In [1]:
import os
import util
from tomtom import match_motifs_to_database
import viz_sequence
import numpy as np
import pandas as pd
import sklearn.cluster
import scipy.cluster.hierarchy
import matplotlib.pyplot as plt
import matplotlib.font_manager as font_manager
import vdom.helpers as vdomh
from IPython.display import display
import tqdm
tqdm.tqdm_notebook()
/users/amtseng/miniconda3/envs/tfmodisco-mini/lib/python3.7/site-packages/ipykernel_launcher.py:14: TqdmDeprecationWarning: This function will be removed in tqdm==5.0.0
Please use `tqdm.notebook.tqdm` instead of `tqdm.tqdm_notebook`
  
Out[1]:
0it [00:00, ?it/s]
In [2]:
# Plotting defaults
font_manager.fontManager.ttflist.extend(
    font_manager.createFontList(
        font_manager.findSystemFonts(fontpaths="/users/amtseng/modules/fonts")
    )
)
plot_params = {
    "figure.titlesize": 22,
    "axes.titlesize": 22,
    "axes.labelsize": 20,
    "legend.fontsize": 18,
    "xtick.labelsize": 16,
    "ytick.labelsize": 16,
    "font.family": "Roboto",
    "font.weight": "bold"
}
plt.rcParams.update(plot_params)
/users/amtseng/miniconda3/envs/tfmodisco-mini/lib/python3.7/site-packages/ipykernel_launcher.py:4: MatplotlibDeprecationWarning: 
The createFontList function was deprecated in Matplotlib 3.2 and will be removed two minor releases later. Use FontManager.addfont instead.
  after removing the cwd from sys.path.

Define constants and paths

In [3]:
# Define parameters/fetch arguments
preds_path = os.environ["TFM_PRED_PATH"]
shap_scores_path = os.environ["TFM_SHAP_PATH"]
tfm_results_path = os.environ["TFM_TFM_PATH"]
peak_bed_paths = [os.environ["TFM_PEAKS_PATH"]]

print("Predictions path: %s" % preds_path)
print("DeepSHAP scores path: %s" % shap_scores_path)
print("TF-MoDISco results path: %s" % tfm_results_path)
print("Peaks path: %s" % peak_bed_paths[0])
Predictions path: /users/zahoor/TF-Atlas/02-16-2021/predictions/ENCSR000DTO/profile_predictions.h5
DeepSHAP scores path: /users/zahoor/TF-Atlas/02-16-2021/shap/ENCSR000DTO/profile_scores_alex_format.h5
TF-MoDISco results path: /users/zahoor/TF-Atlas/02-16-2021/modisco/ENCSR000DTO/profile/modisco_results.hd5
Peaks path: /users/zahoor/TF-Atlas/data/idr_peaks//ENCFF832INR.bed.gz
In [4]:
# Define constants
input_length, profile_length = 2114, 1000
shap_score_center_size = 400
profile_display_center_size = 400
hyp_score_key = "hyp_scores"
task_index = None

Helper functions

In [5]:
def extract_profiles_and_coords(
    seqlets_arr, one_hot_seqs, hyp_scores, true_profs, pred_profs, pred_coords,
    input_length, profile_length, input_center_cut_size, profile_center_cut_size,
    task_index=None
):
    """
    From the seqlets object of a TF-MoDISco pattern's seqlets and alignments,
    extracts the predicted and observed profiles of the model, as well as the
    set of coordinates for the seqlets.
    Arguments:
        `seqlets_arr`: a TF-MoDISco pattern's seqlets object array (N-array)
        `one_hot_seqs`: an N x R x 4 array of input sequences, where R is
            the cut centered size
        `hyp_scores`: an N x R x 4 array of hypothetical importance scores
        `true_profs`: an N x T x O x 2 array of true profile counts
        `pred_profs`: an N x T x O x 2 array of predicted profile probabilities
        `pred_coords`: an N x 3 object array of coordinates for the input sequence
            underlying the predictions
        `input_length`: length of original input sequences, I
        `profile_length`: length of profile predictions, O
        `input_center_cut_size`: centered cut size of SHAP scores used
        `profile_center_cut_size`: size to cut profiles to when returning them, P
        `task_index`: index of task to focus on for profiles; if None, returns
            profiles for all tasks
    Returns an N x (T or 1) x P x 2 array of true profile counts, an
    N x (T or 1) x P x 2 array of predicted profile probabilities, an N x Q x 4
    array of one-hot seqlet sequences, an N x Q x 4 array of hypothetical seqlet
    importance scores, and an N x 3 object array of seqlet coordinates, where P
    is the profile cut size and Q is the seqlet length. Returned profiles are
    centered at the same center as the seqlets.
    Note that it is important that the seqlet indices match exactly with the indices
    out of the N. This should be the exact sequences in the original SHAP scores.
    """
    true_seqlet_profs, pred_seqlet_profs, seqlet_seqs, seqlet_hyps, seqlet_coords = [], [], [], [], []
    
