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README.md

SPhyR - Single-cell Phylogeny Reconstruction

SPhyR is an algorithm for reconstructing phylogenetic trees from single-cell sequencing data. SPhyR employs the k-Dollo phylogeny model, where each SNV can only be gained once but lost k times.

Overview of SPhyR

Contents

  1. Compilation instructions
  2. Usage instructions

Compilation instructions

Dependencies

SPhyR is written in C++11 and thus requires a modern C++ compiler (GCC >= 4.8.1, or Clang). In addition, SPhyR has the following dependencies.

Graphviz is required to visualize the resulting DOT files, but is not required for compilation.

In case doxygen is available, extended source code documentation will be generated.

Compilation

To compile SPhyR, execute the following commands from the root of the repository:

$ mkdir build
$ cd build
$ cmake ..
$ make

In case CMake fails to detect LEMON, run the following command with adjusted paths:

$ cmake -DLIBLEMON_ROOT=~/lemon 

The compilation results in the following files in the build directory:

EXECUTABLE DESCRIPTION
analyze Computes various performance statistics of a solution.
kDP Solves the k-Dollo Phylogeny problem given a binary matrix B and integer k.
kDPFC Solves the k-Dollo Phylogeny Flip and Clsuter problem given a binary matrix with missing data, an integer k, a false positve rate alpha, a false negative rate beta, a number s of taxon clusters and number t of character clusters.
perturb Introduces false positives and false negatives in a given binary matrix.
simulate Simulates a k-Dollo phylogenetic tree given a perfect phylogeny tree
visualize Visualizes a phylogenetic treein Graphviz DOT format.

Usage instructions

I/O formats

SPhyR's input file is text based. The first line lists the number of taxa (cells), followed by the number of characters (SNVs) on the second line. Then, each subsequent line defines the value of each character for each taxon. More specifically, the allowed values are 0, 1 and -1, where 0 denotes the absence of the mutation, 1 denotes the presence of the mutation and -1 indicates missing data.

k-Dollo Phylogeny (kDP)

In the k-Dollo Phylogeny problem, we are given a binary matrix B and integer k, and wish to determine whether there exists a k-Dollo phylogeny for B, and if so construct one.

Usage:
  ./kDP [--help|-h|-help] [-M int] [-T int] [-k int] [-t int] [-v] input
     output
Where:
  input
     Input file
  output
     Output file
  --help|-h|-help
     Print a short help message
  -M int
     Memory limit in MB (default: -1, unlimited)
  -T int
     Time limit in seconds (default: -1, unlimited)
  -k int
     Maximum number of losses per character (default: 1)
  -t int
     Number of threads (default: 1)
  -v
     Verbose output

An example execution:

$ ./kDP -k 1 ../data/k_dollo/m25_n25_s7_k1_loss0.4.B > outputA.txt
Step 1 -- elapsed time 0.00345898 s
Step 1 -- number of constraints: 138
Step 1 -- number of active variables: 54
Step 1 -- introduced 3 constraints
Step 2 -- elapsed time 0.00559616 s
Step 2 -- number of constraints: 141
Step 2 -- number of active variables: 58
Step 2 -- introduced 0 constraints
CPLEX: [2000 , 2000]
Elapsed time: 0.013164

The file outputA.txt contains the k-Dollo completion.

k-Dollo Phylogeny Flip and Cluster (kDPFC)

In the k-Dollo Phylogeny Flip and Cluster, we are given matrix D, error rates alpha, beta, integers k, s, t, and wish to find a binary matrix A and tree T such that: (1)~B has at most s unique rows and at most t unique columns; (2) \Pr(D \mid B, alpha, beta)$ is maximum; and (3) T is a k-Dollo phylogeny for B.

Usage:
  ./kDPFC [--help|-h|-help] [-M int] [-N int] [-T int] [-a num] [-b num]
     [-k int] [-s int] [-t int] [-v] input output
Where:
  input
     Input file
  output
     Output file
  --help|-h|-help
     Print a short help message
  -M int
     Memory limit in MB (default: -1, unlimited)
  -N int
     Number of restarts (default: 1)
  -T int
     Time limit in seconds (default: -1, unlimited).
  -a num
     False positive rate (default: 1e-3)
  -b num
     False negative rate (default: 0.3)
  -k int
     Maximum number of losses per SNV (default: 1)
  -s int
     Random number generator seed (default: 0)
  -t int
     Number of threads (default: 1)
  -v
     Verbose output

An example execution:

$ ./kDPFC ../data/CRC/CRC1.input -a 0.0152 -b 0.0789 > CRC1.A
Number of fixed characters = 0
Number of fixed taxa = 0
Base log likelihood = 0
Step 1 -- elapsed time 0.020782 s
Step 1 -- number of constraints: 150
Step 1 -- number of active variables: 217
...

Solution visualization (visualize)

The visualize executable generates a tree in DOT format.

Usage:
  ./visualize [--help|-h|-help] [-T] [-c str] [-t str] input
Where:
  input
     Input file
  --help|-h|-help
     Print a short help message
  -T
     Use tree instead of matrix
  -c str
     Character labels
  -t str
     Taxon labels

An example execution:

$ ./visualize CRC1.A -c ../data/CRC/CRC1_SNV.labels -t ../data/CRC/CRC1_cell.labels > CRC1.dot
$ dot -Tpng CRC1.dot -o CRC1.png

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Single-cell Phylogeny Reconstruction

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