nprcgenekeepr v1.0.3

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Genetic Tools for Colony Management

Provides genetic tools for colony management and is a derivation of the work in Amanda Vinson and Michael J Raboin (2015) <https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4671785/> "A Practical Approach for Designing Breeding Groups to Maximize Genetic Diversity in a Large Colony of Captive Rhesus Macaques ('Macaca' 'mulatto')". It provides a 'Shiny' application with an exposed API. The application supports five groups of functions: (1) Quality control of studbooks contained in text files or 'Excel' workbooks and of pedigrees within 'LabKey' Electronic Health Records (EHR); (2) Creation of pedigrees from a list of animals using the 'LabKey' EHR integration; (3) Creation and display of an age by sex pyramid plot of the living animals within the designated pedigree; (4) Generation of genetic value analysis reports; and (5) Creation of potential breeding groups with and without proscribed sex ratios and defined maximum kinships.

Readme

README

R. Mark Sharp 05/17/2020

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nprcgenekeepr – Version 1.0.3 (20200526)

Introduction

The goal of nprcgenekeepr is to implement Genetic Tools for Colony Management. It was initially conceived and developed as a Shiny web application at the Oregon National Primate Research Center (ONPRC) to facilitate some of the analyses they perform regularly. It has been enhanced to have more capability as a Shiny application and to expose the functions so they can be used either interactively or in R scripts.

This work has been supported in part by NIH grants P51 RR13986 to the Southwest National Primate Research Center and P51 OD011092 to the Oregon National Primate Research Center.

At present, the application supports 5 functions:

  1. Quality control of studbooks contained in text files or Excel workbooks and of pedigrees within LabKey Electronic Health Records (EHR)
  2. Creation of pedigrees from a lists of animals using the LabKey EHR integration
  3. Creation and display of an age by sex pyramid plot of the living animals within the designated pedigree
  4. Generation of Genetic Value Analysis Reports
  5. Creation of potential breeding groups with and without proscribed sex ratios and defined maximum kinships.

For more information see:
A Practical Approach for Designing Breeding Groups to Maximize Genetic Diversity in a Large Colony of Captive Rhesus Macaques (Macaca mulatto) Vinson, A ; Raboin, MJ Journal Of The American Association For Laboratory Animal Science, 2015 Nov, Vol.54(6), pp.700-707 [Peer Reviewed Journal]

Installation

You can install the development version of nprcgenekeepr from GitHub from the R console prompt with:

install.packages("devtools")
devtools::install_github("rmsharp/nprcgenekeepr")

All missing dependencies should be automatically installed.

Online Documentation

You can find the complete online documentation at https://rmsharp.github.io/nprcgenekeepr/.

At the top of the page are three menus to the right of the Home icon: Reference, Articles, and Changelog.

The Reference menu at the top of the page brings up the list of documentation for Data objects, Major Features and Functions, Primary interactive functions and All exposed functions.

The Articles menu brings up the list of vignettes, which are, except for Development Plans, tutorials for using the package.

The Changelog brings up a copy of the NEWS file of the package, which records the major changes made for each version.

Running Shiny Application

The toolset available within nprcgenekeepr can be used inside standard R scripts. However, it was originally designed to be used within a Shiny application that can be started with:

library(nprcgenekeepr)
runGeneKeepR()

Summary of Major Functions

Quality Control

Studbooks maintained by breeding colonies generally contain information of varying quality. The quality control functions of the toolkit check to ensure all animals listed as parents have their own line entries, all parents have the appropriate sex listed, no animals are listed as both a sire and a dam, duplicate entries are removed, pedigree generation numbers are added, and all dates are valid dates. In addition, exit dates are added if possible and are consistent with other information such as departure dates and death dates. Current ages of animals that are still alive are added if a database connection is provided via a configuration file and the user has read permission on a LabKey server with the demographic data in an EHR (Electronic Health Record) module. See

Parents with ages below a user selected threshold are identified. A minimum parent age in years is set by the user and is used to ensure each parent is at least that age on the birth date of an offspring. The minimum parent age defaults to 2 years. This check is not performed for animals with missing birth dates.

Creation of Pedigree From a List of Potential Breeders and LabKey Integration

The user can enter a list of focal animals in a CSV file that will be used to create a pedigree containing all direct relative (ancestors and descendants) via the labkey.selectRows function within the Rlabkey package if a database connection is provided via a configuration file and the user has read permission on a LabKey server with the demographic data in an EHR (Electronic Health Record) module.

