kidney.py

"""This file contains code for use with "Think Bayes",
by Allen B. Downey, available from greenteapress.com

Copyright 2012 Allen B. Downey
License: GNU GPLv3 http://www.gnu.org/licenses/gpl.html
"""
from __future__ import print_function

import math
import numpy
import random
import sys

import correlation
import thinkplot
import matplotlib.pyplot as pyplot
import thinkbayes


INTERVAL = 245/365.0
FORMATS = ['pdf', 'eps']
MINSIZE = 0.2
MAXSIZE = 20
BUCKET_FACTOR = 10


def log2(x, denom=math.log(2)):
    """Computes log base 2."""
    return math.log(x) / denom


def SimpleModel():
    """Runs calculations based on a simple model."""

    # time between discharge and diagnosis, in days
    interval = 3291.0

    # doubling time in linear measure is doubling time in volume * 3
    dt = 811.0 * 3

    # number of doublings since discharge
    doublings = interval / dt

    # how big was the tumor at time of discharge (diameter in cm)
    d1 = 15.5
    d0 = d1 / 2.0 ** doublings

    print('interval (days)', interval)
    print('interval (years)', interval / 365)
    print('dt', dt)
    print('doublings', doublings)
    print('d1', d1)
    print('d0', d0)

    # assume an initial linear measure of 0.1 cm
    d0 = 0.1
    d1 = 15.5

    # how many doublings would it take to get from d0 to d1
    doublings = log2(d1 / d0)

    # what linear doubling time does that imply?
    dt = interval / doublings

    print('doublings', doublings)
    print('dt', dt)

    # compute the volumetric doubling time and RDT
    vdt = dt / 3
    rdt = 365 / vdt

    print('vdt', vdt)
    print('rdt', rdt)

    cdf = MakeCdf()
    p = cdf.Prob(rdt)
    print('Prob{RDT > 2.4}', 1-p)


def MakeCdf():
    """Uses the data from Zhang et al. to construct a CDF."""
    n = 53.0
    freqs = [0, 2, 31, 42, 48, 51, 52, 53]
    ps = [freq/n for freq in freqs]
    xs = numpy.arange(-1.5, 6.5, 1.0)

    cdf = thinkbayes.Cdf(xs, ps)
    return cdf


def PlotCdf(cdf):
    """Plots the actual and fitted distributions.

    cdf: CDF object
    """
    xs, ps = cdf.xs, cdf.ps
    cps = [1-p for p in ps]

    # CCDF on logy scale: shows exponential behavior
    thinkplot.Clf()
    thinkplot.Plot(xs, cps, 'bo-')
    thinkplot.Save(root='kidney1',
                formats=FORMATS,
                xlabel='RDT',
                ylabel='CCDF (log scale)',
                yscale='log')

    # CDF, model and data

    thinkplot.Clf()
    thinkplot.PrePlot(num=2)
    mxs, mys = ModelCdf()
    thinkplot.Plot(mxs, mys, label='model', linestyle='dashed') 

    thinkplot.Plot(xs, ps, 'gs', label='data')
    thinkplot.Save(root='kidney2',
                formats=FORMATS,
                xlabel='RDT (volume doublings per year)',
                ylabel='CDF',
                title='Distribution of RDT',
                axis=[-2, 7, 0, 1],
                loc=4)


def QQPlot(cdf, fit):
    """Makes a QQPlot of the values from actual and fitted distributions.

    cdf: actual Cdf of RDT
    fit: model
    """
    xs = [-1.5, 5.5]
    thinkplot.Clf()
    thinkplot.Plot(xs, xs, 'b-')

    xs, ps = cdf.xs, cdf.ps
    fs = [fit.Value(p) for p in ps]

    thinkplot.Plot(xs, fs, 'gs')
    thinkplot.Save(root = 'kidney3',
                formats=FORMATS,
                xlabel='Actual',
                ylabel='Model')
    

def FitCdf(cdf):
    """Fits a line to the log CCDF and returns the slope.

    cdf: Cdf of RDT
    """
    xs, ps = cdf.xs, cdf.ps
    cps = [1-p for p in ps]

    xs = xs[1:-1]
    lcps = [math.log(p) for p in cps[1:-1]]
    
    _inter, slope = correlation.LeastSquares(xs, lcps)
    return -slope


def CorrelatedGenerator(cdf, rho):
    """Generates a sequence of values from cdf with correlation.