    def seqlet_coord_to_profile_coord(seqlet_coord):
        return seqlet_coord + ((input_length - input_center_cut_size) // 2) - ((input_length - profile_length) // 2)
    
    def seqlet_coord_to_input_coord(seqlet_coord):
        return seqlet_coord + ((input_length - input_center_cut_size) // 2)
        
    # For each seqlet, fetch the true/predicted profiles
    for seqlet in seqlets_arr:
        coord_index = seqlet.coor.example_idx
        seqlet_start = seqlet.coor.start
        seqlet_end = seqlet.coor.end
        seqlet_rc = seqlet.coor.is_revcomp
        
        # Get indices of profile to cut out
        seqlet_center = (seqlet_start + seqlet_end) // 2
        prof_center = seqlet_coord_to_profile_coord(seqlet_center)
        prof_start = prof_center - (profile_center_cut_size // 2)
        prof_end = prof_start + profile_center_cut_size
        
        if task_index is None or true_profs.shape[1] == 1:
            # Use all tasks if the predictions only have 1 task to begin with
            task_start, task_end = None, None
        else:
            task_start, task_end = task_index, task_index + 1
            
        true_prof = true_profs[coord_index, task_start:task_end, prof_start:prof_end]  # (T or 1) x P x 2
        pred_prof = pred_profs[coord_index, task_start:task_end, prof_start:prof_end]  # (T or 1) x P x 2
        
        true_seqlet_profs.append(true_prof)
        pred_seqlet_profs.append(pred_prof)
        
        # The one-hot-sequences and hypothetical scores are assumed to already by cut/centered,
        # so the indices match the seqlet indices
        if seqlet_rc:
            seqlet_seqs.append(np.flip(one_hot_seqs[coord_index, seqlet_start:seqlet_end], axis=(0, 1)))
            seqlet_hyps.append(np.flip(hyp_scores[coord_index, seqlet_start:seqlet_end], axis=(0, 1)))
        else:
            seqlet_seqs.append(one_hot_seqs[coord_index, seqlet_start:seqlet_end])
            seqlet_hyps.append(hyp_scores[coord_index, seqlet_start:seqlet_end])
            
        # Get the coordinates of the seqlet based on the input coordinates
        inp_start = seqlet_coord_to_input_coord(seqlet_start)
        inp_end = seqlet_coord_to_input_coord(seqlet_end)
        chrom, start, _ = pred_coords[coord_index]
        seqlet_coords.append([chrom, start + inp_start, start + inp_end])
    
    return np.stack(true_seqlet_profs), np.stack(pred_seqlet_profs), np.stack(seqlet_seqs), np.stack(seqlet_hyps), np.array(seqlet_coords, dtype=object)
In [6]:
def plot_profiles(seqlet_true_profs, seqlet_pred_profs, kmeans_clusters=5):
    """
    Plots the given profiles with a heatmap.
    Arguments:
        `seqlet_true_profs`: an N x O x 2 NumPy array of true profiles, either as raw
            counts or probabilities (they will be normalized)
        `seqlet_pred_profs`: an N x O x 2 NumPy array of predicted profiles, either as
            raw counts or probabilities (they will be normalized)
        `kmeans_cluster`: when displaying profile heatmaps, there will be this
            many clusters
    """
    assert len(seqlet_true_profs.shape) == 3
    assert seqlet_true_profs.shape == seqlet_pred_profs.shape
    num_profs, width, _ = seqlet_true_profs.shape

    # First, normalize the profiles along the output profile dimension
    def normalize(arr, axis=0):
        arr_sum = np.sum(arr, axis=axis, keepdims=True)
        arr_sum[arr_sum == 0] = 1  # If 0, keep 0 as the quotient instead of dividing by 0
        return arr / arr_sum
    true_profs_norm = normalize(seqlet_true_profs, axis=1)
    pred_profs_norm = normalize(seqlet_pred_profs, axis=1)

