bblean 0.6.0b1__cp311-cp311-macosx_10_9_universal2.whl

bblean/cli.py

@@ -0,0 +1,1854 @@
+r"""Command line interface entrypoints"""
+
+import warnings
+import random
+import typing as tp
+import math
+import shutil
+import sys
+import pickle
+import multiprocessing as mp
+import multiprocessing.shared_memory as shmem
+from typing import Annotated
+from pathlib import Path
+
+from typer import Typer, Argument, Option, Abort, Context, Exit
+
+from bblean._memory import launch_monitor_rss_daemon
+from bblean._timer import Timer
+from bblean._config import DEFAULTS, collect_system_specs_and_dump_config, TSNE_SEED
+from bblean.utils import _import_bitbirch_variant, batched
+
+app = Typer(
+    rich_markup_mode="markdown",
+    add_completion=False,
+    help=r"""CLI tool for serial or parallel fast clustering of molecular fingerprints
+    using the memory-efficient and compute-efficient *O(N)* BitBIRCH algorithm ('Lean'
+    version). For more info about the subcommands run `bb <subcommand> --help `.""",
+)
+
+
+def _print_help_banner(ctx: Context, value: bool) -> None:
+    if value:
+        from bblean._console import get_console
+
+        console = get_console()
+        console.print_banner()
+        console.print(ctx.get_help())
+        raise Exit()
+
+
+def _validate_output_dir(out_dir: Path, overwrite: bool = False) -> None:
+    if out_dir.exists():
+        if not out_dir.is_dir():
+            raise RuntimeError("Output dir should be a dir")
+        if any(out_dir.iterdir()):
+            if overwrite:
+                shutil.rmtree(out_dir)
+            else:
+                raise RuntimeError(f"Output dir {out_dir} has files")
+
+
+# Validate that the naming convention for the input files is correct
+def _validate_input_dir(in_dir: Path | str) -> None:
+    in_dir = Path(in_dir)
+    if not in_dir.is_dir():
+        raise RuntimeError(f"Input dir {in_dir} should be a dir")
+    if not any(in_dir.glob("*.npy")):
+        raise RuntimeError(f"Input dir {in_dir} should have *.npy fingerprint files")
+
+
+@app.callback()
+def _main(
+    ctx: Context,
+    help_: Annotated[
+        bool,
+        Option(
+            "--help/ ",
+            "-h",
+            is_eager=True,
+            help="Show this message and exit.",
+            callback=_print_help_banner,
+        ),
+    ] = False,
+) -> None:
+    pass
+
+
+@app.command("plot-pops", rich_help_panel="Analysis")
+def _plot_pops(
+    clusters_path: Annotated[
+        Path,
+        Argument(help="Path to the clusters file, or a dir with a clusters.pkl file"),
+    ],
+    fps_path: Annotated[
+        Path | None,
+        Option(
+            "-f",
+            "--fps-path",
+            help="Path to fingerprint file, or directory with fingerprint files",
+            show_default=False,
+        ),
+    ] = None,
+    title: Annotated[
+        str | None,
+        Option("--title", help="Plot title"),
+    ] = None,
+    top: Annotated[
+        int | None,
+        Option("--top"),
+    ] = None,
+    input_is_packed: Annotated[
+        bool,
+        Option("--packed-input/--unpacked-input", rich_help_panel="Advanced"),
+    ] = True,
+    min_size: Annotated[
+        int,
+        Option("--min-size"),
+    ] = 0,
+    n_features: Annotated[
+        int | None,
+        Option(
+            "--n-features",
+            help="Number of features in the fingerprints."
+            " Only for packed inputs *if it is not a multiple of 8*."
+            " Not required for typical fingerprint sizes (e.g. 2048, 1024)",
+            rich_help_panel="Advanced",
+        ),
+    ] = None,
+    save: Annotated[
+        bool,
+        Option("--save/--no-save"),
+    ] = True,
+    filename: Annotated[
+        str | None,
+        Option("--filename"),
+    ] = None,
+    verbose: Annotated[
+        bool,
+        Option("-v/-V", "--verbose/--no-verbose"),
+    ] = True,
+    show: Annotated[
+        bool,
+        Option("--show/--no-show", hidden=True),
+    ] = True,
+) -> None:
+    r"""Population plot of the clustering results"""
+    from bblean._console import get_console
+
+    console = get_console(silent=not verbose)
+    # Imports may take a bit of time since sklearn is slow, so start the spinner here
+    with console.status("[italic]Analyzing clusters...[/italic]", spinner="dots"):
+        from bblean.plotting import _dispatch_visualization, pops_plot
+
+        _dispatch_visualization(
+            clusters_path,
+            "pops",
+            pops_plot,
+            {},
+            min_size=min_size,
+            top=top,
+            n_features=n_features,
+            input_is_packed=input_is_packed,
+            fps_path=fps_path,
+            title=title,
+            filename=filename,
+            verbose=verbose,
+            save=save,
+            show=show,
+        )
+
+
+@app.command("plot-umap", rich_help_panel="Analysis")
+def _plot_umap(
+    clusters_path: Annotated[
+        Path,
+        Argument(help="Path to the clusters file, or a dir with a clusters.pkl file"),
+    ],
+    fps_path: Annotated[
+        Path | None,
+        Option(
+            "-f",
+            "--fps-path",
+            help="Path to fingerprint file, or directory with fingerprint files",
+            show_default=False,
+        ),
+    ] = None,
+    title: Annotated[
+        str | None,
+        Option("--title", help="Plot title"),
+    ] = None,
+    save: Annotated[
+        bool,
+        Option("--save/--no-save"),
+    ] = True,
+    top: Annotated[
+        int,
+        Option("--top"),
+    ] = 20,
+    input_is_packed: Annotated[
+        bool,
+        Option("--packed-input/--unpacked-input", rich_help_panel="Advanced"),
+    ] = True,
+    scaling: Annotated[
+        str,
+        Option("--scaling", rich_help_panel="Advanced"),
+    ] = "normalize",
+    min_size: Annotated[
+        int,
+        Option("--min-size"),
+    ] = 0,
+    n_features: Annotated[
+        int | None,
+        Option(
+            "--n-features",
+            help="Number of features in the fingerprints."
+            " Only for packed inputs *if it is not a multiple of 8*."
