rqt: an R package for gene-level meta-analysis.

MOTIVATION: Despite recent advances of modern GWAS methods, it is still remains an important problem of addressing calculation an effect size and corresponding p-value for the whole gene rather than for single variant. RESULTS: We developed an R package rqt, which offers gene-level GWAS meta-analysis. The package can be easily included into bioinformatics pipeline or used stand-alone. We applied this tool to the analysis of Alzheimer's disease data from three datasets CHS, FHS and LOADFS. Test results from meta-analysis of three Alzheimer studies show its applicability for association testing. AVAILABILITY AND IMPLEMENTATION: The package rqt is freely available under the following link: https://github.com/izhbannikov/rqt. CONTACT: ilya.zhbannikov@duke.edu. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

stpm: an R package for stochastic process model.

BACKGROUND: The Stochastic Process Model (SPM) represents a general framework for modeling the joint evolution of repeatedly measured variables and time-to-event outcomes observed in longitudinal studies, i.e., SPM relates the stochastic dynamics of variables (e.g., physiological or biological measures) with the probabilities of end points (e.g., death or system failure). SPM is applicable for analyses of longitudinal data in many research areas; however, there are no publicly available software tools that implement this methodology. RESULTS: We developed an R package stpm for the SPM-methodology. The package estimates several versions of SPM currently available in the literature including discrete- and continuous-time multidimensional models and a one-dimensional model with time-dependent parameters. Also, the package provides tools for simulation and projection of individual trajectories and hazard functions. CONCLUSION: In this paper, we present the first software implementation of the SPM-methodology by providing an R package stpm, which was verified through extensive simulation and validation studies. Future work includes further improvements of the model. Clinical and academic researchers will benefit from using the presented model and software. The R package stpm is available as open source software from the following links: https://cran.r-project.org/package=stpm (stable version) or https://github.com/izhbannikov/spm (developer version).

MetAmp: combining amplicon data from multiple markers for OTU analysis.

MOTIVATION: We present a novel method and corresponding application, MetAmp, to combine amplicon data from multiple genomic markers into Operational Taxonomic Units (OTUs) for microbial community analysis, calibrating the markers using data from known microbial genomes. When amplicons for multiple markers such as the 16S rRNA gene hypervariable regions are available, MetAmp improves the accuracy of OTU-based methods for characterizing bacterial composition and community structure. MetAmp works best with at least three markers, and is applicable to non-bacterial analyses and to non 16S markers. Our application and testing have been limited to 16S analysis of microbial communities. RESULTS: We clustered standard test sequences derived from the Human Microbiome Mock Community test sets and compared MetAmp and other tools with respect to their ability to recover OTUs for these benchmark bacterial communities. MetAmp compared favorably to QIIME, UPARSE and Mothur using amplicons from one, two, and three markers. AVAILABILITY AND IMPLEMENTATION: MetAmp is available at http://izhbannikov.github.io/MetAmp/.

Contributions of Women to Cardiovascular Science Over Two Decades: Authorship, Leadership, and Mentorship.

Background Women remain underrepresented in cardiology. We aimed to assess gender trends in research authorship, authorship in leading roles, mentorship, and research team diversity. Methods and Results We identified "cardiac and cardiovascular systems" journals from 2002 to 2020 using Journal Citation Reports 2019 (Web of Science, Clarivate Analytics). Gender authorship, mentorship, research team diversity, and trends were assessed. Associations between author gender and impact factor, journal region, and cardiology subspecialties were analyzed. Analysis of 396 549 research papers from 122 journals showed the percentage of women authors increased from 16.6% to 24.6% (ß=0.38 [95% CI, 0.29-0.46]; P<0.001), whereas the proportion of women first (ß=-0.03 [95% CI, -0.06 to 0.004]; P=0.09) or last authors (ß=-0.017 [95% CI, -0.04 to 0.006]; P=0.15) was unchanged. Compared with men last authors, women last authors were more likely to mentor women first authors and lead more diverse research teams (both P<0.001). Journal impact factor was related to percentage of women authors overall (Spearman's correlation coefficient RS=0.208 [95% CI, 0.02-0.38]; P=0.03) but not first or last women authors (both P>0.5). Women comprised 18.4%-25.7% of authors in cardiology subspecialties. Journal region and author gender were unrelated (all P>0.4). Conclusions Women's inclusion as authors of cardiology papers increased slightly over the past 2 decades, yet the proportions of women in first and last authorship roles were unchanged. Women are increasingly likely to mentor women first authors and lead diverse research teams. Women last authors are essential to increasing diversity of future independent investigators and inclusive research teams, both of which are associated with innovation and excellence in science.

