a genomescale differential loop finder
Project description
hic3defdr
A genomescale differential loop finder.
For the latest source, discussion, etc, please visit the Bitbucket repository at https://bitbucket.org/creminslab/hic3defdr
Installation
We require Python 2.7.11+ or 3.6+ and the dependencies listed in setup.py
.
A typical quick install process should be:
$ virtualenv venv
$ source venv/bin/activate
(venv)$ pip install hic3defdr
A typical devmode install process should be:
$ git clone https://bitbucket.org/creminslab/hic3defdr.git
$ cd hic3defdr
$ virtualenv venv
$ source venv/bin/activate
(venv)$ pip install e .
If installation succeeded then hic3defdr.HiC3DeFDR
should be importable from
an interactive shell started in some other directory:
(venv)$ cd <some other directory>
(venv)$ python
>>> from hic3defdr import HiC3DeFDR
Optional dependencies
Evaluating simulations requires scikitlearn:
(venv)$ pip install scikitlearn
To display progress bars during selected steps of the analysis, install tqdm:
(venv)$ pip install tqdm
Basic walkthrough
Before we start, we'll seed numpy's random number generator for reproducibility:
>>> import numpy as np
>>> np.random.seed(42)
To analyze the ES_1, ES_3, NPC_1, and NPC_2 reps of the dataset dataset from Bonev et al. 2017 with default parameters, we would first describe the dataset in terms of replicate names, chromosome names, and a design matrix. We will just analyze chromosomes 18 and 19 here for illustrative purposes.
>>> import pandas as pd
>>>
>>> repnames = ['ES_1', 'ES_3', 'NPC_1', 'NPC_2']
>>> #chroms = ['chr%i' % i for i in range(1, 20)] + ['chrX']
>>> chroms = ['chr18', 'chr19']
>>> design = pd.DataFrame({'ES': [1, 1, 0, 0], 'NPC': [0, 0, 1, 1]},
... dtype=bool, index=repnames)
If you're following along, you can download the data like this:
$ python m hic3defdr.util.demo_data
or from inside an interactive shell:
>>> from hic3defdr.util.demo_data import ensure_demo_data
>>> ensure_demo_data()
The data will be downloaded to a folder called hic3defdrdemodata
under your
home directory.
The required input files consist of:
 upper triangular, raw contact matrices in
scipy.sparse
NPZ format,  bias vectors in plaintext
np.savetxt()
format, and  loop cluster files in sparse JSON format (see below for more details), specifying the locations of loops present in each condition
TODO: explain how to import data from common HiC analysis tools into this format
We would next describe the location of the input data files and use those to
construct a HiC3DeFDR
object:
>>> import os.path
>>> from hic3defdr import HiC3DeFDR
>>>
>>> base_path = os.path.expanduser('~/hic3defdrdemodata/')
>>> h = HiC3DeFDR(
... raw_npz_patterns=[base_path + '<rep>/<chrom>_raw.npz'.replace('<rep>', repname) for repname in repnames],
... bias_patterns=[base_path + '<rep>/<chrom>_kr.bias'.replace('<rep>', repname) for repname in repnames],
... chroms=chroms,
... design=design,
... outdir='output',
... loop_patterns={c: base_path + 'clusters/%s_<chrom>_clusters.json' % c for c in ['ES', 'NPC']},
... res=10000
... )
creating directory output
This object saves itself to disk, so it can be reloaded at any time:
>>> h = HiC3DeFDR.load('output')
To run the analysis for all chromosomes through qvalues, run:
>>> h.run_to_qvalues()
To threshold, cluster, and classify the significantly differential loops, and collect all the results into a single TSV output file, run:
>>> h.collect()
The output file will be written to output/results_0.01_3.tsv
, where "output"
refers to the outdir
we passed when constructing the HiC3DeFDR
object,
"0.01" refers to the default FDR of 1%, and "3" refers to the default cluster
size threshold of 3.