    # Compute the mean profiles across all examples
    true_profs_mean = np.mean(true_profs_norm, axis=0)
    pred_profs_mean = np.mean(pred_profs_norm, axis=0)

    # Perform k-means clustering on the predicted profiles, with the strands pooled
    kmeans_clusters = max(5, num_profs // 50)  # Set number of clusters based on number of profiles, with minimum
    kmeans = sklearn.cluster.KMeans(n_clusters=kmeans_clusters)
    cluster_assignments = kmeans.fit_predict(
        np.reshape(pred_profs_norm, (pred_profs_norm.shape[0], -1))
    )

    # Perform hierarchical clustering on the cluster centers to determine optimal ordering
    kmeans_centers = kmeans.cluster_centers_
    cluster_order = scipy.cluster.hierarchy.leaves_list(
        scipy.cluster.hierarchy.optimal_leaf_ordering(
            scipy.cluster.hierarchy.linkage(kmeans_centers, method="centroid"), kmeans_centers
        )
    )

    # Order the profiles so that the cluster assignments follow the optimal ordering
    cluster_inds = []
    for cluster_id in cluster_order:
        cluster_inds.append(np.where(cluster_assignments == cluster_id)[0])
    cluster_inds = np.concatenate(cluster_inds)

    # Compute a matrix of profiles, normalized to the maximum height, ordered by clusters
    def make_profile_matrix(flat_profs, order_inds):
        matrix = flat_profs[order_inds]
        maxes = np.max(matrix, axis=1, keepdims=True)
        maxes[maxes == 0] = 1  # If 0, keep 0 as the quotient instead of dividing by 0
        return matrix / maxes
    true_matrix = make_profile_matrix(true_profs_norm, cluster_inds)
    pred_matrix = make_profile_matrix(pred_profs_norm, cluster_inds)

    # Create a figure with the right dimensions
    mean_height = 4
    heatmap_height = min(num_profs * 0.004, 8)
    fig_height = mean_height + (2 * heatmap_height)
    fig, ax = plt.subplots(
        3, 2, figsize=(16, fig_height), sharex=True,
        gridspec_kw={
            "width_ratios": [1, 1],
            "height_ratios": [mean_height / fig_height, heatmap_height / fig_height, heatmap_height / fig_height]
        }
    )

    # Plot the average predictions
    ax[0, 0].plot(true_profs_mean[:, 0], color="darkslateblue")
    ax[0, 0].plot(-true_profs_mean[:, 1], color="darkorange")
    ax[0, 1].plot(pred_profs_mean[:, 0], color="darkslateblue")
    ax[0, 1].plot(-pred_profs_mean[:, 1], color="darkorange")

    # Set axes on average predictions
    max_mean_val = max(np.max(true_profs_mean), np.max(pred_profs_mean))
    mean_ylim = max_mean_val * 1.05  # Make 5% higher
    ax[0, 0].set_title("True profiles")
    ax[0, 0].set_ylabel("Average probability")
    ax[0, 1].set_title("Predicted profiles")
    for j in (0, 1):
        ax[0, j].set_ylim(-mean_ylim, mean_ylim)
        ax[0, j].label_outer()

    # Plot the heatmaps
    ax[1, 0].imshow(true_matrix[:, :, 0], interpolation="nearest", aspect="auto", cmap="Blues")
    ax[1, 1].imshow(pred_matrix[:, :, 0], interpolation="nearest", aspect="auto", cmap="Blues")
    ax[2, 0].imshow(true_matrix[:, :, 1], interpolation="nearest", aspect="auto", cmap="Oranges")
    ax[2, 1].imshow(pred_matrix[:, :, 1], interpolation="nearest", aspect="auto", cmap="Oranges")

    # Set axes on heatmaps
    for i in (1, 2):
        for j in (0, 1):
            ax[i, j].set_yticks([])
            ax[i, j].set_yticklabels([])
            ax[i, j].label_outer()
    width = true_matrix.shape[1]
    delta = 100
    num_deltas = (width // 2) // delta
    labels = list(range(max(-width // 2, -num_deltas * delta), min(width // 2, num_deltas * delta) + 1, delta))
    tick_locs = [label + max(width // 2, num_deltas * delta) for label in labels]
    for j in (0, 1):
        ax[2, j].set_xticks(tick_locs)
        ax[2, j].set_xticklabels(labels)
        ax[2, j].set_xlabel("Distance from peak summit (bp)")