+            " Not required for typical fingerprint sizes (e.g. 2048, 1024)",
+            rich_help_panel="Advanced",
+        ),
+    ] = None,
+    filename: Annotated[
+        str | None,
+        Option("--filename"),
+    ] = None,
+    verbose: Annotated[
+        bool,
+        Option("-v/-V", "--verbose/--no-verbose"),
+    ] = True,
+    show: Annotated[
+        bool,
+        Option("--show/--no-show", hidden=True),
+    ] = True,
+    deterministic: Annotated[
+        bool,
+        Option("--deterministic/--no-deterministic"),
+    ] = False,
+    n_neighbors: Annotated[
+        int,
+        Option("-n", "--neighbors"),
+    ] = 15,
+    min_dist: Annotated[
+        float,
+        Option("-d", "--min-dist"),
+    ] = 0.5,
+    metric: Annotated[
+        str,
+        Option("--metric"),
+    ] = "euclidean",
+    densmap: Annotated[
+        bool,
+        Option("--densmap/--no-densmap"),
+    ] = False,
+    workers: Annotated[
+        int | None,
+        Option(
+            "-w",
+            "--workers",
+            help="Num. cores to use for parallel processing",
+            rich_help_panel="Advanced",
+        ),
+    ] = None,
+) -> None:
+    r"""UMAP visualization of the clustering results"""
+    from bblean._console import get_console
+
+    console = get_console(silent=not verbose)
+    # Imports may take a bit of time since sklearn is slow, so start the spinner here
+    with console.status("[italic]Analyzing clusters...[/italic]", spinner="dots"):
+        from bblean.plotting import _dispatch_visualization, umap_plot
+
+        kwargs = dict(
+            metric=metric,
+            densmap=densmap,
+            deterministic=deterministic,
+            n_neighbors=n_neighbors,
+            workers=workers,
+            min_dist=min_dist,
+        )
+        _dispatch_visualization(
+            clusters_path,
+            "umap",
+            umap_plot,
+            kwargs,
+            min_size=min_size,
+            top=top,
+            n_features=n_features,
+            input_is_packed=input_is_packed,
+            fps_path=fps_path,
+            title=title,
+            filename=filename,
+            verbose=verbose,
+            save=save,
+            show=show,
+        )
+
+
+@app.command("plot-pca", rich_help_panel="Analysis")
+def _plot_pca(
+    clusters_path: Annotated[
+        Path,
+        Argument(help="Path to the clusters file, or a dir with a clusters.pkl file"),
+    ],
+    fps_path: Annotated[
+        Path | None,
+        Option(
+            "-f",
+            "--fps-path",
+            help="Path to fingerprint file, or directory with fingerprint files",
+            show_default=False,
+        ),
+    ] = None,
+    title: Annotated[
+        str | None,
+        Option("--title", help="Plot title"),
+    ] = None,
+    top: Annotated[
+        int,
+        Option("--top"),
+    ] = 20,
+    min_size: Annotated[
+        int,
+        Option("--min-size"),
+    ] = 0,
+    input_is_packed: Annotated[
+        bool,
+        Option("--packed-input/--unpacked-input", rich_help_panel="Advanced"),
+    ] = True,
+    scaling: Annotated[
+        str,
+        Option("--scaling", rich_help_panel="Advanced"),
+    ] = "normalize",
+    n_features: Annotated[
+        int | None,
+        Option(
+            "--n-features",
+            help="Number of features in the fingerprints."
+            " Only for packed inputs *if it is not a multiple of 8*."
+            " Not required for typical fingerprint sizes (e.g. 2048, 1024)",
+            rich_help_panel="Advanced",
+        ),
+    ] = None,
+    verbose: Annotated[
+        bool,
+        Option("-v/-V", "--verbose/--no-verbose"),
+    ] = True,
+    show: Annotated[
+        bool,
+        Option("--show/--no-show", hidden=True),
+    ] = True,
+    whiten: Annotated[
+        bool,
+        Option("--whiten/--no-whiten"),
+    ] = False,
+    save: Annotated[
+        bool,
+        Option("--save/--no-save"),
+    ] = True,
+    filename: Annotated[
+        str | None,
+        Option("--filename"),
+    ] = None,
+) -> None:
+    r"""PCA visualization of the clustering results"""
+    from bblean._console import get_console
+
+    console = get_console(silent=not verbose)
+    # Imports may take a bit of time since sklearn is slow, so start the spinner here
+    with console.status("[italic]Analyzing clusters...[/italic]", spinner="dots"):
+        from bblean.plotting import _dispatch_visualization, pca_plot
+
+        _dispatch_visualization(
+            clusters_path,
+            "pca",
+            pca_plot,
+            {"whiten": whiten},
+            min_size=min_size,
+            top=top,
+            n_features=n_features,
+            input_is_packed=input_is_packed,
+            fps_path=fps_path,
+            title=title,
+            filename=filename,
+            verbose=verbose,
+            save=save,
+            show=show,
+        )
+
+
+@app.command("plot-tsne", rich_help_panel="Analysis")
+def _plot_tsne(
+    clusters_path: Annotated[
+        Path,
+        Argument(help="Path to the clusters file, or a dir with a clusters.pkl file"),
+    ],
+    fps_path: Annotated[
+        Path | None,
+        Option(
+            "-f",
+            "--fps-path",
+            help="Path to fingerprint file, or directory with fingerprint files",
+            show_default=False,
+        ),
+    ] = None,
+    title: Annotated[
+        str | None,
+        Option("--title", help="Plot title"),
+    ] = None,
+    save: Annotated[
+        bool,
+        Option("--save/--no-save"),
+    ] = True,
+    min_size: Annotated[
+        int,
+        Option("--min-size"),
+    ] = 0,
+    filename: Annotated[
+        str | None,
+        Option("--filename"),
+    ] = None,
+    exaggeration: Annotated[
+        float | None,
+        Option("-e", "--exaggeration", rich_help_panel="Advanced"),
+    ] = None,
+    seed: Annotated[
+        int | None,
+        Option(
+            "-s",
+            "--seed",
+            help=(
+                "Seed for the rng, fixed value by default, for reproducibility."
+                " Pass -1 to randomize"
+            ),
+            show_default=False,
+            rich_help_panel="Advanced",
+        ),
+    ] = TSNE_SEED,
+    top: Annotated[
+        int,
+        Option("--top"),
+    ] = 20,
+    metric: Annotated[
+        str,
+        Option("--metric", help="Metric to use in the t-SNE source space"),
+    ] = "euclidean",
+    dof: Annotated[
+        float,
+        Option("-d", "--dof", rich_help_panel="Advanced"),
+    ] = 1.0,
+    perplexity: Annotated[
+        int,
+        Option(help="t-SNE perplexity", rich_help_panel="Advanced"),
+    ] = 30,
+    input_is_packed: Annotated[
+        bool,
+        Option("--packed-input/--unpacked-input", rich_help_panel="Advanced"),
+    ] = True,
+    n_features: Annotated[
+        int | None,
+        Option(
+            "--n-features",
+            help="Number of features in the fingerprints."
+            " Only for packed inputs *if it is not a multiple of 8*."
+            " Not required for typical fingerprint sizes (e.g. 2048, 1024)",
+            rich_help_panel="Advanced",
+        ),
+    ] = None,
+    scaling: Annotated[
+        str,
+        Option("--scaling", rich_help_panel="Advanced"),
+    ] = "normalize",
+    do_pca_init: Annotated[
+        bool,
+        Option(
+            "--pca-init/--no-pca-init",
+            rich_help_panel="Advanced",
+            help="Use PCA for initialization",
+        ),
+    ] = True,
+    pca_reduce: Annotated[
+        int | None,
+        Option(
+            "-p",
+            "--pca-reduce",
+            rich_help_panel="Advanced",
+            help=(
+                "Reduce fingerprint dimensionality to N components using PCA."
+                " A value of 50 or more maintains cluster structure in general"
+            ),
+        ),
+    ] = None,
+    workers: Annotated[
+        int | None,
+        Option(
+            "-w",
+            "--workers",
+            help="Num. cores to use for parallel processing",
+            rich_help_panel="Advanced",
+        ),
+    ] = None,
+    multiscale: Annotated[
+        bool,
+        Option(
+            "-m/-M",
+            "--multiscale/--no-multiscale",
+            rich_help_panel="Advanced",
+            help="Use multiscale perplexities (WARNING: Can be very slow!)",
+        ),
+    ] = False,
+    verbose: Annotated[
+        bool,
+        Option("-v/-V", "--verbose/--no-verbose"),
+    ] = True,
+    show: Annotated[
+        bool,
+        Option("--show/--no-show", hidden=True),
+    ] = True,
+) -> None:
+    r"""t-SNE visualization of the clustering results"""
+    from bblean._console import get_console
+
+    console = get_console(silent=not verbose)
+    # Imports may take a bit of time since sklearn is slow, so start the spinner here
+    with console.status("[italic]Analyzing clusters...[/italic]", spinner="dots"):
+        from bblean.plotting import _dispatch_visualization, tsne_plot
+
+        kwargs = dict(
+            metric=metric,
+            seed=seed,
+            perplexity=perplexity,
+            exaggeration=exaggeration,
+            dof=dof,
+            workers=workers,
+            scaling=scaling,
+            do_pca_init=do_pca_init,
+            multiscale=multiscale,
+            pca_reduce=pca_reduce,
+        )
+        _dispatch_visualization(
+            clusters_path,
+            "tsne",
+            tsne_plot,
+            kwargs,
+            min_size=min_size,
+            top=top,
+            n_features=n_features,
+            input_is_packed=input_is_packed,
+            fps_path=fps_path,
+            title=title,
+            filename=filename,
+            verbose=verbose,
+            save=save,
+            show=show,
+        )
+
+
+@app.command("summary", rich_help_panel="Analysis")
+def _table_summary(
+    clusters_path: Annotated[
+        Path,
+        Argument(help="Path to the clusters file, or a dir with a clusters.pkl file"),
+    ],
+    fps_path: Annotated[
+        Path | None,
+        Option(
+            "-f",
+            "--fps-path",
+            help="Path to fingerprint file, or directory with fingerprint files",
+            show_default=False,
+        ),
+    ] = None,
+    min_size: Annotated[
+        int,
+        Option("--min-size"),
+    ] = 0,
+    smiles_path: Annotated[
+        Path | None,
+        Option(
+            "-s",
+            "--smiles-path",
+            show_default=False,
+            help="Optional smiles path, if passed a scaffold analysis is performed",
+        ),
+    ] = None,
+    top: Annotated[
+        int,
+        Option("--top"),
+    ] = 20,
+    input_is_packed: Annotated[
+        bool,
+        Option("--packed-input/--unpacked-input", rich_help_panel="Advanced"),
+    ] = True,
+    scaffold_fp_kind: Annotated[
+        str,
+        Option("--scaffold-fp-kind"),
+    ] = DEFAULTS.fp_kind,
+    n_features: Annotated[
+        int | None,
+        Option(
+            "--n-features",
+            help="Number of features in the fingerprints."