>>> import pandas as pd
>>> pd.read_csv('output/results_0.05_3.tsv', sep='\t', index_col=0).head()
us_chrom ... classification
loop_id ...
chr18:34800003500000_chr18:46800004710000 chr18 ... constitutive
chr18:34900003510000_chr18:37900003810000 chr18 ... ES
chr18:34900003510000_chr18:39700003990000 chr18 ... constitutive
chr18:34900003510000_chr18:41700004200000 chr18 ... constitutive
chr18:34900003520000_chr18:41200004150000 chr18 ... constitutive
<BLANKLINE>
[5 rows x 9 columns]
See the section "TSV output format" below for more details about the output format.
Stepbystep walkthrough
Calling h.run_to_qvalues()
runs the four main steps of the analysis in
sequence. These four steps are described in further detail below. Any kwargs
passed to h.run_to_qvalues()
will be passed along to the appropriate step; see
help(HiC3DeFDR.run_to_qvalues)
for details.
Step 1: Preparing input data
The function call h.prepare_data()
prepares the input raw contact matrices and
bias vectors specified by h.raw_npz_patterns
and h.bias_patterns
for all
chromosomes specified in h.chroms
, performs library size normalization, and
determines what points should be considered for dispersion estimation. This
creates intermediate files in the output directory h.outdir
that represent the
raw and scaled values, as well as the estimated size factors, and a boolean
vector disp_idx
indicating which points will be used for dispersion
estimation. If loop_patterns
was passed to the constructor, an additional
boolean vector loop_idx
is created to mark which points that pass disp_idx
lie within looping interactions specified by h.loop_patterns
. The raw and
scaled data are stored in a rectangular matrix format where each row is a pixel
of the contact matrix and each column is a replicate. If the size factors are
estimated as a function of distance, the estimated size factors are also stored
in this format. Two separate vectors called row
and col
are used to store
the row and column index of the pixel represented by each row of the rectangular
matrices. Together, the row
and col
vectors plus any of the rectangular
matrices represent a generalization of a COO format sparse matrix to multiple
replicates (in the standard COO format the row
and col
vectors are
complemented by a single value
vector).
The size factors can be estimated with a variety of methods defined in the
hic3defdr.scaling
module. The method to use is specified by the norm
kwarg
passed to h.prepare_data()
. Some of these methods estimate size factors as a
function of interaction distance, instead of simply estimating one size factor
for each replicate as is common in RNAseq differential expression analysis.
When these methods are used, the number of bins to use when binning distances
for distancebased estimation of the size factors can be specified with the
n_bins
kwarg. The defaults for this function use the conditional median of
ratios approach (hic3defdr.scaling.conditional_mor
) and an
automaticallyselected number of bins.
Step 2: Estimating dispersions
The function call h.estimate_disp()
estimates the dispersion parameters at
each distance scale in the data and fits a lowess curve through the graph of
distance versus dispersion to obtain final smoothed dispersion estimates for
each pixel.
The estimator
kwarg on h.estimate_disp()
specifies which dispersion
estimation method to use, out of a selection of options defined in the
hic3defdr.dispersion
module. The default is to use quantileadjusted
conditional maximum likelihood (qCML).
Step 3: Likelihood ratio test
The function call h.lrt()
performs a likelihood ratio test (LRT) for each
pixel. This LRT compares a null model of no differential expression (fitting one
true mean parameter shared by all replicates irrespective of condition) to an
alternative model in which the two conditions have different true mean
parameters.
Step 4: False discovery rate (FDR) control
The function call h.bh()
performs BenjaminiHochberg FDR correction on the
pvalues called via the LRT in the previous step, considering only a subset of
pixels that are involved in looping interactions (as specified by
h.loop_patterns
; if loop_patterns
was not passed to the constructor then all
pixels are included in the BHFDR correction). This results in final qvalues
for each loop pixel.
Thresholding, clustering, and classification
We can threshold, cluster, classify, and collect the significantly differential loops:
>>> h.collect(fdr=0.05, cluster_size=3)
We can also sweep across FDR and/or cluster size thresholds:
>>> h.collect(fdr=[0.01, 0.05], cluster_size=[3, 4])
The final output file for each combination of thresholding parameters will be
written to <h.outdir>/results_<fdr>_<cluster_size>.tsv
.