    fig.tight_layout()
    plt.show()
In [7]:
def get_summit_distances(coords, peak_table):
    """
    Given a set of coordinates, computes the distance of the center of each
    coordinate to the nearest summit.
    Arguments:
        `coords`: an N x 3 object array of coordinates
        `peak_table`: a 6-column table of peak data, as imported by
            `import_peak_table`
    Returns and N-array of integers, which is the distance of each coordinate
    midpoint to the nearest coordinate.
    """
    chroms = coords[:, 0]
    midpoints = (coords[:, 1] + coords[:, 2]) // 2
    dists = []
    for i in range(len(coords)):
        chrom = chroms[i]
        midpoint = midpoints[i]
        rows = peak_table[peak_table["chrom"] == chrom]
        dist_arr = (midpoint - rows["summit"]).values
        min_dist = dist_arr[np.argmin(np.abs(dist_arr))]
        dists.append(min_dist)
    return np.array(dists)
In [8]:
def plot_summit_dists(summit_dists):
    """
    Plots the distribution of seqlet distances to summits.
    Arguments:
        `summit_dists`: the array of distances as returned by
            `get_summit_distances`
    """
    plt.figure(figsize=(8, 6))
    num_bins = max(len(summit_dists) // 30, 20)
    plt.hist(summit_dists, bins=num_bins, color="purple")
    plt.title("Histogram of distance of seqlets to peak summits")
    plt.xlabel("Signed distance from seqlet center to nearest peak summit (bp)")
    plt.show()

Import SHAP scores, profile predictions, and TF-MoDISco results

In [9]:
# Import SHAP coordinates and one-hot sequences
hyp_scores, _, one_hot_seqs, shap_coords = util.import_shap_scores(shap_scores_path, hyp_score_key, center_cut_size=shap_score_center_size, remove_non_acgt=False)
# This cuts the sequences/scores off just as how TF-MoDISco saw them, but the coordinates are uncut
Importing SHAP scores: 100%|██████████| 53/53 [00:09<00:00,  5.56it/s]
In [10]:
# Import the set of all profiles and their coordinates
true_profs, pred_profs, all_pred_coords = util.import_profiles(preds_path)

In [11]:
# Import the set of peaks
peak_table = util.import_peak_table(peak_bed_paths)
In [12]:
# Subset the predicted profiles/coordinates to the task-specific SHAP coordinates/scores
shap_coords_table = pd.DataFrame(shap_coords, columns=["chrom", "start", "end"])
pred_coords_table = pd.DataFrame(all_pred_coords, columns=["chrom", "start", "end"])

subset_inds = pred_coords_table.reset_index().drop_duplicates(["chrom", "start", "end"]).merge(
    shap_coords_table.reset_index(), on=["chrom", "start", "end"]
).sort_values("index_y")["index_x"].values

true_profs = true_profs[subset_inds]
pred_profs = pred_profs[subset_inds]
pred_coords = all_pred_coords[subset_inds]

# Make sure the coordinates all match
assert np.all(pred_coords == shap_coords)
In [13]:
# Import the TF-MoDISco results object
tfm_obj = util.import_tfmodisco_results(tfm_results_path, hyp_scores, one_hot_seqs, shap_score_center_size)

Plot some SHAP score tracks

Plot the central region of some randomly selected actual importance scores

In [14]:
for index in np.random.choice(hyp_scores.shape[0], size=5, replace=False):
    viz_sequence.plot_weights((hyp_scores[index] * one_hot_seqs[index])[100:300], subticks_frequency=100)

Plot TF-MoDISco results

Plot all motifs by metacluster

In [15]:
motif_pfms, motif_hcwms, motif_cwms = [], [], []  # Save the trimmed PFMs, hCWMs, and CWMs
motif_pfms_short = []  # PFMs that are even more trimmed (for TOMTOM)
num_seqlets = []  # Number of seqlets for each motif
motif_seqlets = []  # Save seqlets of each motif
metaclusters = tfm_obj.metacluster_idx_to_submetacluster_results
num_metaclusters = len(metaclusters.keys())
for metacluster_i, metacluster_key in enumerate(metaclusters.keys()):
    metacluster = metaclusters[metacluster_key]
    display(vdomh.h3("Metacluster %d/%d" % (metacluster_i + 1, num_metaclusters)))
    patterns = metacluster.seqlets_to_patterns_result.patterns
    if not patterns:
        break
    motif_pfms.append([])
    motif_hcwms.append([])
    motif_cwms.append([])
    motif_pfms_short.append([])
    num_seqlets.append([])
    motif_seqlets.append([])
    num_patterns = len(patterns)
    for pattern_i, pattern in enumerate(patterns):
        seqlets = pattern.seqlets
        display(vdomh.h4("Pattern %d/%d" % (pattern_i + 1, num_patterns)))
        display(vdomh.p("%d seqlets" % len(seqlets)))
        