    Generates a correlated standard Gaussian series, then transforms to
    values from cdf

    cdf: distribution to choose from
    rho: target coefficient of correlation
    """
    def Transform(x):
        """Maps from a Gaussian variate to a variate with the given CDF."""
        p = thinkbayes.GaussianCdf(x)
        y = cdf.Value(p)
        return y

    # for the first value, choose from a Gaussian and transform it
    x = random.gauss(0, 1)
    yield Transform(x)

    # for subsequent values, choose from the conditional distribution
    # based on the previous value
    sigma = math.sqrt(1 - rho**2)
    while True:
        x = random.gauss(x * rho, sigma)
        yield Transform(x)


def UncorrelatedGenerator(cdf, _rho=None):
    """Generates a sequence of values from cdf with no correlation.

    Ignores rho, which is accepted as a parameter to provide the
    same interface as CorrelatedGenerator

    cdf: distribution to choose from
    rho: ignored
    """
    while True:
        x = cdf.Random()
        yield x


def RdtGenerator(cdf, rho):
    """Returns an iterator with n values from cdf and the given correlation.

    cdf: Cdf object
    rho: coefficient of correlation
    """
    if rho == 0.0:
        return UncorrelatedGenerator(cdf)
    else:
        return CorrelatedGenerator(cdf, rho)


def GenerateRdt(pc, lam1, lam2):
    """Generate an RDT from a mixture of exponential distributions.

    With prob pc, generate a negative value with param lam2;
    otherwise generate a positive value with param lam1.
    """
    if random.random() < pc:
        return -random.expovariate(lam2)
    else:
        return random.expovariate(lam1)


def GenerateSample(n, pc, lam1, lam2):
    """Generates a sample of RDTs.

    n: sample size
    pc: probablity of negative growth
    lam1: exponential parameter of positive growth
    lam2: exponential parameter of negative growth

    Returns: list of random variates
    """
    xs = [GenerateRdt(pc, lam1, lam2) for _ in range(n)]
    return xs


def GenerateCdf(n=1000, pc=0.35, lam1=0.79, lam2=5.0):
    """Generates a sample of RDTs and returns its CDF.

    n: sample size
    pc: probablity of negative growth
    lam1: exponential parameter of positive growth
    lam2: exponential parameter of negative growth

    Returns: Cdf of generated sample
    """
    xs = GenerateSample(n, pc, lam1, lam2)
    cdf = thinkbayes.MakeCdfFromList(xs)
    return cdf


def ModelCdf(pc=0.35, lam1=0.79, lam2=5.0):
    """

    pc: probablity of negative growth
    lam1: exponential parameter of positive growth
    lam2: exponential parameter of negative growth

    Returns: list of xs, list of ys
    """
    cdf = thinkbayes.EvalExponentialCdf
    x1 = numpy.arange(-2, 0, 0.1)
    y1 = [pc * (1 - cdf(-x, lam2)) for x in x1]
    x2 = numpy.arange(0, 7, 0.1)
    y2 = [pc + (1-pc) * cdf(x, lam1) for x in x2]
    return list(x1) + list(x2), y1+y2


def BucketToCm(y, factor=BUCKET_FACTOR):
    """Computes the linear dimension for a given bucket.

    t: bucket number
    factor: multiplicitive factor from one bucket to the next

    Returns: linear dimension in cm
    """
    return math.exp(y / factor)


def CmToBucket(x, factor=BUCKET_FACTOR):
    """Computes the bucket for a given linear dimension.

    x: linear dimension in cm
    factor: multiplicitive factor from one bucket to the next

    Returns: float bucket number
    """
    return round(factor * math.log(x))


def Diameter(volume, factor=3/math.pi/4, exp=1/3.0):
    """Converts a volume to a diameter.

    d = 2r = 2 * (3/4/pi V)^1/3
    """
    return 2 * (factor * volume) ** exp


def Volume(diameter, factor=4*math.pi/3):
    """Converts a diameter to a volume.