Two configuration files are needed to use the database features of nprcgenekeepr with LabKey. The first file is named _netrc on Microsoft Windows operating systems and .netrc otherwise, allows the user to authenticate with LabKey through the LabKey API and is fully described by LabKey documentation

The second file is named _nprcgenekeepr_config on Microsoft Windows operating systems and .nprcgenekeepr_config otherwise and is the nprcgenekeepr configuration file An image of this example configuration file is included as a data object and can be loaded and viewed with the following lines of R code in the R console.

data("exampleNprcgenekeeprConfig")
View(exampleNprcgenekeeprConfig)

Display of an age by sex pyramid plot

Adapted from on 20190603. Written by Matt Rosenberg. Updated May 07, 2019

The most important demographic characteristic of a population is its age-sex structure. Age-sex pyramids (also known as population pyramids) graphically display this information to improve understanding and make comparison easy. The population pyramid sometimes has a distinctive pyramid-like shape when displaying a growing population.

How to Read the Age-Sex Graph

An age-sex pyramid breaks down a population into male and female genders and age ranges. Usually, you’ll find the left side of the pyramid graphing the male population and the right side of the pyramid displaying the female population.

Along the horizontal axis (x-axis) of a population pyramid, the graph displays the population either as a total population of that age or as a percentage of the population at that age. The center of the pyramid starts at zero population and extends out to the left for males and right for females in increasing size, or proportion of the population.

Along the vertical axis (y-axis), age-sex pyramids display two-year age increments, from birth at the bottom to old age at the top.

Genetic Value Analysis Reports

The Genetic Value Analysis is a ranking scheme developed at ONPRC to indicate the relative breeding value of animals in the colony. The scheme uses the mean kinship for each animal to indicate how inter-related it is with the rest of the current breeding colony members. Genome uniqueness is used to provide an indication of whether or not an animal is likely to possess alleles at risk of being lost from the colony. Under the scheme, animals with low mean kinship or high genome uniqueness are ranked more highly.

Breeding Group Formation

One of the goals in breeding group formation is to avoid the potential for mating of closely related animals. Since behavioral concerns and housing constraints will also be taken into account in the group formation process, it is our goal to provide the largest number of animals possible from a list of candidates that can be housed together without risk of consanguineous mating. To that end, this function uses information from the Genetic Value Analysis to search for the largest combinations of animals that can be produced from a list of candidates.

The default options do not consider the sex of individuals when forming the groups, though this has likely been a consideration by the user in selecting the candidate group members. Optionally the user may select to form harem groups, which considers the sex of individuals when forming groups and restricts the number of males to one per group.

For more information see:
A Practical Approach for Designing Breeding Groups to Maximize Genetic Diversity in a Large Colony of Captive Rhesus Macaques (Macaca mulatto) Vinson, A ; Raboin, MJ Journal Of The American Association For Laboratory Animal Science, 2015 Nov, Vol.54(6), pp.700-707 [Peer Reviewed Journal]

