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/ENCSR000BKM/profile_predictions.h5
DeepSHAP scores path: /users/zahoor/TF-Atlas/02-16-2021/shap/ENCSR000BKM/profile_scores_alex_format.h5
TF-MoDISco results path: /users/zahoor/TF-Atlas/02-16-2021/modisco/ENCSR000BKM/profile/modisco_results.hd5
Peaks path: /users/zahoor/TF-Atlas/data/idr_peaks//ENCFF242YZU.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%|██████████| 22/22 [00:06<00:00,  3.58it/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 1/1

Pattern 1/9

9059 seqlets

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

Pattern 2/9

695 seqlets

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

Pattern 3/9

71 seqlets

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

Pattern 4/9

67 seqlets

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

Pattern 5/9

65 seqlets

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

Pattern 6/9

81 seqlets

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

Pattern 7/9

55 seqlets

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

Pattern 8/9

57 seqlets

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

Pattern 9/9

38 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 1/1

#SeqletsForwardReverse
19059
2695
371
467
565
681
755
857
938

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 1/1

Motif 1/9

Motif IDq-valPWM
GATA2_HUMAN.H11MO.0.A1.10049e-09
GATA1_HUMAN.H11MO.0.A0.0009263489999999999
TAL1_HUMAN.H11MO.0.A0.0009263489999999999
GATA4_HUMAN.H11MO.0.A0.012155899999999999
GATA1_HUMAN.H11MO.1.A0.0201947
GATA2_HUMAN.H11MO.1.A0.0201947Not shown
GATA3_HUMAN.H11MO.0.A0.0475029Not shown
MA0036.3_GATA20.0505214Not shown
GATA6_HUMAN.H11MO.0.A0.0658582Not shown
MA0482.2_GATA40.0732721Not shown

Motif 2/9

Motif IDq-valPWM
FOSL1_HUMAN.H11MO.0.A6.451390000000001e-07
FOSL2_HUMAN.H11MO.0.A6.680100000000001e-07
JUN_HUMAN.H11MO.0.A7.34134e-07
MA0489.1_JUN(var.2)9.2411e-07
JUND_HUMAN.H11MO.0.A1.08289e-06
MA1144.1_FOSL2::JUND6.40837e-06Not shown
MA1135.1_FOSB::JUNB7.40885e-06Not shown
MA1138.1_FOSL2::JUNB7.40885e-06Not shown
MA0478.1_FOSL28.70471e-06Not shown
MA0477.2_FOSL11.3088599999999999e-05Not shown

Motif 3/9

Motif IDq-valPWM
MA0037.3_GATA30.000177706
GATA2_HUMAN.H11MO.1.A0.000890688
MA0766.2_GATA50.000890688
MA0036.3_GATA20.00555745
GATA1_HUMAN.H11MO.1.A0.00578997
GATA4_HUMAN.H11MO.0.A0.00830561Not shown
GATA3_HUMAN.H11MO.0.A0.00871587Not shown
TAL1_HUMAN.H11MO.0.A0.00958375Not shown
GATA2_HUMAN.H11MO.0.A0.0114812Not shown
GATA1_HUMAN.H11MO.0.A0.014897299999999999Not shown

Motif 4/9

Motif IDq-valPWM
OLIG2_HUMAN.H11MO.1.B0.0109375
MA1472.1_BHLHA15(var.2)0.09438730000000001
ATOH1_HUMAN.H11MO.0.B0.09438730000000001
PTF1A_HUMAN.H11MO.1.B0.09438730000000001
LYL1_HUMAN.H11MO.0.A0.09438730000000001
NDF2_HUMAN.H11MO.0.B0.0945005Not shown
MA1467.1_ATOH1(var.2)0.0945005Not shown
MA0665.1_MSC0.125325Not shown
MA0816.1_Ascl20.125325Not shown
FOXC2_HUMAN.H11MO.0.D0.131924Not shown

Motif 5/9

Motif IDq-valPWM
OLIG2_HUMAN.H11MO.1.B0.0035861999999999995
LYL1_HUMAN.H11MO.0.A0.019397400000000002
NDF2_HUMAN.H11MO.0.B0.019397400000000002
NDF1_HUMAN.H11MO.0.A0.019397400000000002
ATOH1_HUMAN.H11MO.0.B0.019397400000000002
MA0665.1_MSC0.0330346Not shown
MA1467.1_ATOH1(var.2)0.0330346Not shown
MA1472.1_BHLHA15(var.2)0.0330834Not shown
MA0091.1_TAL1::TCF30.0347904Not shown
MA0667.1_MYF60.043989Not shown

Motif 6/9

Motif IDq-valPWM
MA1472.1_BHLHA15(var.2)0.00601984
MA0816.1_Ascl20.00601984
LYL1_HUMAN.H11MO.0.A0.00601984
OLIG1_HUMAN.H11MO.0.D0.00601984
OLIG2_HUMAN.H11MO.1.B0.00836597
MA1467.1_ATOH1(var.2)0.0114053Not shown
BHE22_HUMAN.H11MO.0.D0.0114053Not shown
MA0665.1_MSC0.0114053Not shown
ZN317_HUMAN.H11MO.0.C0.0119941Not shown
ASCL2_HUMAN.H11MO.0.D0.0121946Not shown

Motif 7/9

Motif IDq-valPWM
GATA6_HUMAN.H11MO.0.A0.0372414
TAL1_HUMAN.H11MO.0.A0.054278999999999994
MA1104.2_GATA60.0547539
GATA2_HUMAN.H11MO.0.A0.0547539
GATA4_HUMAN.H11MO.0.A0.130679
MA0037.3_GATA30.16400399999999998Not shown
GATA1_HUMAN.H11MO.0.A0.16400399999999998Not shown
MA0029.1_Mecom0.16400399999999998Not shown
GATA5_HUMAN.H11MO.0.D0.200975Not shown
GATA3_HUMAN.H11MO.0.A0.367261Not shown

Motif 8/9

Motif IDq-valPWM
GATA4_HUMAN.H11MO.0.A0.20747800000000002
GATA2_HUMAN.H11MO.1.A0.346831
GATA1_HUMAN.H11MO.1.A0.47356800000000004
MA0766.2_GATA50.47356800000000004
MA0036.3_GATA20.47356800000000004
GATA3_HUMAN.H11MO.0.A0.47356800000000004Not shown
MA0037.3_GATA30.47356800000000004Not shown

Motif 9/9

Motif IDq-valPWM
MA0036.3_GATA20.027977600000000002
MA0037.3_GATA30.027977600000000002
GATA6_HUMAN.H11MO.0.A0.027977600000000002
GATA2_HUMAN.H11MO.1.A0.0361672
Z324A_HUMAN.H11MO.0.C0.037268199999999994
MA0482.2_GATA40.037268199999999994Not shown
GATA3_HUMAN.H11MO.0.A0.037268199999999994Not shown
MA0766.2_GATA50.037268199999999994Not shown
GATA4_HUMAN.H11MO.0.A0.06606210000000001Not shown
MA1104.2_GATA60.06702430000000001Not 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 1/1

Motif 1/9

Motif hCWMSeqlets

Motif 2/9

Motif hCWMSeqlets

Motif 3/9

Motif hCWMSeqlets

Motif 4/9

Motif hCWMSeqlets

Motif 5/9

Motif hCWMSeqlets

Motif 6/9

Motif hCWMSeqlets

Motif 7/9

Motif hCWMSeqlets

Motif 8/9

Motif hCWMSeqlets

Motif 9/9

Motif hCWMSeqlets