    V = 4/3 pi (d/2)^3
    """
    return factor * (diameter/2.0)**3


class Cache(object):
    """Records each observation point for each tumor."""

    def __init__(self):
        """Initializes the cache.

        joint: map from (age, bucket) to frequency
        sequences: map from bucket to a list of sequences
        initial_rdt: sequence of (V0, rdt) pairs
        """
        self.joint = thinkbayes.Joint()
        self.sequences = {}
        self.initial_rdt = []

    def GetBuckets(self):
        """Returns an iterator for the keys in the cache."""
        return self.sequences.keys()

    def GetSequence(self, bucket):
        """Looks up a bucket in the cache."""
        return self.sequences[bucket]

    def ConditionalCdf(self, bucket, name=''):
        """Forms the cdf of ages for a given bucket.

        bucket: int bucket number
        name: string
        """
        pmf = self.joint.Conditional(0, 1, bucket, name=name)
        cdf = pmf.MakeCdf()
        return cdf

    def ProbOlder(self, cm, age):
        """Computes the probability of exceeding age, given size.

        cm: size in cm
        age: age in years
        """
        bucket = CmToBucket(cm)
        cdf = self.ConditionalCdf(bucket)
        p = cdf.Prob(age)
        return 1-p

    def GetDistAgeSize(self, size_thresh=MAXSIZE):
        """Gets the joint distribution of age and size.

        Map from (age, log size in cm) to log freq
        
        Returns: new Pmf object
        """
        joint = thinkbayes.Joint()

        for val, freq in self.joint.Items():
            age, bucket = val
            cm = BucketToCm(bucket)
            if cm > size_thresh:
                continue
            log_cm = math.log10(cm)
            joint.Set((age, log_cm), math.log(freq) * 10)

        return joint

    def Add(self, age, seq, rdt):
        """Adds this observation point to the cache.

        age: age of the tumor in years
        seq: sequence of volumes
        rdt: RDT during this interval
        """
        final = seq[-1]
        cm = Diameter(final)
        bucket = CmToBucket(cm)
        self.joint.Incr((age, bucket))

        self.sequences.setdefault(bucket, []).append(seq)

        initial = seq[-2]
        self.initial_rdt.append((initial, rdt))

    def Print(self):
        """Prints the size (cm) for each bucket, and the number of sequences."""
        for bucket in sorted(self.GetBuckets()):
            ss = self.GetSequence(bucket)
            diameter = BucketToCm(bucket)
            print(diameter, len(ss))
        
    def Correlation(self):
        """Computes the correlation between log volumes and rdts."""
        vs, rdts = zip(*self.initial_rdt)
        lvs = [math.log(v) for v in vs]
        return correlation.Corr(lvs, rdts)


class Calculator(object):
    """Encapsulates the state of the computation."""

    def __init__(self):
        """Initializes the cache."""
        self.cache = Cache()

    def MakeSequences(self, n, rho, cdf):
        """Returns a list of sequences of volumes.

        n: number of sequences to make
        rho: serial correlation
        cdf: Cdf of rdts

        Returns: list of n sequences of volumes
        """
        sequences = []
        for i in range(n):
            rdt_seq = RdtGenerator(cdf, rho)
            seq = self.MakeSequence(rdt_seq)
            sequences.append(seq)

            if i % 100 == 0:
                print(i)

        return sequences

    def MakeSequence(self, rdt_seq, v0=0.01, interval=INTERVAL, 
                     vmax=Volume(MAXSIZE)):
        """Simulate the growth of a tumor.

        rdt_seq: sequence of rdts
        v0: initial volume in mL (cm^3)
        interval: timestep in years
        vmax: volume to stop at

        Returns: sequence of volumes
        """
        seq = v0,
        age = 0

        for rdt in rdt_seq:
            age += interval
            final, seq = self.ExtendSequence(age, seq, rdt, interval)
            if final > vmax:
                break

        return seq

    def ExtendSequence(self, age, seq, rdt, interval):
        """Generates a new random value and adds it to the end of seq.

        Side-effect: adds sub-sequences to the cache.

        age: age of tumor at the end of this interval
        seq: sequence of values so far
        rdt: reciprocal doubling time in doublings per year
        interval: timestep in years

        Returns: final volume, extended sequence
        """
        initial = seq[-1]
        doublings = rdt * interval
        final = initial * 2**doublings
        new_seq = seq + (final,)
        self.cache.Add(age, new_seq, rdt)

        return final, new_seq

    def PlotBucket(self, bucket, color='blue'):
        """Plots the set of sequences for the given bucket.

