes

Keough³

et al. 2020

Preprint

162

241

View full text Add to dashboard Cite

show abstract

“…Use a silent mutation to destroy the PAM sequence if possible, or use two silent mutations near the 3 end of the guide sequence (Cong et al, 2013). Check the evolutionary conservation of the wobble nucleotides (Ramani, Krumholz, Huang, & Siepel, 2019) to prioritize less conserved nucleotides. Check a codon usage chart to prioritize codons used at a similar frequency to the replaced codon (Athey et al, 2017).…”

Section: Designing Primers For the C-terminal Hdr Constructmentioning

confidence: 99%

ARF‐AID: A Rapidly Inducible Protein Degradation System That Preserves Basal Endogenous Protein Levels

Sathyan

Scott

Guertin

2020

CP Molecular Biology

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Inducible degron systems are widely used to specifically and rapidly deplete proteins of interest in cell lines and organisms. An advantage of inducible degradation is that the biological system under study remains intact and functional until perturbation, a feature that necessitates that the endogenous levels of the protein are maintained. However, endogenous tagging of genes with auxin-inducible degrons (AID) can result in chronic, auxin-independent proteasome-mediated degradation. The ARF-AID (auxin-response factorauxin-inducible degron) system is a re-engineered auxin-inducible protein degradation system. The additional expression of the ARF-PB1 domain prevents chronic, auxin-independent degradation of AID-tagged proteins while preserving rapid auxin-induced degradation of tagged proteins. Here, we describe the protocol for engineering human cell lines to implement the ARF-AID system for specific and inducible protein degradation. These methods are adaptable and can be extended from cell lines to organisms.

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“…The TFBS enrichment analysis was carried out using the plant regulatory data and analysis platform PlantRegMap [89], which contains 2177 transcription factors (1867 loci) classified into 58 families and their respective targets for P. vulgaris [89]. Initially, TFBSs in the promoter region (transcription start site + 500 bp -~100 bp) of common bean genes were detected using three methods: (i) motif: FIMO [90] was used to identify the high-quality binding motifs of a transcription factor with threshold 1 × 10 -5 , and a potential interaction was assigned if there was at least one binding site in the promoter of the gene; (ii) motif + conserved elements (motif_CE): an interaction was assigned only if more than 50% length of a binding site overlaps to conserved elements (identified by RPHAST [91]; and (iii) FunTFBS: an interaction was assigned only if there was at least one functional binding site (identified by the FunTFBS method [89]) in the promoter of the gene. Afterwards, common bean genes homologous to those from Arabidopsis reported by Mizzotti et al [41] were used to perform a TFBS enrichment analysis.…”

Section: Enrichment Analysis Of Transcription Factor Binding Sites (Tmentioning

confidence: 99%

Transcriptional Dynamics and Candidate Genes Involved in Pod Maturation of Common Bean (Phaseolus vulgaris L.)

Gómez-Martín

Capel

González

et al. 2020

Plants

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Pod maturation of common bean relies upon complex gene expression changes, which in turn are crucial for seed formation and dispersal. Hence, dissecting the transcriptional regulation of pod maturation would be of great significance for breeding programs. In this study, a comprehensive characterization of expression changes has been performed in two common bean cultivars (ancient and modern) by analyzing the transcriptomes of five developmental pod stages, from fruit setting to maturation. RNA-seq analysis allowed for the identification of key genes shared by both accessions, which in turn were homologous to known Arabidopsis maturation genes and furthermore showed a similar expression pattern along the maturation process. Gene-expression changes suggested a role in promoting an accelerated breakdown of photosynthetic and ribosomal machinery associated with chlorophyll degradation and early activation of alpha-linolenic acid metabolism. A further study of transcription factors and their DNA binding sites revealed three candidate genes whose functions may play a dominant role in regulating pod maturation. Altogether, this research identifies the first maturation gene set reported in common bean so far and contributes to a better understanding of the dynamic mechanisms of pod maturation, providing potentially useful information for genomic-assisted breeding of common bean yield and pod quality attributes.Plants 2020, 9, 545 2 of 20 metabolites such as carotenoids and anthocyanins [7][8][9][10][11]. Likewise, jasmonate promotes senescence and plays an important role in chlorophyll degradation [12,13], which is synthesized from alpha-linolenic acid [14,15], suggesting that the accumulation of this acid during maturation is responsible for stimulating chlorophyll loss [16]. In addition, the increased accumulation of antioxidant and monoterpene is also an important feature of the fruit maturation process [17][18][19].Like most species of the Fabaceae (also named as Leguminosae) family, common bean (Phaseolus vulgaris L.) produces dry fruits in the form of a pod, which is a photosynthetically active organ that encloses the developing seeds and protects them from pests and pathogens. Indeed, photosynthetically active pod tissue contributes to fuel seed growth with assimilates and nutrients [20]. As in most angiosperms, significant genetic, biochemical, and physiological changes take place during fruit maturation, which confers the functional and morphological properties of this plant organ. Unlike members of the Brassicaceae family that produce pods (siliques) derived from two fused carpels, legume pods are developed from a single carpel that emerges from the gynoecium after ovule fertilization. Subsequently, pods attain their maximum size through a growth phase caused by an active cell division and later cell expansion [21]. During the maturation phase, carbohydrate metabolism and amino acid biosynthesis are increased in pods, leading to the accumulation of storage compounds, mainly starch, total soluble amino acids, an...

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PhastWeb: a web interface for evolutionary conservation scoring of multiple sequence alignments using phastCons and phyloP

Cited by 52 publications

References 4 publications

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

Broad Host Range of SARS-CoV-2 Predicted by Comparative and Structural Analysis of ACE2 in Vertebrates

ARF‐AID: A Rapidly Inducible Protein Degradation System That Preserves Basal Endogenous Protein Levels

Transcriptional Dynamics and Candidate Genes Involved in Pod Maturation of Common Bean (Phaseolus vulgaris L.)

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