This example walkthrough should take less than 5 minutes for the two chromosomes included in the demo data. Run time for a wholegenome analysis will depend on parallelization as discussed in the next section.
Parallelization
The functions run_to_qvalues()
, prepare_data()
, lrt()
, threshold()
,
classify()
, and simulate()
operate in a perchromosome manner. By default,
each chromosome in the dataset will be processed in series. If multiple cores
and sufficient memory are available, you can use the n_threads
kwarg on these
functions to use multiple subprocesses to process multiple chromosomes in
parallel. Pass either a desired number of subprocesses to use, or pass
n_threads=1
to use all available cores. The output logged to stderr will be
truncated to reduce clutter from multiple subprocesses printing to stderr at the
same time. This truncation is controlled by the verbose
kwarg which is
available on some of these parallelized functions.
The function estimate_disp()
also accepts an n_threads
kwarg, using it to
parallelize itself across distance scales.
The function run_to_qvalues()
passes the n_threads
kwarg through to all the
steps it calls.
Intermediates and final output files
All intermediates used in the computation will be saved to the disk inside the
outdir
folder as <intermediate>_<chrom>.npy
(most intermediates),
<intermediate>_<chrom>.json
/<intermediate>_<chrom>.tsv
(thresholded or
classified clusters).
Two intermediates are not generated per chromosome. These are
disp_fn_<c>.pickle
(dispersion function estimated across all chromosomes for
condition <c>
) and results_<f>_<s>.tsv
(final combined results from all
chromosomes).
Step  Intermediate  Shape  Description 

prepare_data() 
row 
(n_pixels,) 
Toplevel row index 
prepare_data() 
col 
(n_pixels,) 
Toplevel column index 
prepare_data() 
bias 
(n_bins, n_reps) 
Bias vectors 
prepare_data() 
raw 
(n_pixels, n_reps) 
Raw count values 
prepare_data() 
size_factors 
(n_reps,) or (n_pixels, n_reps) 
Size factors 
prepare_data() 
scaled 
(n_pixels, n_reps) 
Normalized count values 
prepare_data() 
disp_idx 
(n_pixels,) 
Marks pixels for which dispersion is fitted 
prepare_data() 
loop_idx 
(disp_idx.sum(),) 
Marks pixels which lie in loops 
estimate_disp() 
cov_per_bin 
(n_bins, n_conds) 
Average mean count or distance in each bin 
estimate_disp() 
disp_per_bin 
(n_bins, n_conds) 
Pooled dispersion estimates in each bin 
estimate_disp() 
disp_fn_<c> 
pickled function  Fitted dispersion function 
estimate_disp() 
disp 
(disp_idx.sum(), n_conds) 
Smoothed dispersion estimates 
lrt() 
mu_hat_null 
(disp_idx.sum(),) 
Null model mean parameters 
lrt() 
mu_hat_alt 
(disp_idx.sum(), n_conds) 
Alternative model mean parameters 
lrt() 
llr 
(disp_idx.sum(),) 
Loglikelihood ratio 
lrt() 
pvalues 
(disp_idx.sum(),) 
LRTbased pvalue 
bh() 
qvalues 
(loop_idx.sum(),) 
BHcorrected qvalues 
threshold() 
sig_<f>_<s> 
JSON/TSV  Significantly differential clusters 
threshold() 
insig_<f>_<s> 
JSON/TSV  Constitutive clusters 
classify() 
<c>_<f>_<s> 
JSON/TSV  Classified differential clusters 
collect() 
results_<f>_<s> 
TSV  Final results table 
The table uses these abbreviations to refer to variable parts of certain intermediate names:
<f>
: FDR threshold<s>
: cluster size threshold<c>
: condition/class label
Sparse JSON cluster format
This is the format used both for supplying preidentified, percondition loop clusters as input to HiC3DeFDR as well as the format in which differential and constitutive interaction clusters are reported as output.