+            " Only for packed inputs *if it is not a multiple of 8*."
+            " Not required for typical fingerprint sizes (e.g. 2048, 1024)",
+            rich_help_panel="Advanced",
+        ),
+    ] = None,
+    metrics: Annotated[
+        bool,
+        Option(
+            "--metrics/--no-metrics",
+            help="Calculate clustering indices (Dunn, DBI, CHI)",
+        ),
+    ] = False,
+    chosen_metrics: Annotated[
+        str,
+        Option(
+            "-m",
+            "--metrics-choice",
+            help=(
+                "Chosen metrics. "
+                " Comma-separated list including dunn (slow), dbi or chi"
+            ),
+        ),
+    ] = "dunn,dbi,chi",
+    metrics_top: Annotated[
+        int | None,
+        Option("--metrics-top", rich_help_panel="Advanced"),
+    ] = 100,
+    metrics_min_size: Annotated[
+        int,
+        Option("--metrics-min-size", hidden=True),
+    ] = 1,
+    verbose: Annotated[
+        bool,
+        Option("--verbose/--no-verbose", hidden=True),
+    ] = True,
+) -> None:
+    r"""Summary table of clustering results, together with cluster metrics"""
+    from bblean._console import get_console
+    from bblean.smiles import load_smiles
+    from bblean.analysis import cluster_analysis
+    from bblean.utils import _has_files_or_valid_symlinks
+    from bblean.metrics import jt_dbi, jt_isim_chi, jt_isim_dunn, _calc_centrals
+    from rich.table import Table
+
+    console = get_console(silent=not verbose)
+    # Imports may take a bit of time since sklearn is slow, so start the spinner here
+    with console.status("[italic]Analyzing clusters...[/italic]", spinner="dots"):
+        if clusters_path.is_dir():
+            clusters_path = clusters_path / "clusters.pkl"
+        with open(clusters_path, mode="rb") as f:
+            clusters = pickle.load(f)
+        if fps_path is None:
+            input_fps_path = clusters_path.parent / "input-fps"
+            if input_fps_path.is_dir() and _has_files_or_valid_symlinks(input_fps_path):
+                fps_path = input_fps_path
+            else:
+                msg = (
+                    "Could not find input fingerprints. Please use --fps-path."
+                    " Summary plot without fingerprints doesn't include isim values"
+                )
+                warnings.warn(msg)
+        if fps_path is None:
+            fps_paths = None
+        elif fps_path.is_dir():
+            fps_paths = sorted(fps_path.glob("*.npy"))
+        else:
+            fps_paths = [fps_path]
+        ca = cluster_analysis(
+            clusters,
+            fps_paths,
+            smiles=load_smiles(smiles_path) if smiles_path is not None else (),
+            top=top,
+            n_features=n_features,
+            input_is_packed=input_is_packed,
+            min_size=min_size,
+        )
+        table = Table(title=(f"Top {top} clusters" if top is not None else "Clusters"))
+        table.add_column("Size", justify="center")
+        table.add_column("% fps", justify="center")
+        table.add_column("iSIM", justify="center")
+        if smiles_path is not None:
+            table.add_column("Size/Scaff.", justify="center")
+            table.add_column("Num. Scaff.", justify="center")
+            table.add_column("Scaff. iSIM", justify="center")
+        sizes = ca.sizes
+        isims = ca.isims
+        total_fps = ca.total_fps
+        for i in range(ca.clusters_num):
+            size = sizes[i]
+            percent = size / total_fps * 100
+            table.add_row(f"{size:,}", f"{percent:.2f}", f"{isims[i]:.3f}")
+        console.print(table)
+        console.print()
+        console.print(f"Total num. fps: {total_fps:,}")
+        console.print(f"Total num. clusters: {ca.all_clusters_num:,}")
+        singles = ca.all_singletons_num
+        singles_percent = singles * 100 / ca.all_clusters_num
+        console.print(f"Total num. singletons: {singles:,} ({singles_percent:.2f} %)")
+        gt10 = ca.all_clusters_num_with_size_above(10)
+        gt10_percent = gt10 * 100 / ca.all_clusters_num
+        console.print(
+            f"Total num. clusters, size > 10: {gt10:,} ({gt10_percent:.2f} %)"
+        )
+        gt100 = ca.all_clusters_num_with_size_above(100)
+        gt100_percent = gt100 * 100 / ca.all_clusters_num
+        console.print(
+            f"Total num. clusters, size > 100: {gt100:,} ({gt100_percent:.2f} %)"
+        )
+        console.print(
+            f"num-clusters/num-fps ratio: {ca.all_clusters_num / total_fps:.2f}"
+        )
+        console.print(f"Mean size: {ca.all_clusters_mean_size:.2f}")
+        console.print(f"Max. size: {ca.all_clusters_max_size:,}")
+        console.print(f"Q3 (75%) size: {ca.all_clusters_q3:,}")
+        console.print(f"Median size: {ca.all_clusters_median_size:,}")
+        console.print(f"Q1 (25%) size: {ca.all_clusters_q1:,}")
+        console.print(f"Min. size: {ca.all_clusters_min_size:,}")
+    if metrics:
+        chosen = set(s.lower() for s in chosen_metrics.split(","))
+        assert all(s in ["dunn", "chi", "dbi"] for s in chosen)
+        # Redo cluster analysis with more *top* clusters
+        console.print()
+        if metrics_top is None:
+            console.print("Clustering metrics:")
+        else:
+            console.print(f"Clustering metrics considering top {metrics_top} clusters:")
+        with console.status("[italic]Reanalyzing clusters...[/italic]", spinner="dots"):
+            ca = cluster_analysis(
+                clusters,
+                fps_paths,
+                smiles=(),
+                top=metrics_top,
+                n_features=n_features,
+                input_is_packed=input_is_packed,
+                min_size=metrics_min_size,
+            )
+            clusters = ca.get_top_cluster_fps()
+        with console.status("[italic]Calculating centrals...[/italic]", spinner="dots"):
+            centrals = _calc_centrals(clusters, kind="centroid")
+        if "chi" in chosen:
+            chi = jt_isim_chi(clusters, centrals=centrals, verbose=verbose)
+            console.print(f"    - CHI index: {chi:.4f} (Higher is better)")
+        if "dbi" in chosen:
+            dbi = jt_dbi(clusters, centrals=centrals, verbose=verbose)
+            console.print(f"    - DBI index: {dbi:.4e} (Lower is better)")
+        if "dunn" in chosen:
+            dunn = jt_isim_dunn(clusters, verbose=verbose)
+            console.print(f"    - Dunn index: {dunn:.4f} (Higher is better)")
+
+
+@app.command("plot-summary", rich_help_panel="Analysis")
+def _plot_summary(
+    clusters_path: Annotated[
+        Path,
+        Argument(help="Path to the clusters file, or a dir with a clusters.pkl file"),
+    ],
+    fps_path: Annotated[
+        Path | None,
+        Option(
+            "-f",
+            "--fps-path",
+            help="Path to fingerprint file, or directory with fingerprint files",
+            show_default=False,
+        ),
+    ] = None,
+    save: Annotated[
+        bool,
+        Option("--save/--no-save"),
+    ] = True,
+    ylim: Annotated[
+        int | None,
+        Option("--ylim"),
+    ] = None,
+    min_size: Annotated[
+        int,
+        Option("--min-size"),
+    ] = 0,
+    smiles_path: Annotated[
+        Path | None,
+        Option(
+            "-s",
+            "--smiles-path",
+            show_default=False,
+            help="Optional smiles path, if passed a scaffold analysis is performed",
+        ),
+    ] = None,
+    title: Annotated[
+        str | None,
+        Option("--title"),
+    ] = None,
+    filename: Annotated[
+        str | None,
+        Option("--filename"),
+    ] = None,
+    top: Annotated[
+        int,
+        Option("--top"),
+    ] = 20,
+    input_is_packed: Annotated[
+        bool,
+        Option("--packed-input/--unpacked-input", rich_help_panel="Advanced"),
+    ] = True,
+    scaffold_fp_kind: Annotated[
+        str,
+        Option("--scaffold-fp-kind"),
+    ] = DEFAULTS.fp_kind,
+    n_features: Annotated[
+        int | None,
+        Option(
+            "--n-features",
+            help="Number of features in the fingerprints."