        pfm = pattern["sequence"].fwd
        hcwm = pattern["task0_hypothetical_contribs"].fwd
        cwm = pattern["task0_contrib_scores"].fwd
        
        pfm_fig = viz_sequence.plot_weights(pfm, subticks_frequency=10, return_fig=True)
        hcwm_fig = viz_sequence.plot_weights(hcwm, subticks_frequency=10, return_fig=True)
        cwm_fig = viz_sequence.plot_weights(cwm, subticks_frequency=10, return_fig=True)
        pfm_fig.tight_layout()
        hcwm_fig.tight_layout()
        cwm_fig.tight_layout()
        
        motif_table = vdomh.table(
            vdomh.tr(
                vdomh.td("Sequence (PFM)"),
                vdomh.td(util.figure_to_vdom_image(pfm_fig))
            ),
            vdomh.tr(
                vdomh.td("Hypothetical contributions (hCWM)"),
                vdomh.td(util.figure_to_vdom_image(hcwm_fig))
            ),
            vdomh.tr(
                vdomh.td("Actual contributions (CWM)"),
                vdomh.td(util.figure_to_vdom_image(cwm_fig))
            )
        )
        display(motif_table)
        plt.close("all")  # Remove all standing figures
        
        # Trim motif based on total contribution
        score = np.sum(np.abs(cwm), axis=1)
        trim_thresh = np.max(score) * 0.2  # Cut off anything less than 20% of max score
        pass_inds = np.where(score >= trim_thresh)[0]
        
        short_trimmed_pfm = pfm[np.min(pass_inds): np.max(pass_inds) + 1]
        motif_pfms_short[-1].append(short_trimmed_pfm)
        
        # Expand trimming to +/- 4bp on either side
        start, end = max(0, np.min(pass_inds) - 4), min(len(cwm), np.max(pass_inds) + 4 + 1)
        trimmed_pfm = pfm[start:end]
        trimmed_hcwm = hcwm[start:end]
        trimmed_cwm = cwm[start:end]
        
        motif_pfms[-1].append(trimmed_pfm)
        motif_hcwms[-1].append(trimmed_hcwm)
        motif_cwms[-1].append(trimmed_cwm)
        
        num_seqlets[-1].append(len(seqlets))
        
        seqlet_true_profs, seqlet_pred_profs, seqlet_seqs, seqlet_hyps, seqlet_coords = extract_profiles_and_coords(
            seqlets, one_hot_seqs, hyp_scores, true_profs, pred_profs, pred_coords,
            input_length, profile_length, shap_score_center_size,
            profile_display_center_size, task_index=task_index
        )
        
        motif_seqlets[-1].append((seqlet_seqs, seqlet_hyps))

        assert np.allclose(np.sum(seqlet_seqs, axis=0) / len(seqlet_seqs), pattern["sequence"].fwd)
        # ^Sanity check: PFM derived from seqlets match the PFM stored in the pattern
        plot_profiles(
            # Flatten to NT x O x 2
            np.reshape(seqlet_true_profs, (-1, seqlet_true_profs.shape[2], seqlet_true_profs.shape[3])),
            np.reshape(seqlet_pred_profs, (-1, seqlet_pred_profs.shape[2], seqlet_pred_profs.shape[3]))
        )
        
        summit_dists = get_summit_distances(seqlet_coords, peak_table)
        plot_summit_dists(summit_dists)

Metacluster 1/2

Pattern 1/3

8681 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Pattern 2/3

337 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Pattern 3/3

98 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Metacluster 2/2

Pattern 1/8

941 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Pattern 2/8

432 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Pattern 3/8

176 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Pattern 4/8

140 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Pattern 5/8

141 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Pattern 6/8

59 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Pattern 7/8

46 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Pattern 8/8

34 seqlets

Sequence (PFM)
Hypothetical contributions (hCWM)
Actual contributions (CWM)

Summary of motifs

Motifs are trimmed based on information content, and presented in descending order by number of supporting seqlets. The motifs are separated by metacluster. The motifs are presented as hCWMs. The forward orientation is defined as the orientation that is richer in purines.