        bucket: int bucket number
        color: string
        """
        sequences = self.cache.GetSequence(bucket)
        for seq in sequences:
            n = len(seq)
            age = n * INTERVAL
            ts = numpy.linspace(-age, 0, n)
            PlotSequence(ts, seq, color)

    def PlotBuckets(self):
        """Plots the set of sequences that ended in a given bucket."""
        # 2.01, 4.95 cm, 9.97 cm
        buckets = [7.0, 16.0, 23.0]
        buckets = [23.0]
        colors = ['blue', 'green', 'red', 'cyan']

        thinkplot.Clf()
        for bucket, color in zip(buckets, colors):
            self.PlotBucket(bucket, color)

        thinkplot.Save(root='kidney5',
                    formats=FORMATS,
                    title='History of simulated tumors',
                    axis=[-40, 1, MINSIZE, 12],
                    xlabel='years',
                    ylabel='diameter (cm, log scale)',
                    yscale='log')

    def PlotJointDist(self):
        """Makes a pcolor plot of the age-size joint distribution."""
        thinkplot.Clf()

        joint = self.cache.GetDistAgeSize()
        thinkplot.Contour(joint, contour=False, pcolor=True)

        thinkplot.Save(root='kidney8',
                    formats=FORMATS,
                    axis=[0, 41, -0.7, 1.31],
                    yticks=MakeLogTicks([0.2, 0.5, 1, 2, 5, 10, 20]),
                    xlabel='ages',
                    ylabel='diameter (cm, log scale)')

    def PlotConditionalCdfs(self):
        """Plots the cdf of ages for each bucket."""
        buckets = [7.0, 16.0, 23.0, 27.0]
        # 2.01, 4.95 cm, 9.97 cm, 14.879 cm
        names = ['2 cm', '5 cm', '10 cm', '15 cm']
        cdfs = []

        for bucket, name in zip(buckets, names):
            cdf = self.cache.ConditionalCdf(bucket, name)
            cdfs.append(cdf)

        thinkplot.Clf()
        thinkplot.PrePlot(num=len(cdfs))
        thinkplot.Cdfs(cdfs)
        thinkplot.Save(root='kidney6',
                    title='Distribution of age for several diameters',
                    formats=FORMATS,
                    xlabel='tumor age (years)',
                    ylabel='CDF',
                    loc=4)

    def PlotCredibleIntervals(self, xscale='linear'):
        """Plots the confidence interval for each bucket."""
        xs = []
        ts = []
        percentiles = [95, 75, 50, 25, 5]
        min_size = 0.3

        # loop through the buckets, accumulate
        # xs: sequence of sizes in cm
        # ts: sequence of percentile tuples
        for _, bucket in enumerate(sorted(self.cache.GetBuckets())):
            cm = BucketToCm(bucket)
            if cm < min_size or cm > 20.0:
                continue
            xs.append(cm)
            cdf = self.cache.ConditionalCdf(bucket)      
            ps = [cdf.Percentile(p) for p in percentiles]
            ts.append(ps)

        # dump the results into a table
        fp = open('kidney_table.tex', 'w')
        PrintTable(fp, xs, ts)
        fp.close()

        # make the figure
        linewidths = [1, 2, 3, 2, 1]
        alphas = [0.3, 0.5, 1, 0.5, 0.3]
        labels = ['95th', '75th', '50th', '25th', '5th']

        # transpose the ts so we have sequences for each percentile rank
        thinkplot.Clf()
        yys = zip(*ts)

        for ys, linewidth, alpha, label in zip(yys, linewidths, alphas, labels):
            options = dict(color='blue', linewidth=linewidth, 
                                alpha=alpha, label=label, markersize=2)

            # plot the data points
            thinkplot.Plot(xs, ys, 'bo', **options)

            # plot the fit lines
            fxs = [min_size, 20.0]
            fys = FitLine(xs, ys, fxs)

            thinkplot.Plot(fxs, fys, **options)

            # put a label at the end of each line
            x, y = fxs[-1], fys[-1]
            pyplot.text(x*1.05, y, label, color='blue',
                        horizontalalignment='left',
                        verticalalignment='center')

        # make the figure
        thinkplot.Save(root='kidney7',
                       formats=FORMATS,
                       title='Credible interval for age vs diameter',
                       xlabel='diameter (cm, log scale)',
                       ylabel='tumor age (years)',
                       xscale=xscale,
                       xticks=MakeTicks([0.5, 1, 2, 5, 10, 20]),
                       axis=[0.25, 35, 0, 45],
                       legend=False,
                       )


def PlotSequences(sequences):
    """Plots linear measurement vs time.