+            " Only for packed inputs *if it is not a multiple of 8*."
+            " Not required for typical fingerprint sizes (e.g. 2048, 1024)",
+            rich_help_panel="Advanced",
+        ),
+    ] = None,
+    annotate: Annotated[
+        bool,
+        Option(
+            "--annotate/--no-annotate",
+            help="Display scaffold and fingerprint number in each cluster",
+        ),
+    ] = True,
+    verbose: Annotated[
+        bool,
+        Option("-v/-V", "--verbose/--no-verbose"),
+    ] = True,
+    show: Annotated[
+        bool,
+        Option("--show/--no-show", hidden=True),
+    ] = True,
+) -> None:
+    r"""Summary plot of the clustering results"""
+    from bblean._console import get_console
+
+    console = get_console(silent=not verbose)
+    # Imports may take a bit of time since sklearn is slow, so start the spinner here
+    with console.status("[italic]Analyzing clusters...[/italic]", spinner="dots"):
+        from bblean.plotting import _dispatch_visualization, summary_plot
+        from bblean.smiles import load_smiles
+
+        _dispatch_visualization(
+            clusters_path,
+            "summary",
+            summary_plot,
+            {"annotate": annotate, "counts_ylim": ylim},
+            smiles=load_smiles(smiles_path) if smiles_path is not None else (),
+            min_size=min_size,
+            top=top,
+            n_features=n_features,
+            input_is_packed=input_is_packed,
+            fps_path=fps_path,
+            title=title,
+            filename=filename,
+            verbose=verbose,
+            save=save,
+            show=show,
+        )
+
+
+@app.command("run")
+def _run(
+    ctx: Context,
+    input_: Annotated[
+        Path | None,
+        Argument(help="`*.npy` file with packed fingerprints, or dir `*.npy` files"),
+    ] = None,
+    out_dir: Annotated[
+        Path | None,
+        Option(
+            "-o",
+            "--out-dir",
+            help="Dir to dump the output files",
+        ),
+    ] = None,
+    overwrite: Annotated[bool, Option(help="Allow overwriting output files")] = False,
+    branching_factor: Annotated[
+        int,
+        Option(
+            "--branching",
+            "-b",
+            help="BitBIRCH branching factor (all rounds). Usually 254 is"
+            " optimal. Set above 254 for slightly less RAM (at the cost of some perf.)",
+        ),
+    ] = DEFAULTS.branching_factor,
+    threshold: Annotated[
+        float,
+        Option("--threshold", "-t", help="Threshold for merge criterion"),
+    ] = DEFAULTS.threshold,
+    refine_threshold_change: Annotated[
+        float,
+        Option(
+            "--refine-threshold-change",
+            help="Modify threshold for refinement criterion, can be negative",
+        ),
+    ] = DEFAULTS.refine_threshold_change,
+    save_tree: Annotated[
+        bool,
+        Option("--save-tree/--no-save-tree", rich_help_panel="Advanced"),
+    ] = False,
+    save_centroids: Annotated[
+        bool,
+        Option("--save-centroids/--no-save-centroids", rich_help_panel="Advanced"),
+    ] = True,
+    merge_criterion: Annotated[
+        str,
+        Option("--set-merge", "-m", help="Merge criterion for initial clustsering"),
+    ] = DEFAULTS.merge_criterion,
+    refine_merge_criterion: Annotated[
+        str,
+        Option("--set-refine-merge", help="Merge criterion for refinement clustsering"),
+    ] = DEFAULTS.refine_merge_criterion,
+    tolerance: Annotated[
+        float,
+        Option(help="BitBIRCH tolerance. For refinement and --set-merge 'tolerance'"),
+    ] = DEFAULTS.tolerance,
+    refine_num: Annotated[
+        int,
+        Option(
+            "--refine-num",
+            help=(
+                "Num. of largest clusters to refine."
+                " 1 for standard refinement, 0 is the default (no refinement)"
+            ),
+        ),
+    ] = 0,
+    refine_rounds: Annotated[
+        int | None,
+        Option(
+            "--refine-rounds",
+            help=("Num. of refinement rounds. "),
+            hidden=True,
+        ),
+    ] = None,
+    recluster_rounds: Annotated[
+        int,
+        Option(
+            "--recluster-rounds",
+            help=("Num. of reclustering rounds. "),
+            hidden=True,
+        ),
+    ] = 0,
+    recluster_shuffle: Annotated[
+        bool,
+        Option("--recluster-shuffle/--no-recluster-shuffle", hidden=True),
+    ] = True,
+    n_features: Annotated[
+        int | None,
+        Option(
+            "--n-features",
+            help="Number of features in the fingerprints."
+            " It must be provided for packed inputs *if it is not a multiple of 8*."