Functions in nprcgenekeepr

Name Description
addIdRecords addIdRecords Adds Ego records added having NAs for parent IDs
addSexAndAgeToGroup Forms a dataframe with Id, Sex, and current Age given a list of Ids and a pedigree
addParents Add parents
calcFG Calculates Founder Genome Equivalents
calcFEFG Calculates Founder Equivalents and Founder Genome Equivalents
calcGU Calculates genome uniqueness for each ID that is part of the population.
calcRetention Calculates Allelic Retention
alleleFreq Calculates the count of each allele in the provided vector.
allTrueNoNA Returns TRUE if every member of the vector is TRUE.
calcAge Calculate animal ages.
calcA Calculates a, the number of an individual's alleles that are rare in each simulation.
checkChangedColsLst checkChangedColsLst examines list for non-empty fields
assignAlleles Assign parent alleles randomly
checkRequiredCols Examines column names, cols for required column names
calcFE Calculates founder Equivalents
checkErrorLst checkErrorLst examines list for non-empty fields
calculateSexRatio Calculates the sex ratio (number of non-males / number of males) given animal Ids and their pedigree
checkChangedColAndErrorLst checkChangedColAndErrorLst examines errorLst for errors and errorLst$changeCols non-empty fields
countLoops Count the number of loops in a pedigree tree.
chooseDate Choose date based on earlier flag.
chooseAllelesChar Combines two vectors of alleles when alleles are character vectors.
convertSexCodes Converts sex indicator for an individual to a standardized codes.
createPedOne createPedOne makes the pedOne data object
convertAncestry Converts the ancestry information to a standardized code
colChange colChange internal function to describe column names transformation
chooseAlleles Combines two vectors of alleles by randomly selecting one allele or the other at each position.
checkGenotypeFile Check genotype file
correctParentSex Sets sex for animals listed as either a sire or dam.
examplePedigree examplePedigree is a pedigree object created by qcStudbook
checkParentAge Check parent ages to be at least minParentAge
convertStatusCodes Converts status indicators to a Standardized code
fillBins fillBins Fill bins represented by list of two lists males and females.
convertDate Converts date columns formatted as characters to be of type datetime
createPedTree Create a pedigree tree (PedTree).
countFirstOrder Count first-order relatives.
fillGroupMembers Forms and fills list of animals groups based on provided constraints
findGeneration Determines the generation number for each id.
filterAge Removes kinship values where an animal is less than the minAge
getAncestors Recursively create a character vector of ancestors for an individual ID.
filterKinMatrix Filters a kinship matrix to include only the egos listed in 'ids'
create_wkbk Creates an Excel workbook with worksheets.
fillGroupMembersWithSexRatio Forms breeding group(s) with an effort to match a specified sex ratio
dataframe2string dataframe2string converts a data.frame object to a character vector
filterPairs Filters kinship values from a long-format kinship table based on the sexes of the two animals involved.
exampleNprcgenekeeprConfig exampleNprcgenekeeprConfig is a loadable version of the example configuration file example_nprcgenekeepr_config
findLoops Find loops in a pedigree tree
filterThreshold Filters kinship to remove rows with kinship values less than the specified threshold
getCurrentAge Age in years using the provided birthdate.
createPedSix createPedSix makes the pedSix data object
getDateColNames Vector of date column names
finalRpt finalRpt is a list object created from the list object rpt prepared by reportGV. It is created inside orderReport. This version is at the state just prior to calling rankSubjects inside orderReport.
getAnimalsWithHighKinship Forms a list of animal Ids and animals related to them
getDateErrorsAndConvertDatesInPed Converts columns of dates in text form to Date object columns
filterReport Filters a genetic value report down to only the specified animals
getChangedColsTab getChangedColsTab skeleton of list of errors
getDemographics Get demographic data
getDatedFilename Returns a character vector with an file name having the date prepended.
getMaxAx Get the maximum of the absolute values of the negative (males) and positive (female) animal counts.
get_elapsed_time_str Returns the elapsed time since start_time.
getMinParentAge Get minimum parent age.
getIncludeColumns Get the superset of columns that can be in a pedigree file.
getConfigFileName getConfigFileName returns the configuration file name appropriate for the system.
insertChangedColsTab insertChangedColsTab insert a list of changed columns found by qcStudbook in the pedigree file
getEmptyErrorLst Creates a empty errorLst object
get_and_or_list Returns a one element character string with correct punctuation for a list made up of the elements of the character vector argument.