The format describes the clusters on each chromosome in a separate JSON file. This JSON file contains a single JSON object, which is a list of list of list of integers. The inner lists are all of length 2 and represent specific pixels of the heatmap for that chromosome in terms of there row and column coordinates in zeroindexed bin units. The outer middle lists can be of any length and represent groups of pixels that belong to the same cluster. The length of the outer list corresponds to the number of clusters on that chromosome.
These clusters can be loaded into and written from the corresponding plain
Python objects using hic3defdr.clusters.load_clusters()
and
hic3defdr.clusters.save_clusters()
, respectively. The plain Python objects can
be converted to and from scipy sparse matrix objects using
hic3defdr.clusters.clusters_to_coo()
and
hic3defdr.clusters.convert_cluster_array_to_sparse()
, respectively.
TSV output format
The final TSV output file results_<f>_<s>.tsv
has as its first column a
loop_id
, a string of the form
<us_chrom>:<us_start><us_end>_<ds_chrom>:<ds_start><ds_end>
specifying a
rectangle that surrounds the cluster of pixels that make up the loop. The next
six columns are the six individual pieces of this loop_id
. This is followed
by:
cluster_size
: the number of pixels in the clustercluster
: a list of the exact (row, col) indices of the pixels in the clusterclassification
: this will be "constitutive" if the loop is not differential, or the name of the condition the loop is specific to (i.e., strongest in) if it is differential
Visualizations
The HiC3DeFDR
object can be used to draw visualizations of the analysis.
The visualization functions are wrapped with the @plotter decorator
and therefore all support the convenience kwargs provided by that decorator
(such as outfile
).
Distance dependence curves before and after scaling
>>> _ = h.plot_dd_curves('chr18', outfile='images/dd.png')
Simple heatmap plotting
>>> _ = h.plot_heatmap('chr18', slice(1000, 1100), slice(1000, 1100), rep='ES_1',
... outfile='images/heatmap.png')
By default, this plots data at the "scaled" stage (normalized for bias and
sequencing depth differences), but you can plot any stage of the data by passing
a stage
kwarg.
Conditionaverage heatmap plotting
To plot a withincondition average heatmap, pass a stage
name with a '_mean'
suffix appended and cond
to specify the condition to average within:
>>> _ = h.plot_heatmap('chr18', slice(1000, 1100), slice(1000, 1100),
... stage='scaled_mean', cond='ES',
... outfile='images/heatmap_mean.png')
Loop zoomin heatmap plotting
We can combine h.plot_heatmap()
with the load_clusters()
and
cluster_to_slices()
utility functions in hic3defdr.util.clusters
to plot
zoomins around specific loops:
>>> from hic3defdr.util.clusters import load_clusters, cluster_to_slices
>>> chrom = 'chr18'
>>> clusters = load_clusters(h.loop_patterns['ES'].replace('<chrom>', chrom))
>>> slices = cluster_to_slices(clusters[23])
>>> _ = h.plot_heatmap(chrom, *slices, rep='ES_1', outfile='images/zoomin.png')
Perpixel significance plotting
We can pass stage='qvalues'
to h.plot_heatmap()
to draw heatmaps showing the
significance of each pixel:
>>> _ = h.plot_heatmap('chr18', slice(1310, 1370), slice(1310, 1370),
... stage='qvalues', cmap='bwr_r', vmin=0.099, vmax=0.101,
... outfile='images/heatmap_sig.png')
By passing cmap='bwr_r'
we ensure that significant, low qvalue pixels will be
red while insignificant, high qvalue pixels will be blue. By passing
vmin=0.099, vmax=0.101
, we ensure that the colorbar is focused on a narrow
range around an FDR threshold of 10%, allowing us to more easily tell the
difference between significant and insignificant pixels.