+            " For typical fingerprint sizes (e.g. 2048, 1024), it is not required",
+            rich_help_panel="Advanced",
+        ),
+    ] = None,
+    input_is_packed: Annotated[
+        bool,
+        Option(
+            "--packed-input/--unpacked-input",
+            help="Toggle whether the input consists on packed or unpacked fingerprints",
+            rich_help_panel="Advanced",
+        ),
+    ] = True,
+    # Debug options
+    monitor_rss: Annotated[
+        bool,
+        Option(
+            "--monitor-mem/--no-monitor-mem",
+            "--monitor-rss/--no-monitor-rss",
+            help="Monitor RAM used by all processes",
+            rich_help_panel="Advanced",
+        ),
+    ] = True,
+    monitor_rss_interval_s: Annotated[
+        float,
+        Option(
+            "--monitor-mem-seconds",
+            "--monitor-rss-seconds",
+            help="Interval in seconds for RAM monitoring",
+            rich_help_panel="Debug",
+            hidden=True,
+        ),
+    ] = 1.0,
+    max_fps: Annotated[
+        int | None,
+        Option(
+            help="Max. num of fingerprints to read from each file",
+            rich_help_panel="Debug",
+            hidden=True,
+        ),
+    ] = None,
+    variant: Annotated[
+        str,
+        Option(
+            "--bb-variant",
+            help="Use different bitbirch variants, *only for debugging*.",
+            hidden=True,
+        ),
+    ] = "lean",
+    copy_inputs: Annotated[
+        bool,
+        Option(
+            "--copy/--no-copy",
+            rich_help_panel="Advanced",
+            help="Copy the input files instead of symlink",
+        ),
+    ] = False,
+    verbose: Annotated[
+        bool,
+        Option("-v/-V", "--verbose/--no-verbose"),
+    ] = True,
+) -> None:
+    r"""Run standard, serial BitBIRCH clustering over `*.npy` fingerprint files"""
+    # TODO: Remove code duplication with multiround
+    from bblean._console import get_console
+    from bblean.fingerprints import _get_fps_file_num
+
+    console = get_console(silent=not verbose)
+    if variant == "int64" and input_is_packed:
+        raise ValueError("Packed inputs are not supported for the int64 variant")
+    if refine_rounds is None:
+        refine_rounds = 1 if refine_num > 0 else 0
+    if refine_rounds > 0 and refine_num == 0:
+        refine_num = 1
+    ctx.params["refine_rounds"] = refine_rounds
+    ctx.params["refine_num"] = refine_num
+
+    BitBirch, set_merge = _import_bitbirch_variant(variant)
+
+    # NOTE: Files are sorted according to name
+    if input_ is None:
+        input_ = Path.cwd() / "bb_inputs"
+        input_.mkdir(exist_ok=True)
+        input_files = sorted(input_.glob("*.npy"))
+        _validate_input_dir(input_)
+    elif input_.is_dir():
+        input_files = sorted(input_.glob("*.npy"))
+        _validate_input_dir(input_)
+    else:
+        input_files = [input_]
+    ctx.params.pop("input_")
+    ctx.params["input_files"] = [str(p.resolve()) for p in input_files]
+    ctx.params["num_fps_present"] = [_get_fps_file_num(p) for p in input_files]
+    if max_fps is not None:
+        ctx.params["num_fps_loaded"] = [
+            min(n, max_fps) for n in ctx.params["num_fps_present"]
+        ]
+    else:
+        ctx.params["num_fps_loaded"] = ctx.params["num_fps_present"]
+    unique_id = format(random.getrandbits(32), "08x")
+    if out_dir is None:
+        out_dir = Path.cwd() / "bb_run_outputs" / unique_id
+    out_dir.mkdir(exist_ok=True, parents=True)
+    _validate_output_dir(out_dir, overwrite)
+    ctx.params["out_dir"] = str(out_dir.resolve())
+
+    console.print_banner()
+    console.print()
+    console.print_config(ctx.params)
+
+    # Optinally start a separate process that tracks RAM usage
+    if monitor_rss:
+        launch_monitor_rss_daemon(out_dir / "monitor-rss.csv", monitor_rss_interval_s)
+
+    timer = Timer()
+    timer.init_timing("total")
+    if "lean" not in variant:
+        set_merge(merge_criterion, tolerance=tolerance)
+        tree = BitBirch(branching_factor=branching_factor, threshold=threshold)
+    else:
+        tree = BitBirch(
+            branching_factor=branching_factor,
+            threshold=threshold,
+            merge_criterion=merge_criterion,
+            tolerance=tolerance,
+        )
+    with console.status("[italic]BitBirching...[/italic]", spinner="dots"):
+        for file in input_files:
+            # Fitting a file uses mmap internally, and releases memory in a smart way
+            tree.fit(
+                file,
+                n_features=n_features,
+                input_is_packed=input_is_packed,
+                max_fps=max_fps,
+            )
+    if recluster_rounds != 0 or refine_rounds != 0:
+        tree.set_merge(
+            refine_merge_criterion,
+            tolerance=tolerance,
+            threshold=threshold + refine_threshold_change,
+        )
+        for r in range(refine_rounds):
+            msg = (
+                f"[italic]Refinement, round {r + 1}"
+                f" (will split {refine_num} largest clusters)...[/italic]"
+            )
+            with console.status(msg, spinner="dots"):
+                tree.refine_inplace(
+                    input_files,
+                    input_is_packed=input_is_packed,
+                    n_largest=refine_num,
+                )
+        for r in range(recluster_rounds):
+            msg = f"[italic]Reclustering, round {r + 1}...[/italic]"
+            with console.status(msg, spinner="dots"):
+                tree.recluster_inplace(shuffle=recluster_shuffle)
+
+    timer.end_timing("total", console, indent=False)
+    console.print_peak_mem(out_dir, indent=False)
+    if variant == "lean":
+        if save_tree:
+            # TODO: BitBIRCH is highly recursive. pickling may crash python,
+            # an alternative solution would be better
+            _old_limit = sys.getrecursionlimit()
+            sys.setrecursionlimit(100_000)
+            with open(out_dir / "bitbirch.pkl", mode="wb") as f:
+                pickle.dump(tree, f)
+            sys.setrecursionlimit(_old_limit)
+        tree.delete_internal_nodes()
+        # Dump outputs (peak memory, timings, config, cluster ids)
+        if save_centroids:
+            output = tree.get_centroids_mol_ids()
+            with open(out_dir / "clusters.pkl", mode="wb") as f:
+                pickle.dump(output["mol_ids"], f)
+            with open(out_dir / "cluster-centroids-packed.pkl", mode="wb") as f:
+                pickle.dump(output["centroids"], f)
+        else:
+            with open(out_dir / "clusters.pkl", mode="wb") as f:
+                pickle.dump(tree.get_cluster_mol_ids(), f)
+
+    collect_system_specs_and_dump_config(ctx.params)
+    timer.dump(out_dir / "timings.json")
+
+    # Symlink or copy fingerprint files
+    input_fps_dir = (out_dir / "input-fps").resolve()
+    input_fps_dir.mkdir()
+    if copy_inputs:
+        for file in input_files:
+            shutil.copy(file, input_fps_dir / file.name)
+    else:
+        for file in input_files:
+            (input_fps_dir / file.name).symlink_to(file.resolve())
+
+
+# TODO: Currently sometimes after a round is triggered *more* files are output, since
+# the files are divided *both* by uint8/uint16 and the batch idx. I believe this is not
+# ideal
+@app.command("multiround")
+def _multiround(
+    ctx: Context,
+    in_dir: Annotated[
+        Path | None,
+        Argument(help="Directory with input `*.npy` files with packed fingerprints"),
+    ] = None,
+    out_dir: Annotated[
+        Path | None,
+        Option("-o", "--out-dir", help="Dir for output files"),
+    ] = None,
+    overwrite: Annotated[bool, Option(help="Allow overwriting output files")] = False,
+    num_initial_processes: Annotated[
+        int, Option("--ps", "--processes", help="Num. processes for first round")
+    ] = 10,
+    num_midsection_processes: Annotated[
+        int | None,
+        Option(
+            "--mid-ps",
+            "--mid-processes",
+            help="Num. processes for middle section rounds."
+            " These are be memory intensive,"
+            " you may want to use 50%-30% of --ps."