In [16]:
colgroup = vdomh.colgroup(
    vdomh.col(style={"width": "5%"}),
    vdomh.col(style={"width": "5%"}),
    vdomh.col(style={"width": "45%"}),
    vdomh.col(style={"width": "45%"})
)
header = vdomh.thead(
    vdomh.tr(
        vdomh.th("#", style={"text-align": "center"}),
        vdomh.th("Seqlets", style={"text-align": "center"}),
        vdomh.th("Forward", style={"text-align": "center"}),
        vdomh.th("Reverse", style={"text-align": "center"})
    )
)

for i in range(len(motif_hcwms)):
    display(vdomh.h3("Metacluster %d/%d" % (i + 1, num_metaclusters)))
    body = []
    for j in range(len(motif_hcwms[i])):
        motif = motif_hcwms[i][j]
        if np.sum(motif[:, [0, 2]]) > 0.5 * np.sum(motif):
            # Forward is purine-rich, reverse-complement is pyrimidine-rich
            f, rc = motif, np.flip(motif, axis=(0, 1))
        else:
            f, rc = np.flip(motif, axis=(0, 1)), motif
            
        f_fig = viz_sequence.plot_weights(f, figsize=(20, 4), return_fig=True)
        f_fig.tight_layout()
        rc_fig = viz_sequence.plot_weights(rc, figsize=(20, 4), return_fig=True)
        rc_fig.tight_layout()

        body.append(
            vdomh.tr(
                vdomh.td(str(j + 1)),
                vdomh.td(str(num_seqlets[i][j])),
                vdomh.td(util.figure_to_vdom_image(f_fig)),
                vdomh.td(util.figure_to_vdom_image(rc_fig))
            )
        )
    display(vdomh.table(colgroup, header, vdomh.tbody(*body)))
    plt.close("all")

Metacluster 1/2

#SeqletsForwardReverse
18681
2337
398

Metacluster 2/2

#SeqletsForwardReverse
1941
2432
3176
4140
5141
659
746
834

Top TOMTOM matches for each motif

Here, the TF-MoDISco motifs are plotted as hCWMs, but the TOMTOM matches are shown as PWMs.

In [17]:
num_matches_to_keep = 10
num_matches_to_show = 5

header = vdomh.thead(
    vdomh.tr(
        vdomh.th("Motif ID", style={"text-align": "center"}),
        vdomh.th("q-val", style={"text-align": "center"}),
        vdomh.th("PWM", style={"text-align": "center"})
    )
)

for i in range(len(motif_pfms)):
    display(vdomh.h3("Metacluster %d/%d" % (i + 1, num_metaclusters)))
    
    # Compute TOMTOM matches for all motifs in the metacluster at once
    tomtom_matches = match_motifs_to_database(motif_pfms_short[i], top_k=num_matches_to_keep)
    
    for j in range(len(motif_pfms[i])):
        display(vdomh.h4("Motif %d/%d" % (j + 1, len(motif_pfms[i]))))
        viz_sequence.plot_weights(motif_hcwms[i][j])
    
        body = []
        for k, (match_name, match_pfm, match_qval) in enumerate(tomtom_matches[j]):
            fig = viz_sequence.plot_weights(util.pfm_to_pwm(match_pfm), return_fig=True)
            fig.tight_layout()
            if k < num_matches_to_show:
                body.append(
                    vdomh.tr(
                        vdomh.td(match_name),
                        vdomh.td(str(match_qval)),
                        vdomh.td(util.figure_to_vdom_image(fig))
                    )
                )
            else:
                body.append(
                    vdomh.tr(
                        vdomh.td(match_name),
                        vdomh.td(str(match_qval)),
                        vdomh.td("Not shown")
                    )
                )
        if not body:
            display(vdomh.p("No TOMTOM matches passing threshold"))
        else:
            display(vdomh.table(header, vdomh.tbody(*body)))
        plt.close("all")

Metacluster 1/2

Motif 1/3

Motif IDq-valPWM
MA0139.1_CTCF1.5661e-16
CTCF_HUMAN.H11MO.0.A4.0721400000000003e-16
CTCFL_HUMAN.H11MO.0.A1.64918e-08
MA1102.2_CTCFL5.79037e-05
MA1568.1_TCF21(var.2)0.214932
MA1638.1_HAND20.231864Not shown
SNAI1_HUMAN.H11MO.0.C0.231864Not shown
KLF8_HUMAN.H11MO.0.C0.368323Not shown
MA1628.1_Zic1::Zic20.368323Not shown
MA0155.1_INSM10.368323Not shown

