Advance articles alert 14 July 2019

**1.Identifying Emerging Phenomenon in Long Temporal Phenotyping Experiments
Jiajie Peng, Junya Lu, Donghee Hoh, Ayesha S Dina, Xuequn Shang, David M Kramer, Jin Chen
Bioinformatics, btz559, https://doi.org/10.1093/bioinformatics/btz559

Abstract
Motivation
The rapid improvement of phenotyping capability, accuracy, and throughput have greatly increased the volume and diversity of phenomics data（表型组学数据）. A remaining challenge is an efficient way to identify phenotypic patterns to improve our understanding of the quantitative variation of complex phenotypes, and to attribute gene functions. To address this challenge, we developed a new algorithm to identify emerging phenomena from large-scale temporal plant phenotyping experiments. An emerging phenomenon is defined as a group of genotypes who exhibit a coherent （连贯、相干、一致）phenotype pattern during a relatively short time. Emerging phenomena are highly transient（短暂的） and diverse, and are dependent in complex ways on both environmental conditions and development. Identifying emerging phenomena may help biologists to examine potential relationships among phenotypes and genotypes in a genetically diverse population and to associate such relationships with the change of environments or development.

Results
We present an emerging phenomenon identification tool called Temporal Emerging Phenomenon Finder (TEP-Finder). Using large-scale longitudinal（纵向的） phenomics data as input, TEP-Finder first encodes the complicated phenotypic patterns into a dynamic phenotype network. Then, emerging phenomena in different temporal scales are identified from dynamic phenotype network using a maximal clique based approach. Meanwhile, a directed acyclic network of emerging phenomena is composed to model the relationships among the emerging phenomena. The experiment that compares TEP-Finder with two state-of-art algorithms shows that the emerging phenomena identified by TEP-Finder are more functionally specific, robust, and biologically significant.

Availability
The source code, manual, and sample data of TEP-Finder are all available at: http://phenomics.uky.edu/TEP-Finder/.**

2.The Influence of Heterogeneous Codon Frequencies along Sequences on the Estimation of Molecular Adaptation
Roberto Del Amparo, Alberto Vicens, Miguel Arenas
Bioinformatics, btz558, https://doi.org/10.1093/bioinformatics/btz558
Published: 15 July 2019 Article history

Abstract
Motivation
The nonsynonymous/synonymous substitution rate ratio (dN/dS) is a commonly used parameter to quantify molecular adaptation in protein-coding data. It is known that the estimation of dN/dS can be biased if some evolutionary processes are ignored. In this concern, common ML methods to estimate dN/dS assume invariable codon frequencies among sites, despite this characteristic is rare in nature, and it could bias the estimation of this parameter.

Results
Here we studied the influence of variable codon frequencies among genetic regions on the estimation of dN/dS. We explored scenarios（场景、情景） varying the number of genetic regions that differ in codon frequencies, the amount of variability of codon frequencies among regions and the nucleotide frequencies at each codon position among regions. We found that ignoring heterogeneous codon frequencies among regions overall leads to underestimation of dN/dS and the bias increases with the level of heterogeneity of codon frequencies. Interestingly, we also found that varying nucleotide frequencies among regions at the first or second codon position leads to underestimation of dN/dS while variation at the third codon position leads to overestimation of dN/dS. Next, we present a methodology to reduce this bias based on the analysis of partitions presenting similar codon frequencies and we applied it to analyze four real datasets. We conclude that accounting for heterogeneous codon frequencies along sequences is required to obtain realistic estimates of molecular adaptation through this relevant evolutionary parameter.

Supplementary information
Supplementary data are available at Bioinformatics online.

3.DDT - Drug Discovery Tool: a fast and intuitive graphics user interface for Docking and Molecular Dynamics analysis
Simone Aureli, Daniele Di Marino, Stefano Raniolo, Vittorio Limongelli
Bioinformatics, btz543, https://doi.org/10.1093/bioinformatics/btz543

Abstract
Motivation
The ligand/protein binding interaction is typically investigated by docking（对接） and molecular dynamics （分子动力学）(MD) simulations. In particular, docking-based virtual screening (VS) is used to select the best ligands from database of thousands of compounds, while MD calculations assess the energy stability of the ligand/protein binding complexes. Considering the broad use of these techniques, it is of great demand to have one single software that allows a combined and fast analysis of VS and MD results. With this in mind, we have developed the Drug Discovery Tool (DDT) that is an intuitive graphics user interface able to provide structural data and physico-chemical information on the ligand/protein interaction.

Results
DDT is designed as a plugin for the Visual Molecular Dynamics (VMD) software and is able to manage a large number of ligand/protein complexes obtained from AutoDock4 (AD4) docking calculations and MD simulations（模拟）. DDT delivers 4 main outcomes: i) ligands （配体）ranking based on an energy score; ii) ligand ranking based on a ligands’ conformation cluster analysis; iii) identification of the aminoacids forming the most occurrent interactions with the ligands; iv) plot of the ligands’ center-of-mass coordinates in the cartesian space（欧几里得空间）. The flexibility of the software allows saving the best ligand/protein complexes using a number of user-defined options.

Availability
DDT_site_1 (alternative DDT_site_2); the DDT tutorial movie is available clicking here

Supplementary information
Supplementary data are available at Bioinformatics online.