+            " Default is same as --ps",
+        ),
+    ] = None,
+    branching_factor: Annotated[
+        int,
+        Option(
+            "--branching",
+            "-b",
+            help="BitBIRCH branching factor (all rounds). Usually 254 is"
+            " optimal. Set above 254 for slightly less RAM (at the cost of some perf.)",
+        ),
+    ] = DEFAULTS.branching_factor,
+    threshold: Annotated[
+        float,
+        Option("--threshold", "-t", help="Thresh for merge criterion (initial step)"),
+    ] = DEFAULTS.threshold,
+    mid_threshold_change: Annotated[
+        float,
+        Option("--mid-threshold-change", help="Modify threshold for refinement"),
+    ] = DEFAULTS.refine_threshold_change,
+    initial_merge_criterion: Annotated[
+        str,
+        Option(
+            "--set-merge",
+            "-m",
+            help="Initial merge criterion for round 1. ('diameter' recommended)",
+        ),
+    ] = DEFAULTS.merge_criterion,
+    save_tree: Annotated[
+        bool,
+        Option("--save-tree/--no-save-tree", rich_help_panel="Advanced"),
+    ] = False,
+    save_centroids: Annotated[
+        bool,
+        Option("--save-centroids/--no-save-centroids", rich_help_panel="Advanced"),
+    ] = True,
+    mid_merge_criterion: Annotated[
+        str,
+        Option(
+            "--set-mid-merge",
+            help="Merge criterion for midsection rounds ('diameter' recommended)",
+        ),
+    ] = DEFAULTS.refine_merge_criterion,
+    tolerance: Annotated[
+        float,
+        Option(
+            help="Tolerance value for all steps that use the 'tolerance' criterion"
+            " (by default all except initial round)",
+        ),
+    ] = DEFAULTS.tolerance,
+    n_features: Annotated[
+        int | None,
+        Option(
+            "--n-features",
+            help="Number of features in the fingerprints."
+            " Only for packed inputs *if it is not a multiple of 8*."
+            " Not required for typical fingerprint sizes (e.g. 2048, 1024)",
+            rich_help_panel="Advanced",
+        ),
+    ] = None,
+    input_is_packed: Annotated[
+        bool,
+        Option(
+            "--packed-input/--unpacked-input",
+            help="Toggle whether the input consists on packed or unpacked fingerprints",
+            rich_help_panel="Advanced",
+        ),
+    ] = True,
+    # Advanced options
+    num_midsection_rounds: Annotated[
+        int,
+        Option(
+            "--num-mid-rounds",
+            help="Number of midsection rounds to perform",
+            rich_help_panel="Advanced",
+        ),
+    ] = 1,
+    split_largest_after_midsection: Annotated[
+        bool,
+        Option(
+            "--split-after-mid/--no-split-after-mid",
+            help=(
+                "Split largest cluster after each midsection round"
+                " (to be refined by the next round)"
+            ),
+            rich_help_panel="Advanced",
+        ),
+    ] = False,
+    refinement_before_midsection: Annotated[
+        str,
+        Option(
+            "--initial-refine",
+            help=(
+                "Run a *full* refinement step after the initial clustering round,"
+                " only *split* largest cluster, or do *none*."
+            ),
+            rich_help_panel="Advanced",
+        ),
+    ] = "full",
+    max_tasks_per_process: Annotated[
+        int, Option(help="Max tasks per process", rich_help_panel="Advanced")
+    ] = 1,
+    fork: Annotated[
+        bool,
+        Option(
+            help="In linux, force the 'fork' multiprocessing start method",
+            rich_help_panel="Advanced",
+        ),
+    ] = False,
+    bin_size: Annotated[
+        int,
+        Option(help="Bin size for chunking during Round 2", rich_help_panel="Advanced"),
+    ] = 10,
+    # Debug options
+    variant: Annotated[
+        str,
+        Option(
+            "--bb-variant",
+            help="Use different bitbirch variants, *only for debugging*.",
+            hidden=True,
+        ),
+    ] = "lean",
+    monitor_rss: Annotated[
+        bool,
+        Option(
+            "--monitor-mem",
+            "--monitor-rss",
+            help="Monitor RAM used by all processes",
+            rich_help_panel="Advanced",
+        ),
+    ] = True,
+    monitor_rss_interval_s: Annotated[
+        float,
+        Option(
+            "--monitor-mem-seconds",
+            "--monitor-rss-seconds",
+            help="Interval in seconds for RAM monitoring",
+            rich_help_panel="Debug",
+            hidden=True,
+        ),
+    ] = 1.0,
+    max_fps: Annotated[
+        int | None,
+        Option(
+            help="Max num. of fps to load from each input file",
+            rich_help_panel="Debug",
+            hidden=True,
+        ),
+    ] = None,
+    max_files: Annotated[
+        int | None,
+        Option(help="Max num. files to read", rich_help_panel="Debug", hidden=True),
+    ] = None,
+    copy_inputs: Annotated[
+        bool,
+        Option(
+            "--copy/--no-copy",
+            rich_help_panel="Advanced",
+            help="Copy the input files instead of symlink",
+        ),
+    ] = False,
+    verbose: Annotated[
+        bool,
+        Option("-v/-V", "--verbose/--no-verbose"),
+    ] = True,
+    cleanup: Annotated[
+        bool,
+        Option("--cleanup/--no-cleanup", hidden=True),
+    ] = True,
+) -> None:
+    r"""Run multi-round BitBIRCH clustering, optionally parallelize over `*.npy` files"""  # noqa:E501
+    from bblean._console import get_console
+    from bblean.multiround import run_multiround_bitbirch
+    from bblean.fingerprints import _get_fps_file_num
+
+    console = get_console(silent=not verbose)
+
+    # Set multiprocessing start method
+    if fork and not sys.platform == "linux":
+        console.print("'fork' is only available on Linux", style="red")
+        raise Abort()
+    if sys.platform == "linux":
+        mp_context = mp.get_context("fork" if fork else "forkserver")
+    else:
+        mp_context = mp.get_context()
+
+    # Collect inputs:
+    # If not passed, input dir is bb_inputs/
+    if in_dir is None:
+        in_dir = Path.cwd() / "bb_inputs"
+    _validate_input_dir(in_dir)
+    # All files in the input dir with *.npy suffix are considered input files
+    input_files = sorted(in_dir.glob("*.npy"))[:max_files]
+    ctx.params["input_files"] = [str(p.resolve()) for p in input_files]
+    ctx.params["num_fps"] = [_get_fps_file_num(p) for p in input_files]
+    if max_fps is not None:
+        ctx.params["num_fps_loaded"] = [min(n, max_fps) for n in ctx.params["num_fps"]]
+    else:
+        ctx.params["num_fps_loaded"] = ctx.params["num_fps"]
+
+    # Set up outputs:
+    # If not passed, output dir is constructed as bb_multiround_outputs/<unique-id>/
+    unique_id = format(random.getrandbits(32), "08x")
+    if out_dir is None:
+        out_dir = Path.cwd() / "bb_multiround_outputs" / unique_id
+    out_dir.mkdir(exist_ok=True, parents=True)
+    _validate_output_dir(out_dir, overwrite)
+    ctx.params["out_dir"] = str(out_dir.resolve())
+
+    console.print_banner()
+    console.print()
+    console.print_multiround_config(ctx.params, mp_context)
+
+    # Optinally start a separate process that tracks RAM usage
+    if monitor_rss:
+        launch_monitor_rss_daemon(out_dir / "monitor-rss.csv", monitor_rss_interval_s)
+
+    timer = run_multiround_bitbirch(
+        input_files=input_files,
+        n_features=n_features,
+        input_is_packed=input_is_packed,
+        out_dir=out_dir,
+        initial_merge_criterion=initial_merge_criterion,
+        midsection_merge_criterion=mid_merge_criterion,
+        num_initial_processes=num_initial_processes,
+        num_midsection_processes=num_midsection_processes,
+        branching_factor=branching_factor,
+        threshold=threshold,
+        midsection_threshold_change=mid_threshold_change,
+        tolerance=tolerance,
+        # Advanced
+        save_tree=save_tree,