"Physiological Dysregulation" as a Promising Measure of Robustness and Resilience in Studies of Aging and a New Indicator of Preclinical Disease.

Recently suggested novel implementation of the statistical distance measure (DM) for evaluating "physiological dysregulation" (PD) in aging individuals (based on measuring deviations of multiple biomarkers from baseline or normal physiological states) allows reducing high-dimensional biomarker space into a single PD estimate. Here we constructed DM using biomarker profiles from FRAMCOHORT (Framingham Heart Study) and CHS (Cardiovascular Health Study) Research Materials obtained from the NHLBI Biologic Specimen and Data Repository Information Coordinating Center, and estimated effect of PD on total survival, onset of unhealthy life (proxy for "robustness") and survival following the onset of unhealthy life (proxy for "resilience"). We investigated relationships between PD and declines in stress resistance and adaptive capacity not directly observed in data. PD was more strongly associated with the onset of unhealthy life than with survival after disease suggesting that declines in robustness and resilience with age may have overlapping as well as distinct mechanisms. We conclude that multiple deviations of physiological markers from their normal states (reflected in higher PD) may contribute to increased vulnerability to many diseases and precede their clinical manifestation. This supports potential use of PD in health care as a preclinical indicator of transition from healthy to unhealthy state.

cophesim: a comprehensive phenotype simulator for testing novel association methods.

Simulation is important in evaluating novel methods when input data is not easily obtainable or specific assumptions are needed. We present cophesim, a software to add the phenotype to generated genotype data prepared with a genetic simulator. The output of cophesim can be used as a direct input for different genome wide association study tools. cophesim is available from https://bitbucket.org/izhbannikov/cophesim.

haploR: an R package for querying web-based annotation tools.

We developed haploR, an R package for querying web based genome annotation tools HaploReg and RegulomeDB. haploR gathers information in a data frame which is suitable for downstream bioinformatic analyses. This will facilitate post-genome wide association studies streamline analysis for rapid discovery and interpretation of genetic associations.

SlopMap: a software application tool for quick and flexible identification of similar sequences using exact k-mer matching.

With the advent of Next-Generation (NG) sequencing, it has become possible to sequence a entire genomes quickly and inexpensively. However, in some experiments one only needs to extract and assembly a portion of the sequence reads, for example when performing transcriptome studies, sequencing mitochondrial genomes, or characterizing exomes. With the raw DNA-library of a complete genome it would appear to be a trivial problem to identify reads of interest. But it is not always easy to incorporate well-known tools such as BLAST, BLAT, Bowtie, and SOAP directly into a bioinformatics pipelines before the assembly stage, either due to incompatibility with the assembler's file inputs, or because it is desirable to incorporate information that must be extracted separately. For example, in order to incorporate flowgrams from a Roche 454 sequencer into the Newbler assembler it is necessary to first extract them from the original SFF files. We present SlopMap, a bioinformatics software utility that allows quickly identification similar to the provided reference reads from either Roche 454 or Illumnia DNA library. With simple and intuitive command-line interface along with file output formats compatible to assembly programs, SlopMap can be directly embedded to biological data processing pipeline without any additional programming work. In addition, SlopMap preserves flowgram information needed for Roche 454 assembler.