Correlation matrices
>>> _ = h.plot_correlation_matrix(outfile='images/correlation.png')
Dispersion fitting
>>> _ = h.plot_dispersion_fit('ES', outfile='images/ddr.png')
It's possible to use the the onedimensional distance dependence curve to
convert distances to means. Doing so allows plotting the yaxis in terms of
variance. You can do this by passing yaxis='var'
:
>>> _ = h.plot_dispersion_fit('ES', yaxis='var', outfile='images/dvr.png')
Using the same trick, you can plot the xaxis in terms of mean by passing
xaxis='mean'
:
>>> _ = h.plot_dispersion_fit('ES', xaxis='mean', yaxis='var',
... outfile='images/mvr.png')
At low mean and high distance, the distance dependence curve flattens out and the data become more noisy, making this conversion unreliable.
It's also possible to show the dispersion fitted at just one distance scale, overlaying the sample mean and sample variance across replicates for each pixel as a blue hexbin plot:
>>> _ = h.plot_dispersion_fit('ES', distance=25, hexbin=True, xaxis='mean',
... yaxis='var', logx=True, logy=True,
... outfile='images/mvr_25.png')
If dispersion was fitted against distance rather than mean, pass xaxis='dist'
to plot dispersion/variance versus distance.
Comparing dispersion fits
It's possible to compare different dispersion fits using the function
compare_disp_fits()
as shown here:
>>> from hic3defdr import compare_disp_fits
>>>
>>> _ = compare_disp_fits(
... [h.load_disp_fn(cond) for cond in h.design.columns],
... h.design.columns,
... max_dist=100,
... outfile='images/disp_comparison.png'
... )
Pvalue distribution
>>> _ = h.plot_pvalue_distribution(outfile='images/pvalue_dist.png')
By default, this plots the pvalue distribution over all pixels for which
dispersion was estimated. To plot the pvalue distribution only over points in
loops, pass idx='loop'
.
Qvalue distribution
>>> _ = h.plot_qvalue_distribution(outfile='images/qvalue_dist.png')
MA plot
>>> _ = h.plot_ma(outfile='images/ma.png')
Pixel detail grid
>>> _ = h.plot_grid('chr18', 2218, 2236, 20, outfile='images/grid.png')
The upper right heatmaps show the balanced and scaled values in each replicate, with each condition on its own row.
The upper left heatmaps show the alternative model mean parameter estimates for each condition. Significantly differential clusters are purple while constitutive ones are gray.
The lower left heatmap shows the qvalues. Significantly differential clusters are orange while constitutive ones are gray.
The stripplots in the lower left show details information about the specific
pixel in the center of the heatmaps (in this example (2218, 2236)
). The dots
show the values at that pixel for each replicate in normalized and raw space,
repsectively. The solid and dashed lines represent the mean parameters under the
alt and null models, repsectively.
Green points in the heatmaps represent points that have been filtered out. For the perreplicate heatmaps in the upper right of the grid, the only filters applied are the zero filter, bias filter, and distance filter. For the alt model mean heatmaps in the upper left, this additionally includes the dispersion filter. For the qvalue heatmap in the lower left, it additionally includes the loop filter if loop locations were supplied.
Interactive thresholding
In a Jupyter notebook environment with ipywidgets
installed, you can play with
thresholds on a liveupdating plot by running:
%matplotlib notebook
from ipywidgets import interact
from hic3defdr import HiC3DeFDR
h = HiC3DeFDR.load('output')
_, _, outline_clusters = h.plot_grid('chr18', 2218, 2236, 50)
_ = interact(outline_clusters, fdr=[0.01, 0.05, 0.1, 0.2],
cluster_size=[3, 4])
Simulation
After the estimate_disp()
step has been run, a HiC3DeFDR object can be used to
generate simulations of differential looping.
Generating simulations
To create an ESbased simulation over all chromosomes listed in h.chroms
, we
run
>>> from hic3defdr import HiC3DeFDR
>>>
>>> h = HiC3DeFDR.load('output')
>>> h.simulate('ES')
If we passed trend='dist'
to h.estimate_disp()
, we need to pass it to
h.simulate()
as well to ensure that the simulation function knows to treat the
previouslyfitted dispersion function as a function of distance.