+        save_centroids=save_centroids,
+        bin_size=bin_size,
+        max_tasks_per_process=max_tasks_per_process,
+        refinement_before_midsection=refinement_before_midsection,
+        num_midsection_rounds=num_midsection_rounds,
+        split_largest_after_each_midsection_round=split_largest_after_midsection,
+        # Debug
+        max_fps=max_fps,
+        verbose=verbose,
+        mp_context=mp_context,
+        cleanup=cleanup,
+    )
+    timer.dump(out_dir / "timings.json")
+    # TODO: Also dump peak-rss.json
+    collect_system_specs_and_dump_config(ctx.params)
+
+    # Symlink or copy fingerprint files
+    input_fps_dir = (out_dir / "input-fps").resolve()
+    input_fps_dir.mkdir()
+    if copy_inputs:
+        for file in input_files:
+            shutil.copy(file, input_fps_dir / file.name)
+    else:
+        for file in input_files:
+            (input_fps_dir / file.name).symlink_to(file.resolve())
+
+
+@app.command("fps-info", rich_help_panel="Fingerprints")
+def _fps_info(
+    fp_paths: Annotated[
+        list[Path] | None,
+        Argument(show_default=False, help="Paths to *.smi files with smiles"),
+    ] = None,
+) -> None:
+    """Show info about a `*.npy` fingerprint file, or a dir with `*.npy` files"""
+    from bblean._console import get_console
+    from bblean.fingerprints import _print_fps_file_info
+
+    console = get_console()
+    if fp_paths is None:
+        fp_paths = [Path.cwd()]
+
+    for path in fp_paths:
+        if path.is_dir():
+            for file in path.glob("*.npy"):
+                _print_fps_file_info(file, console)
+        elif path.suffix == ".npy":
+            _print_fps_file_info(file, console)
+
+
+@app.command("fps-from-smiles", rich_help_panel="Fingerprints")
+def _fps_from_smiles(
+    smiles_paths: Annotated[
+        list[Path] | None,
+        Argument(show_default=False, help="Paths to *.smi files with smiles"),
+    ] = None,
+    out_dir: Annotated[
+        Path | None,
+        Option("-o", "--out-dir", show_default=False),
+    ] = None,
+    out_name: Annotated[
+        str | None,
+        Option("--name", help="Base name of output file"),
+    ] = None,
+    kind: Annotated[
+        str,
+        Option("-k", "--kind"),
+    ] = DEFAULTS.fp_kind,
+    fp_size: Annotated[
+        int,
+        Option("--n-features", help="Num. features of the generated fingerprints"),
+    ] = DEFAULTS.n_features,
+    parts: Annotated[
+        int | None,
+        Option(
+            "-n", "--num-parts", help="Split the created file into this number of parts"
+        ),
+    ] = None,
+    max_fps_per_file: Annotated[
+        int | None,
+        Option(
+            "-m",
+            "--max-fps-per-file",
+            help="Max. number of fps per file. Mutually exclusive with --num-parts",
+            show_default=False,
+        ),
+    ] = None,
+    pack: Annotated[
+        bool,
+        Option(
+            "-p/-P",
+            "--pack/--no-pack",
+            help="Pack bits in last dimension of fingerprints",
+            rich_help_panel="Advanced",
+        ),
+    ] = True,
+    dtype: Annotated[
+        str,
+        Option(
+            "-d",
+            "--dtype",
+            help="NumPy dtype for the generated fingerprints",
+            rich_help_panel="Advanced",
+        ),
+    ] = "uint8",
+    verbose: Annotated[
+        bool,
+        Option("-v/-V", "--verbose/--no-verbose"),
+    ] = True,
+    num_ps: Annotated[
+        int | None,
+        Option(
+            "--ps",
+            "--processes",
+            help=(
+                "Num. processes for multprocess generation."
+                " One process per file is used for multi-file generation"
+            ),
+        ),
+    ] = None,
+    sanitize: Annotated[
+        str,
+        Option(
+            "--sanitize",
+            help="RDKit sanitization operations to perform ('all' or 'minimal')",
+        ),
+    ] = "all",
+    skip_invalid: Annotated[
+        bool,
+        Option(
+            "--skip-invalid/--no-skip-invalid",
+            help=(
+                "Skip invalid smiles."
+                " If False, an error is raised on invalid smiles. If True they are"
+                " silently skipped (this is be more memory intensive, especially for"
+                " parallel processing)"
+            ),
+        ),
+    ] = False,
+) -> None:
+    r"""Generate a `*.npy` fingerprints file from one or more `*.smi` smiles files
+
+    By default this function runs in parallel and uses all available CPUs. In order to
+    use the memory efficient BitBIRCH u8 algorithm you should keep the defaults:
+    --dtype=uint8 and --pack
+    """
+    import numpy as np
+
+    from bblean._console import get_console
+    from bblean.utils import _num_avail_cpus
+    from bblean.fingerprints import _FingerprintFileCreator, _FingerprintArrayFiller
+    from bblean.smiles import (
+        calc_num_smiles,
+        _iter_ranges_and_smiles_batches,
+        _iter_idxs_and_smiles_batches,
+    )
+
+    # Force forkserver since rdkit may use threads, and fork is unsafe with threads
+    mp_context = mp.get_context("forkserver" if sys.platform == "linux" else None)
+
+    console = get_console(silent=not verbose)
+
+    if smiles_paths is None:
+        smiles_paths = list(Path.cwd().glob("*.smi"))
+    if not smiles_paths:
+        console.print("No *.smi files found", style="red")
+        raise Abort()
+
+    smiles_num = calc_num_smiles(smiles_paths)
+
+    def parse_num_per_batch(
+        smiles_num: int, parts: int | None, max_fps_per_file: int | None
+    ) -> tuple[int, int, int | None]:
+        digits: int | None
+        if parts is not None and max_fps_per_file is None:
+            num_per_batch = math.ceil(smiles_num / parts)
+            digits = len(str(parts))
+        elif parts is None and max_fps_per_file is not None:
+            num_per_batch = max_fps_per_file
+            parts = math.ceil(smiles_num / max_fps_per_file)
+            digits = len(str(parts))
+        elif parts is None and max_fps_per_file is None:
+            parts = 1
+            num_per_batch = math.ceil(smiles_num / parts)
+            digits = None
+        else:
+            raise ValueError("parts and max_fps_per_file are mutually exclusive")
+        return parts, num_per_batch, digits
+
+    try:
+        parts, num_per_batch, digits = parse_num_per_batch(
+            smiles_num, parts, max_fps_per_file
+        )
+    except ValueError:
+        console.print(
+            "'--max-fps-per-file' and '--num-parts' are mutually exclusive",
+            style="red",
+        )
+        raise Abort() from None
+    if out_dir is None:
+        out_dir = Path.cwd()
+    out_dir.mkdir(exist_ok=True)
+    out_dir = out_dir.resolve()
+
+    # Pass 2: build the molecules
+    unique_id = format(random.getrandbits(32), "08x")
+    if out_name is None:
+        # Save the fingerprints as a NumPy array
+        out_name = f"{'packed-' if pack else ''}fps-{dtype}-{kind}-{unique_id}"
+    else:
+        # Strip suffix
+        if out_name.endswith(".npy"):
+            out_name = out_name[:-4]
+
+    if num_ps is None:
+        # Get the number of cores *available for use for this process*
+        # bound by the number of parts to avoid spawning useless processes
+        if parts == 1:
+            num_ps = _num_avail_cpus()
+        else:
+            num_ps = min(_num_avail_cpus(), parts)
+    create_fp_file = _FingerprintFileCreator(
+        dtype,
+        out_dir,
+        out_name,
+        digits,
+        pack,
+        kind,
+        fp_size,
+        sanitize=sanitize,
+        skip_invalid=skip_invalid,
+        verbose=verbose,
+    )
+    timer = Timer()
+    timer.init_timing("total")
+    if parts > 1 and num_ps is not None and num_ps > 1:
+        # Multiprocessing version, 1 process per file
+        with console.status(
+            f"[italic]Generating fingerprints ({parts} files, parallel, {num_ps} procs.) ...[/italic]",  # noqa:E501