getIdsWithOneParent getIdsWithOneParent extracts IDs of animals pedigree without either a sire or a dam
insertErrorTab insertErrorTab insert a list of errors found by qcStudbook in the pedigree file
getPotentialSires Provides list of potential sires
getPyramidPlot Creates a pyramid plot of the pedigree provided.
getPyramidAgeDist Get the age distribution for the pedigree
fixColumnNames fixColumnNames changes original column names and into standardized names.
hasBothParents hasBothParents checks to see if both parents are identified.
getRecordStatusIndex Returns record numbers with selected recordStatus.
getRequiredCols Get required column names for a studbook.
makeAvailable Convenience function to make the initial available animal list
lacy1989PedAlleles lacy1989PedAlleles is a dataframe produced by geneDrop on lacy1989Ped with 5000 iterations.
convertRelationships Converts pairwise kinship values to a relationship category descriptor.
findOffspring Finds the number of total offspring for each animal in the provided pedigree.
getGVGenotype Get Genetic Value Genotype data structure for reportGV function.
findPedigreeNumber Determines the generation number for each id.
getProbandPedigree Gets pedigree to ancestors of provided group leaving uninformative ancestors.
fixGenotypeCols Reformat names of observed genotype columns
hasGenotype Check for genotype data in dataframe
obfuscateDate obfucateDate adds a random number of days bounded by plus and minus max delta
getOffspring Get offspring to corresponding animal IDs provided
getGVPopulation Get the population of interest for the Genetic Value analysis.
getGenoDefinedParentGenotypes Assigns parental genotype contributions to an IDs genotype by attributing alleles to sire or dam
getProportionLow Get proportion of Low genetic value animals
getParamDef Get parameter definitions from tokens found in configuration file.
getProductionStatus Get production status of group
groupAddAssign Add animals to an existing breeding group or forms groups:
obfuscateId obfucateId creates a vector of ID aliases of specified length
pedDuplicateIds pedDuplicateIds is a dataframe with 9 rows and 5 columns (ego_id, sire, dam_id, sex, birth_date) representing a full pedigree with a duplicated record.
getGenotypes Get genotypes from file
groupMembersReturn Forms return list of groupAddAssign function
getLogo Get Logo file name
getLkDirectRelatives Get the direct ancestors of selected animals
getParents Get parents to corresponding animal IDs provided
getPedMaxAge Get the maximum age of live animals in the pedigree.
pedFemaleSireMaleDam pedFemaleSireMaleDam is a dataframe with 8 rows and 5 columns (ego_id, sire, dam_id, sex, birth_date) representing a full pedigree with the errors of having a sire labeled as female and a dam labeled as male.
getVersion getVersion Get the version number of nprcgenekeepr
getTokenList Gets tokens from character vector of lines
is_valid_date_str Returns TRUE if the string is a valid date.
print.summary.nprcgenekeeprErr print.summary.nprcgenekeepr print.summary.nprcgenekeeprGV
getSiteInfo Get site information
getSexRatioWithAdditions getSexRatioWithAdditions returns the sex ratio of a group.
kinMatrix2LongForm Reformats a kinship matrix into a long-format table.
insertSeparators insertSeparators inserts the character "-" between year and month and between month and day portions of a date string in %Y%m%d format.
qcBreeders qcBreeders is a list of 29 baboon IDs that are potential breeders
removeUnknownAnimals removeUnknownAnimals Removes unknown animals added to pedigree that serve as placeholders for unknown parents.
reportGV Generates a genetic value report for a provided pedigree.
makeCEPH Make a CEPH-style pedigree for each id
makeGrpNum Convenience function to make the initial grpNum list
makeGroupMembers Convenience function to make the initial groupMembers animal list
isEmpty Is vector empty or all NA values.
makesLoop makesLoop tests for a common ancestor.
mapIdsToObfuscated Map IDs to Obfuscated IDs
headerDisplayNames Convert internal column names to display or header names.
focalAnimals focalAnimals is a dataframe with one column (_id_) containing the of animal Ids from the __examplePedigree__ pedigree.
initializeHaremGroups Make the initial groupMembers animal list
geneDrop Gene drop simulation based on the provided pedigree information
makeExamplePedigreeFile Write copy of nprcgenekeepr::examplePedigree into a file
pedGood pedGood is a dataframe with 8 rows and 5 columns (ego_id, sire, dam_id, sex, birth_date) representing a full pedigree with no errors.
getFocalAnimalPed Get pedigree based on list of focal animals
getErrorTab getErrorTab skeleton of list of errors
getIndianOriginStatus Get Indian-origin status of group
removeDuplicates Remove duplicate records from pedigree
pedInvalidDates pedInvalidDates is a dataframe with 8 rows and 5 columns (ego_id, sire, dam_id, sex, birth_date) representing a full pedigree with values in the birth_date column that are not valid dates.
