Breeder selection in HS rats 🐀 💘 🐀

This repository contains R source code to select breeders in an outbred line so that inbreeding in the offspring is minimized. This repository was cloned from breedail, which was originally developed for advanced intercross lines in mice, and is currently used by the HS West colony, managed by Dr. Abraham Palmer's lab at UC San Diego, for breeding Heterogeneous Stock (HS) rats.

The core breedail algorithm is unchanged here, but this repository provides three main additions to the original breedail repo:

1. Utility functions to make breeder selection more user-friendly, without the need for substantial code and manual re-runs (such as in the original example code provided with breedail).

2. A novel algorithm for merging pedigrees following breeder exchanges between separate populations.

3. Functions to simulate forward breeding and breeder selection in theoretical future generations.

Background: HS rats 🐀

The HS West colony (HSW) was founded using HS rats provided to UCSD from Wake Forest University (WFU),from a subset of WFU generation 42. That is, some WFU generation 42 rats were used to produce WFU generation 43, and other WFU generation 42 rats were sent to HSW (event 'A' in the figure below). The HSW colony follows a naming convention that counts HSW generations based on the number of generations since the original founding of the HS rats strain, not since the founding of the WFU colony. So, WFU gen042 rats sent to HSW comprise HSW gen096. Both colonies have been maintained separately (with occasional exchanges of rats betweeen the two, see below), following separate generation times. As such, there is no direct equivalence between any WFU generations after WFU gen042 and any HSW generations after HSW gen096. While an HSW colony didn't exist prior to gen096, for the sake of a consistent numbering convention required for breedail, WFU generations before gen042 can also be considered HSW generations 54-95.

Colony exchanges

The two colonies regularly exchange animals to breed between them in order to minimize drift between colonies and maintain outbreeding across the greater HS rat population. These exchanges include:

• In March 2024, WFU sent 43 male rats to HSW (event 'B' above)
• In late 2025 (expected), HSW will send 50 gen107 males to incorporate into WFU gen052, in exchange for 44 WFU gen051 males, which will be incorporated into HSW gen108.

Different generation times and ID conventions between the colonies require a complicated merging algorithm in order to produce a joint pedigree usable for breedail. breedHS automates these merges to enable kinship estimation and breeder selection using breedail.

Files

• kinship.R defines functions to calculate and update pairwise kinship coefficients. These are core breedail functions unmodified from the original repository.

• find_mates.R defines functions to pair breeders in a given generation of the pedigree in such a way that they will produce the smallest average inbreeding coefficients in the offspring. These are core breedail functions unmodified from the original repository.

• breedHS.R defines pre- and post-processing functions to format data input and output from breedail, and wrapper functions to facilitate the execution of breedail's core algorithm. Many of these are generalizable to any population using breedail for kinship estimation and breeder selection, and/or any pair of populations for whom a common, joint pedigree is needed. Some important functions:

  • find.ped.errors Identifies IDs listed as parents in a given generation who are not found in the prior generation. Outputs IDs and relevant file paths to a file for ad-hoc investigation. More error checks are being tested for inclusion soon.
  • format.pedigree Reads multiple single-generation pedigree files for one population and formats them into a complete pedigree ready for input into breedail.
  • select.breeders integrates multiple breedail and breedHS functions to identify maximally-outbred breeder pairs given a set of pedigree files
  • mate.breeders Simulates breeding between a population of breeders output by breedail. Results can be appended to an existing pedigree to explore hypothetical future breeding scenarios.
  • merge.pedigrees Merges the distinct pedigrees of two separate populations into a common pedigree for input into breedail. Robust to differences in populations in their generation count and numbering convention, sample ID naming convention, and the number and direction (either one-directional or bidirectional) of exchanges.

The other functions in this script are useful for converting pedigrees between WFU and HSW-specific formatting conventions.

• HSW_utils.R defines pre- and post-processing functions specifically tailored to data formatting conventions at HSW. While these are not generalizable to other populations as-is, they may provide a useful template for other investigators interested in using breedail.

• WFU_utils.R defines pre- and post-processing functions specifically tailored to data formatting conventions at WFU. As above, they may provide a useful template for other investigators interested in using breedail.

Usage

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Code in the inst/ directory can be used as-is (after updating necessary arguments and input files) to execute pairing at either HSW or WFU under different pairing scenarios. These include:

• Regular HSW pairing during non-exchange generations
• Regular WFU pairing during non-exchange generations
• Pairing conducted at HSW when receiving/incorporating new rats from WFU
• Pairing conducted at WFU when receiving/incorporating new rats from HSW

Comprehensive examples for the above are currently in progress. Come back soon!
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