This takes the mean of the real scaled data across the ES replicates and
perturbs the loops specified in h.loop_patterns['ES']
up or down at random to
generate two new conditions called "A" and "B". The scaled mean matrices for
these conditions are then biased and scaled by the bias vectors and size factors
taken from the real experimental replicates, and the ES dispersion function
fitted to the real ES data is applied to the biased and scaled means to obtain
dispersion values. These means and dispersions are used to draw an NB random
variable for each pixel of each simulated replicate. The number of replicates in
each of the simulated conditions "A" and "B" will match the design of the real
analysis.
The simulated raw contact matrices will be written to disk in CSR format as
<cond><rep>_<chrom>_raw.npz
where <cond>
is "A" or "B" and <rep>
is the
rep number within the condition. The design matrix will also be written to disk
as design.csv
.
The true labels used to perturb the loops will also be written to disk as
labels_<chrom>.txt
. This file contains as many lines as there are clusters in
h.loop_patterns['ES']
, with the i
th line providing the label for the i
th
cluster. This file can be loaded with np.loadtxt(..., dtype='S7')
.
Evaluating simulations
After generating simulated data, HiC3DeFDR can be run on the simulated data. Then, the true labels can be used to evaluate the performance of HiC3DeFDR on the simulated data.
Evaluation of simulated data requires scikitlearn. To install this package, run
(venv)$ pip install scikitlearn
In order to run HiC3DeFDR on the simulated data, we first need to balance the
simulated raw contact matrices to obtain bias vectors for each simulated
replicate and chromosome. We will assume are saved next to the raw contact
matrices and named <rep>_<chrom>_kr.bias
. One example of how this can be done
is shown in the following script:
>>> import sys
>>>
>>> import numpy as np
>>> import scipy.sparse as sparse
>>>
>>> from hic3defdr.util.filtering import filter_sparse_rows_count
>>> from hic3defdr.util.balancing import kr_balance
>>> from hic3defdr.util.printing import eprint
>>>
>>>
>>> infile_pattern = 'sim/<rep>_<chrom>_raw.npz'
>>> repnames = ['A1', 'A2', 'B1', 'B2']
>>> chroms = ['chr18', 'chr19']
>>>
>>> for repname in repnames:
... for chrom in chroms:
... eprint('balancing rep %s chrom %s' % (repname, chrom))
... infile = infile_pattern.replace('<rep>', repname)\
... .replace('<chrom>', chrom)
... outfile = infile.replace('_raw.npz', '_kr.bias')
... _, bias, _ = kr_balance(
... filter_sparse_rows_count(sparse.load_npz(infile)), fl=0)
... np.savetxt(outfile, bias)
Next, we create a new HiC3DeFDR object to analyze the simulated data and run the analysis through to qvalues:
>>> import os.path
>>> from hic3defdr import HiC3DeFDR
>>>
>>> repnames = ['A1', 'A2', 'B1', 'B2']
>>> chroms = ['chr18', 'chr19']
>>> sim_path = 'sim/'
>>> base_path = os.path.expanduser('~/hic3defdrdemodata/')
>>> h_sim = HiC3DeFDR(
... raw_npz_patterns=[sim_path + '<rep>_<chrom>_raw.npz'.replace('<rep>', repname) for repname in repnames],
... bias_patterns=[sim_path + '<rep>_<chrom>_kr.bias'.replace('<rep>', repname) for repname in repnames],
... chroms=chroms,
... design=sim_path + 'design.csv',
... outdir='outputsim',
... loop_patterns={'ES': base_path + 'clusters/ES_<chrom>_clusters.json'}
... )
creating directory outputsim
>>> h_sim.run_to_qvalues()
Next, we can evaluate the simulation against the clusters in
h_sim.loop_patterns['ES']
with true labels from sim/labels_<chrom>.txt
:
>>> h_sim.evaluate('ES', 'sim/labels_<chrom>.txt')
This writes a file in h_sim
's output directory called eval.npz
. This file
can be loaded with np.load()
and has four keys whose values are all one
dimensional vectors:
'thresh'
: the thresholds (in1  qvalue
space) which make up the convex edge of the ROC curve; all other vectors are parallel to this one'fdr'
: the observed false discovery rate at each threshold'tpr'
: the observed true positive rate at each threshold'fpr'
: the observed false positive rate at each threshold
eval.npz
files (possibly across many runs) can be visualized as ROC curves and
FDR control curves by running:
>>> import numpy as np
>>> from hic3defdr import plot_roc, plot_fdr
>>>
>>> _ = plot_roc([np.load('outputsim/eval.npz')], ['hic3defdr'], outfile='images/roc.png')
>>> _ = plot_fdr([np.load('outputsim/eval.npz')], ['hic3defdr'], outfile='images/fdr.png')
Multiple eval.npz
files can be compared in the same plot by simply adding
elements to the lists in these function calls.