+            spinner="dots",
+        ):
+            with mp_context.Pool(processes=num_ps) as pool:
+                pool.map(
+                    create_fp_file,
+                    _iter_idxs_and_smiles_batches(smiles_paths, num_per_batch),
+                )
+        timer.end_timing("total", console, indent=False)
+        stem = out_name.split(".")[0]
+        console.print(f"Finished. Outputs written to {str(out_dir / stem)}.<idx>.npy")
+        return
+
+    # Parallel or serial, single file version
+    msg = "parallel" if num_ps > 1 else "serial"
+    with console.status(
+        f"[italic]Generating fingerprints ({parts} files, {msg}, {num_ps} procs.) ...[/italic]",  # noqa:E501
+        spinner="dots",
+    ):
+        if pack:
+            out_dim = (fp_size + 7) // 8
+        else:
+            out_dim = fp_size
+        shmem_size = smiles_num * out_dim * np.dtype(dtype).itemsize
+        fps_shmem = shmem.SharedMemory(create=True, size=shmem_size)
+        invalid_mask_shmem = shmem.SharedMemory(create=True, size=smiles_num)
+        fps_array_filler = _FingerprintArrayFiller(
+            shmem_name=fps_shmem.name,
+            invalid_mask_shmem_name=invalid_mask_shmem.name,
+            kind=kind,
+            fp_size=fp_size,
+            num_smiles=smiles_num,
+            dtype=dtype,
+            pack=pack,
+            sanitize=sanitize,
+            skip_invalid=skip_invalid,
+        )
+        if num_ps > 1 and parts == 1:
+            # Split into batches anyways if we have a single batch but multiple
+            # processes
+            _, num_per_batch, _ = parse_num_per_batch(
+                smiles_num, num_ps, max_fps_per_file
+            )
+        with mp_context.Pool(processes=num_ps) as pool:
+            pool.starmap(
+                fps_array_filler,
+                _iter_ranges_and_smiles_batches(smiles_paths, num_per_batch),
+            )
+        fps = np.ndarray((smiles_num, out_dim), dtype=dtype, buffer=fps_shmem.buf)
+        mask = np.ndarray((smiles_num,), dtype=np.bool, buffer=invalid_mask_shmem.buf)
+        if skip_invalid:
+            prev_num = len(fps)
+            fps = np.delete(fps, mask, axis=0)
+            new_num = len(fps)
+            console.print(f"Generated {new_num} fingerprints")
+            console.print(f"Skipped {prev_num - new_num} invalid smiles")
+            invalid_name = f"invalid-{unique_id}.npy"
+            console.print(
+                f"Invalid smiles idxs written to {str(out_dir / invalid_name)}"
+            )
+            np.save(out_dir / f"invalid-{unique_id}.npy", mask.nonzero()[0].reshape(-1))
+
+        np.save(
+            out_dir / out_name,
+            fps,
+        )
+        del mask
+        del fps
+        # Cleanup
+        fps_shmem.unlink()
+        invalid_mask_shmem.unlink()
+    timer.end_timing("total", console, indent=False)
+    console.print(f"Finished. Outputs written to {str(out_dir / out_name)}.npy")
+
+
+@app.command("fps-split", rich_help_panel="Fingerprints")
+def _split_fps(
+    input_: Annotated[
+        Path,
+        Argument(help="`*.npy` file with fingerprints"),
+    ],
+    out_dir: Annotated[
+        Path | None,
+        Option("-o", "--out-dir", show_default=False),
+    ] = None,
+    parts: Annotated[
+        int | None,
+        Option(
+            "-n",
+            "--num-parts",
+            help="Num. of parts to split file into. Mutually exclusive with --max-fps",
+            show_default=False,
+        ),
+    ] = None,
+    max_fps_per_file: Annotated[
+        int | None,
+        Option(
+            "-m",
+            "--max-fps",
+            help="Max. number of fps per file. Mutually exclusive with --num-parts",
+            show_default=False,
+        ),
+    ] = None,
+) -> None:
+    r"""Split a `*.npy` fingerprint file into multiple `*.npy` files
+
+    Usage to split into multiple files with a max number of fps each (e.g. 10k) is `bb
+    split-fps --max-fps 10_000 ./fps.npy --out-dir ./split`. To split into a pre-defined
+    number of parts (e.g. 10) `bb split-fps --num-parts 10 ./fps.npy --out-dir ./split`.
+    """
+    from bblean._console import get_console
+    import numpy as np
+
+    console = get_console()
+    if parts is not None and parts < 2:
+        console.print("Num must be >= 2", style="red")
+        raise Abort()
+    fps = np.load(input_, mmap_mode="r")
+    if parts is not None and max_fps_per_file is None:
+        num_per_batch = math.ceil(fps.shape[0] / parts)
+        digits = len(str(parts))
+    elif parts is None and max_fps_per_file is not None:
+        num_per_batch = max_fps_per_file
+        digits = len(str(math.ceil(fps.shape[0] / max_fps_per_file)))
+    else:
+        console.print(
+            "One and only one of '--max-fps' and '--num-parts' required", style="red"
+        )
+        raise Abort()
+
+    stem = input_.name.split(".")[0]
+    with console.status("[italic]Splitting fingerprints...[/italic]", spinner="dots"):
+        i = -1
+        for i, batch in enumerate(batched(fps, num_per_batch)):
+            suffixes = input_.suffixes
+            name = f"{stem}{''.join(suffixes[:-1])}.{str(i).zfill(digits)}.npy"
+
+            # Generate out dir when first fp file is being saved
+            if out_dir is None:
+                out_dir = Path.cwd() / stem
+            out_dir.mkdir(exist_ok=True)
+            out_dir = out_dir.resolve()
+
+            np.save(out_dir / name, batch)
+
+        if i == -1:
+            console.print("Warning: No fingerprints written", style="yellow")
+            return
+    console.print(
+        f"Finished. Outputs written to {str(tp.cast(Path, out_dir) / stem)}.<idx>.npy"
+    )
+
+
+@app.command("fps-shuffle", rich_help_panel="Fingerprints")
+def _shuffle_fps(
+    in_file: Annotated[
+        Path,
+        Argument(help="`*.npy` file with packed fingerprints"),
+    ],
+    out_dir: Annotated[
+        Path | None,
+        Option("-o", "--out-dir", show_default=False),
+    ] = None,
+    seed: Annotated[
+        int | None,
+        Option("--seed", hidden=True, rich_help_panel="Debug"),
+    ] = None,
+) -> None:
+    """Shuffle a fingerprints file
+
+    This function is not optimized and as such may have high RAM usage. It is
+    meant for testing purposes only"""
+    import numpy as np
+
+    fps = np.load(in_file)
+    stem = in_file.stem
+    rng = np.random.default_rng(seed)
+    rng.shuffle(fps, axis=0)
+    if out_dir is None:
+        out_dir = Path.cwd()
+    out_dir.mkdir(exist_ok=True)
+    out_dir = out_dir.resolve()
+    np.save(out_dir / f"shuffled-{stem}.npy", fps)
+
+
+@app.command("fps-merge", rich_help_panel="Fingerprints")
+def _merge_fps(
+    in_dir: Annotated[
+        Path,
+        Argument(help="Directory with input `*.npy` files with packed fingerprints"),
+    ],
+    out_dir: Annotated[
+        Path | None,
+        Option("-o", "--out-dir", show_default=False),
+    ] = None,
+) -> None:
+    r"""Merge a dir with multiple `*.npy` fingerprint file into a single `*.npy` file"""
+    from bblean._console import get_console
+    import numpy as np
+
+    console = get_console()
+
+    if out_dir is None:
+        out_dir = Path.cwd()
+    out_dir.mkdir(exist_ok=True)
+    out_dir = out_dir.resolve()
+    arrays = []
+    with console.status("[italic]Merging fingerprints...[/italic]", spinner="dots"):
+        stem = None
+        for f in sorted(in_dir.glob("*.npy")):
+            if stem is None:
+                stem = f.name.split(".")[0]
+            elif stem != f.name.split(".")[0]:
+                raise ValueError(
+                    "Name convention must be <name>.<idx>.npy"
+                    " with all files having the same <name>"
+                )
+            arrays.append(np.load(f))
+        if stem is None:
+            console.print("No *.npy files found")
+            return
+        np.save(out_dir / stem, np.concatenate(arrays))
+    console.print(f"Finished. Outputs written to {str(out_dir / stem)}.npy")