Motif 2/3

No TOMTOM matches passing threshold

Motif 3/3

Motif IDq-valPWM
CPEB1_HUMAN.H11MO.0.D2.63381e-05
PRDM6_HUMAN.H11MO.0.C0.0267158
MA1125.1_ZNF3840.0267158
FOXL1_HUMAN.H11MO.0.D0.039919699999999995
FOXG1_HUMAN.H11MO.0.D0.058789
ANDR_HUMAN.H11MO.0.A0.109502Not shown
MA0679.2_ONECUT10.109502Not shown
FOXJ3_HUMAN.H11MO.0.A0.109502Not shown
ONEC2_HUMAN.H11MO.0.D0.13231199999999999Not shown
FUBP1_HUMAN.H11MO.0.D0.165131Not shown

Metacluster 2/2

Motif 1/8

Motif IDq-valPWM
CTCF_HUMAN.H11MO.0.A1.7760899999999999e-10
MA0139.1_CTCF3.1167700000000003e-10
CTCFL_HUMAN.H11MO.0.A3.4614699999999996e-09
MA1102.2_CTCFL8.94406e-06
MA1628.1_Zic1::Zic20.201327
PLAL1_HUMAN.H11MO.0.D0.201327Not shown
KLF8_HUMAN.H11MO.0.C0.201327Not shown
ZIC3_HUMAN.H11MO.0.B0.201327Not shown
SNAI1_HUMAN.H11MO.0.C0.22127800000000003Not shown
MA1548.1_PLAGL20.22127800000000003Not shown

Motif 2/8

Motif IDq-valPWM
TBX15_HUMAN.H11MO.0.D3.3800400000000004e-07
MAZ_HUMAN.H11MO.0.A3.3800400000000004e-07
KLF16_HUMAN.H11MO.0.D3.3800400000000004e-07
ZN467_HUMAN.H11MO.0.C3.3800400000000004e-07
SP1_HUMAN.H11MO.0.A3.7860399999999997e-07
SP2_HUMAN.H11MO.0.A3.7860399999999997e-07Not shown
SP3_HUMAN.H11MO.0.B1.1251399999999999e-06Not shown
PATZ1_HUMAN.H11MO.0.C1.5371200000000002e-06Not shown
VEZF1_HUMAN.H11MO.0.C1.5371200000000002e-06Not shown
WT1_HUMAN.H11MO.0.C2.5676599999999997e-06Not shown

Motif 3/8

Motif IDq-valPWM
SP2_HUMAN.H11MO.0.A0.00692795
SP3_HUMAN.H11MO.0.B0.013167400000000001
SP1_HUMAN.H11MO.1.A0.0155623
MA1653.1_ZNF1480.0178541
MA1522.1_MAZ0.0178541
SP4_HUMAN.H11MO.1.A0.0178541Not shown
SP2_HUMAN.H11MO.1.B0.0216658Not shown
MA0830.2_TCF40.0216658Not shown
MA0471.2_E2F60.03885809999999999Not shown
SP1_HUMAN.H11MO.0.A0.0494259Not shown

Motif 4/8

Motif IDq-valPWM
SP2_HUMAN.H11MO.0.A0.0025118000000000002
ZN263_HUMAN.H11MO.1.A0.0025118000000000002
MA1653.1_ZNF1480.00363601
MA0528.2_ZNF2630.00363601
WT1_HUMAN.H11MO.0.C0.00363601
SP3_HUMAN.H11MO.0.B0.00363601Not shown
MA1522.1_MAZ0.00363601Not shown
SP4_HUMAN.H11MO.1.A0.00393914Not shown
ZFX_HUMAN.H11MO.1.A0.0111005Not shown
SP2_HUMAN.H11MO.1.B0.016773Not shown

Motif 5/8

Motif IDq-valPWM
SP2_HUMAN.H11MO.0.A0.00244544
SP1_HUMAN.H11MO.0.A0.00388783
THAP1_HUMAN.H11MO.0.C0.015409899999999999
AP2D_HUMAN.H11MO.0.D0.015409899999999999
SP3_HUMAN.H11MO.0.B0.015409899999999999
MXI1_HUMAN.H11MO.0.A0.015409899999999999Not shown
USF2_HUMAN.H11MO.0.A0.0384293Not shown
MA0146.2_Zfx0.0384293Not shown
MA1615.1_Plagl10.0384293Not shown
AP2B_HUMAN.H11MO.0.B0.0384806Not shown