getPedigree Get pedigree from file
getLkDirectAncestors Get the direct ancestors of selected animals
removeEarlyDates removeEarlyDates removes dates before a specified year
getPossibleCols Get possible column names for a studbook.
removeUninformativeFounders Remove uninformative founders.
saveDataframesAsFiles Write copy of dataframes to either CSV or Excel file.
setExit Sets the exit date, if there is no exit column in the table
removeSelectedAnimalFromAvailableAnimals Updates list of available animals by removing the selected animal
orderReport Order the results of the genetic value analysis for use in a report.
ped1Alleles ped1Alleles is a dataframe created by the geneDrop function
makeRelationClassesTable Make relation classes table from kin dataframe.
qcPed qcPed is a dataframe with 277 rows and 6 columns
meanKinship Calculates the mean kinship for each animal in a kinship matrix
set_seed Work around for unit tests using sample() among various versions of R
setPopulation Population designation function
runGeneKeepR Allows running shiny application with nprcgenekeepr::runGeneKeepR()
nprcgenekeepr Genetic Management Functions
makeRoundUp Round up the provided integer vector int according to the modulus.
rhesusPedigree rhesusPedigree is a pedigree object
qcPedGvReport qcPedGvReport is a genetic value report
pedWithGenotype pedWithGenotype is a dataframe produced from qcPed by adding made up genotypes.
unknown2NA Removing IDs having "UNKNOWN" regardless of case
pedWithGenotypeReport pedWithGenotypeReport is a list containing the output of reportGV.
obfuscatePed obfuscatePed takes a pedigree object and creates aliases for all IDs and adjusts all date within a specified amount.
kinship Generates a kinship matrix.
lacy1989Ped lacy1989Ped small hypothetical pedigree
offspringCounts Finds the total number of offspring for each animal in the pedigree
withinIntegerRange Get integer within a range
pedMissingBirth pedMissingBirth is a dataframe with 8 rows and 5 columns (ego_id, sire, dam_id, sex, birth_date) representing a full pedigree with no errors.
resetGroup Update or add the "group" field of a Pedigree.
pedOne pedOne is a loadable version of a pedigree file fragment used for testing and demonstration
qcStudbook Quality Control for the Studbook or pedigree
pedSameMaleIsSireAndDam pedSameMaleIsSireAndDam is a dataframe with 8 rows and 5 columns (ego_id, sire, dam_id, sex, birth_date) representing a full pedigree with no errors.
toCharacter Force dataframe columns to character
trimPedigree Trim pedigree to ancestors of provided group by removing uninformative individuals
rhesusGenotypes rhesusGenotypes is a dataframe with two haplotypes per animal
rbindFill Append the rows of one dataframe to another.
removeGroupIfNoAvailableAnimals Remove group numbers when all available animals have been used
rankSubjects Ranks animals based on genetic value.
removePotentialSires Removes potential sires from list of Ids
pedSix pedSix is a loadable version of a pedigree file fragment used for testing and demonstration
readExcelPOSIXToCharacter Read in Excel file and convert POSIX dates to character
smallPed smallPed is a hypothetical pedigree
smallPedTree smallPedTree is a pedigree tree made from smallPed
str_detect_fixed_all Returns a logical vector with results of stri_detect() for each pattern in second parameters character vector.
summary.nprcgenekeeprErr summary.nprcgenekeeprErr Summary function for class nprcgenekeeprErr
addErrTxt Concatenates any errors from nprcgenekeeprErr into narrative form
agePyramidPlot Form age pyramid plot
addGroupOfUnusedAnimals addGroupOfUnusedAnimals adds a group to the saved groups if needed
addBackSecondParents Add back single parents trimmed pedigree
addAnimalsWithNoRelative Adds an NA value for all animals without a relative
addUIds Eliminates partial parentage situations by adding unique placeholder IDs for the unknown parent.
addGenotype Add genotype data to pedigree file
createExampleFiles Creates a folder with CSV files containing example pedigrees and ID lists used to demonstrate the package.
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Vignettes of nprcgenekeepr

Name
manual_components/_breeding_group_algorithm.Rmd
manual_components/_breeding_group_formation.Rmd
manual_components/_database_access.Rmd
manual_components/_genetic_value_analysis.Rmd
manual_components/_genome_uniqueness_algorithm.Rmd
manual_components/_gv_and_bg_desc.Rmd
manual_components/_input.Rmd
manual_components/_installation.Rmd
manual_components/_introduction.Rmd
manual_components/_online_documentation.Rmd
manual_components/_orip_reporting.Rmd
manual_components/_pedigree_browser.Rmd
manual_components/_running_shiny_application.Rmd
manual_components/_software_development.Rmd
manual_components/_summary_of_major_functions.Rmd
manual_components/_summary_statistics.Rmd
a2interactive.Rmd
a3manual.Rmd
a4Development_Plans.Rmd
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