The ROC plot shows FPR versus TPR, with the gray diagonal line representing the performance of random guessing. The AUROC for each curve is shown in the legend. If only one curve is plotted, selected thresholds (in units of FDR threshold) are annotated with black arrows.
The FDR control plot shows the observed FDR as a function of the FDR threshold. Points below the gray diagonal line represent points at which FDR is successfully controlled.
As an added bonus, it's also possible to evaluate the performance on specific
subsets of distance scales by using the min_dist
and max_dist
kwargs on
HiC3DeFDR.evaluate()
as illustrated below:
>>> dist_bins = [
... ('short', (None, 15)), # distances in bin units
... ('mid', (16, 30)),
... ('long', (31, None))
... ]
>>> for _, (min_dist, max_dist) in dist_bins:
... h_sim.evaluate('ES', 'sim/labels_<chrom>.txt', min_dist=min_dist,
... max_dist=max_dist)
>>> _ = plot_roc([np.load('outputsim/eval_%s_%s.npz' % (min_dist, max_dist))
... for _, (min_dist, max_dist) in dist_bins],
... [label for label, _ in dist_bins],
... outfile='images/roc_by_dist.png')
>>> _ = plot_fdr([np.load('outputsim/eval_%s_%s.npz' % (min_dist, max_dist))
... for _, (min_dist, max_dist) in dist_bins],
... [label for label, _ in dist_bins],
... outfile='images/fdr_by_dist.png')
It's also possible to compare the FPR and FNR at the different subsets:
>>> from hic3defdr import plot_fn_vs_fp
>>>
>>> _ = plot_fn_vs_fp([np.load('outputsim/eval_%s_%s.npz' % (min_dist, max_dist))
... for _, (min_dist, max_dist) in dist_bins],
... [label for label, _ in dist_bins], xlabel='distance subset',
... outfile='images/fn_vs_fp.png')
Other visualizations
Distance bias
We can visualize and compare the distance bias of different simulations (the
degree to which low pvalues are enriched or depleted in different distance
scales) using the plot_distance_bias()
function as shown below:
>>> from hic3defdr import plot_distance_bias
>>>
>>> dist_bins = [
... ('short', (None, 15)), # distances in bin units
... ('mid', (16, 30)),
... ('long', (31, None))
... ]
>>> _ = plot_distance_bias([h, h_sim], [b for _, b in dist_bins], labels=['real', 'sim'], outfile='images/distance_bias.png')
Package structure
The hic3defdr
package is layed out in three parts:
hic3defdr.util
: library of reusable functions for performing computations related to differential loop callinghic3defdr.plotting
: library of reusable functions to plotting visualizations related to differential loop callinghic3defdr.analysis
: a module that defines the HiC3DeFDR class, which provides an implementation of stitching together all the computational steps and visualizations in an easytouse way
The HiC3DeFDR class includes many methods, so to keep things organized these
methods are defined in four separate mixin classes which are combined to form
the full HiC3DeFDR class in hic3defdr/analysis/constructor.py
:
hic3defdr.analysis.core.CoreHiC3DeFDR
hic3defdr.analysis.analysis.AnalyzingHiC3DeFDR
hic3defdr.analysis.simulation.SimulatingHiC3DeFDR
hic3defdr.analysis.plotting.PlottingHiC3DeFDR
We recommend that most users simply import the HiC3DeFDR class and interact with
this package through that interface, but the functions defined in
hic3efdr.util
and hic3defdr.plotting
may also be useful to some users and
are designed to be somewhat reusable.