Motif 6/8

Motif IDq-valPWM
MXI1_HUMAN.H11MO.0.A0.000576544
SP2_HUMAN.H11MO.0.A0.000576544
SP1_HUMAN.H11MO.0.A0.000818342
SP3_HUMAN.H11MO.0.B0.000829413
SP1_HUMAN.H11MO.1.A0.00799938
MA1102.2_CTCFL0.00803746Not shown
KLF16_HUMAN.H11MO.0.D0.0107145Not shown
MA1513.1_KLF150.0124715Not shown
MA1650.1_ZBTB140.0124715Not shown
KLF3_HUMAN.H11MO.0.B0.0124715Not shown

Motif 7/8

Motif IDq-valPWM
SP2_HUMAN.H11MO.0.A0.0156727
MA1522.1_MAZ0.0238266
MA0146.2_Zfx0.0238266
MA1513.1_KLF150.028527999999999998
MA0103.3_ZEB10.053793499999999994
SP3_HUMAN.H11MO.0.B0.053793499999999994Not shown
SP1_HUMAN.H11MO.0.A0.0561615Not shown
KLF3_HUMAN.H11MO.0.B0.05803200000000001Not shown
MA1653.1_ZNF1480.05803200000000001Not shown
MA0522.3_TCF30.05803200000000001Not shown

Motif 8/8

Motif IDq-valPWM
SP3_HUMAN.H11MO.0.B8.42746e-09
SP1_HUMAN.H11MO.0.A2.19082e-07
TBX15_HUMAN.H11MO.0.D5.666429999999999e-07
SP2_HUMAN.H11MO.0.A6.67234e-07
MAZ_HUMAN.H11MO.0.A9.76934e-07
ZN467_HUMAN.H11MO.0.C1.20746e-06Not shown
WT1_HUMAN.H11MO.0.C1.27031e-06Not shown
KLF16_HUMAN.H11MO.0.D1.4019899999999998e-06Not shown
VEZF1_HUMAN.H11MO.0.C4.00147e-06Not shown
PATZ1_HUMAN.H11MO.0.C5.17077e-06Not shown

Sample of seqlets supporting each motif

Here, the motifs are presented as hCWMs, along with the actual importance scores of a random sample of seqlets that support the motif.

In [18]:
num_seqlets_to_show = 10

colgroup = vdomh.colgroup(
    vdomh.col(style={"width": "50%"}),
    vdomh.col(style={"width": "50%"})
)

header = vdomh.thead(
    vdomh.tr(
        vdomh.th("Motif hCWM", style={"text-align": "center"}),
        vdomh.th("Seqlets", style={"text-align": "center"})
    )
)

for i in range(len(motif_hcwms)):
    display(vdomh.h3("Metacluster %d/%d" % (i + 1, num_metaclusters)))
    
    for j in range(len(motif_hcwms[i])):
        display(vdomh.h4("Motif %d/%d" % (j + 1, len(motif_hcwms[i]))))
        
        motif_fig = viz_sequence.plot_weights(motif_hcwms[i][j], figsize=(20, 4), return_fig=True)
        motif_fig.tight_layout()
        
        seqlet_seqs, seqlet_hyps = motif_seqlets[i][j]
        
        sample_size = min(num_seqlets_to_show, len(seqlet_seqs))
        sample_inds = np.random.choice(len(seqlet_seqs), size=sample_size, replace=False)
        sample = []
        for k in sample_inds:
            fig = viz_sequence.plot_weights(seqlet_hyps[k] * seqlet_seqs[k], subticks_frequency=10, return_fig=True)
            fig.tight_layout()
            sample.append(util.figure_to_vdom_image(fig))
        body = vdomh.tbody(vdomh.tr(vdomh.td(util.figure_to_vdom_image(motif_fig)), vdomh.td(*sample)))
        display(vdomh.table(colgroup, header, body))
        plt.close("all")

Metacluster 1/2

Motif 1/3

Motif hCWMSeqlets

Motif 2/3

Motif hCWMSeqlets

Motif 3/3

Motif hCWMSeqlets

Metacluster 2/2

Motif 1/8

Motif hCWMSeqlets

Motif 2/8

Motif hCWMSeqlets

Motif 3/8

Motif hCWMSeqlets

Motif 4/8

Motif hCWMSeqlets

Motif 5/8

Motif hCWMSeqlets

Motif 6/8

Motif hCWMSeqlets

Motif 7/8

Motif hCWMSeqlets

Motif 8/8

Motif hCWMSeqlets