The complete layout of the package is summarized below:
hic3defdr/ # package root
â”œâ”€â”€ _version.py # version configuration
â”œâ”€â”€ analysis/ # HiC3DeFDR class and alternatives
â”‚ â”œâ”€â”€ alternatives.py # defines alternative analysis models
â”‚ â”œâ”€â”€ analysis.py # HiC3DeFDR's pipeline methods
â”‚ â”œâ”€â”€ constructor.py # HiC3DeFDR's class definition and constructor
â”‚ â”œâ”€â”€ core.py # HiC3DeFDR's core save/load methods
â”‚ â”œâ”€â”€ plotting.py # HiC3DeFDR's plotting methods
â”‚ â””â”€â”€ simulation.py # HiC3DeFDR's simulation/evaluation methods
â”œâ”€â”€ plotting/ # library of plotting functions
â”‚ â”œâ”€â”€ dispersion.py # dispersion/variance fit visualizations
â”‚ â”œâ”€â”€ distance_bias.py # distance bias comparison barplots
â”‚ â”œâ”€â”€ distance_dependence.py # distance dependence curve comparison
â”‚ â”œâ”€â”€ fdr.py # FDR control curve plotting
â”‚ â”œâ”€â”€ fn_vs_fp.py # FN vs FP tradeoff barplots
â”‚ â”œâ”€â”€ grid.py # "pixel detail grid" combination visualization
â”‚ â”œâ”€â”€ heatmap.py # simple contact matrix heatmap plotting
â”‚ â”œâ”€â”€ histograms.py # pvalue/qvalue histograms
â”‚ â”œâ”€â”€ ma.py # MA plots
â”‚ â””â”€â”€ roc.py # ROC curve plots
â””â”€â”€ util/ # library of utility functions
â”œâ”€â”€ binning.py # creating groups of points
â”œâ”€â”€ balancing.py # KR matrix balancing
â”œâ”€â”€ banded_matrix.py # BandedMatrix class (used for filtering)
â”œâ”€â”€ classification.py # classifying differential loop pixels
â”œâ”€â”€ cluster_table.py # creating tables summarizing cluster info
â”œâ”€â”€ clusters.py # interacting with called loop clusters
â”œâ”€â”€ demo_data.py # utilities for downloading the demo dataset
â”œâ”€â”€ dispersion.py # estimating dispersions in NB data
â”œâ”€â”€ evaluation.py # evaluating results of simulations
â”œâ”€â”€ filtering.py # filtering (applied before balancing)
â”œâ”€â”€ lowess.py # lowess fitting
â”œâ”€â”€ lrt.py # NB likelihood ratio testing
â”œâ”€â”€ matrices.py # interacting with sparse matrices
â”œâ”€â”€ parallelization.py # parallelizing work across cores
â”œâ”€â”€ printing.py # printing updates and info to the console
â”œâ”€â”€ progress.py # showing progress bars
â”œâ”€â”€ scaled_nb.py # dealing with scaling factors in NB
â”œâ”€â”€ scaling.py # scaling reps to account for sequencing depth
â”œâ”€â”€ simulation.py # simulating pseudoreplicates
â””â”€â”€ thresholding.py # thresholding differential pixels/clusters
Additional options
Additional options are exposed as kwargs on the functions in this library. Use
help(<function>)
to get detailed information about the options available for
any function and what these options may be used for.
Testing
We run our tests with tox. To execute tests,
install tox (pip install tox
) and then run tox
to run all tests or
tox e <testenv>
to run a specific test environment. See tox.ini
for the
full specification of all test environments.
Project details
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