    sequences: list of sequences of volumes
    """
    thinkplot.Clf()

    options = dict(color='gray', linewidth=1, linestyle='dashed')
    thinkplot.Plot([0, 40], [10, 10], **options)

    for seq in sequences:
        n = len(seq)
        age = n * INTERVAL
        ts = numpy.linspace(0, age, n)
        PlotSequence(ts, seq)

    thinkplot.Save(root='kidney4',
                   formats=FORMATS,
                   axis=[0, 40, MINSIZE, 20],
                   title='Simulations of tumor growth',
                   xlabel='tumor age (years)',
                   yticks=MakeTicks([0.2, 0.5, 1, 2, 5, 10, 20]),
                   ylabel='diameter (cm, log scale)',
                   yscale='log')


def PlotSequence(ts, seq, color='blue'):
    """Plots a time series of linear measurements.

    ts: sequence of times in years
    seq: sequence of columes
    color: color string
    """
    options = dict(color=color, linewidth=1, alpha=0.2)
    xs = [Diameter(v) for v in seq]

    thinkplot.Plot(ts, xs, **options)


def PrintCI(fp, cm, ps):
    """Writes a line in the LaTeX table.

    fp: file pointer
    cm: diameter in cm
    ts: tuples of percentiles
    """
    fp.write('%0.1f' % round(cm, 1))
    for p in reversed(ps):
        fp.write(' & %0.1f ' % round(p, 1))
    fp.write(r'\\' '\n')


def PrintTable(fp, xs, ts):
    """Writes the data in a LaTeX table.

    fp: file pointer
    xs: diameters in cm
    ts: sequence of tuples of percentiles
    """
    fp.write(r'\begin{tabular}{|r||r|r|r|r|r|}' '\n')
    fp.write(r'\hline' '\n')
    fp.write(r'Diameter   & \multicolumn{5}{c|}{Percentiles of age} \\' '\n')
    fp.write(r'(cm)   & 5th & 25th & 50th & 75th & 95th \\' '\n')
    fp.write(r'\hline' '\n')

    for i, (cm, ps) in enumerate(zip(xs, ts)):
        #print(cm, ps)
        if i % 3 == 0:
            PrintCI(fp, cm, ps)

    fp.write(r'\hline' '\n')
    fp.write(r'\end{tabular}' '\n')


def FitLine(xs, ys, fxs):
    """Fits a line to the xs and ys, and returns fitted values for fxs.

    Applies a log transform to the xs.

    xs: diameter in cm
    ys: age in years
    fxs: diameter in cm
    """
    lxs = [math.log(x) for x in xs]
    inter, slope = correlation.LeastSquares(lxs, ys)
    # res = correlation.Residuals(lxs, ys, inter, slope)
    # r2 = correlation.CoefDetermination(ys, res)

    lfxs = [math.log(x) for x in fxs]
    fys = [inter + slope * x for x in lfxs]
    return fys


def MakeTicks(xs):
    """Makes a pair of sequences for use as pyplot ticks.

    xs: sequence of floats

    Returns (xs, labels), where labels is a sequence of strings.
    """
    labels = [str(x) for x in xs]
    return xs, labels


def MakeLogTicks(xs):
    """Makes a pair of sequences for use as pyplot ticks.

    xs: sequence of floats

    Returns (xs, labels), where labels is a sequence of strings.
    """
    lxs = [math.log10(x) for x in xs]
    labels = [str(x) for x in xs]
    return lxs, labels


def TestCorrelation(cdf):
    """Tests the correlated generator.

    Makes sure that the sequence has the right distribution and correlation.
    """
    n = 10000
    rho = 0.4

    rdt_seq = CorrelatedGenerator(cdf, rho)
    xs = [next(rdt_seq) for _ in range(n)]
    
    rho2 = correlation.SerialCorr(xs)
    print(rho, rho2)
    cdf2 = thinkbayes.MakeCdfFromList(xs)

    thinkplot.Cdfs([cdf, cdf2])
    thinkplot.Show()


def main(script):
    for size in [1, 5, 10]:
        bucket = CmToBucket(size)
        print('Size, bucket', size, bucket)

    SimpleModel()

    random.seed(17)

    cdf = MakeCdf()

    lam1 = FitCdf(cdf)
    fit = GenerateCdf(lam1=lam1)

    # TestCorrelation(fit)

    PlotCdf(cdf)
    # QQPlot(cdf, fit)

    calc = Calculator()
    rho = 0.0
    sequences = calc.MakeSequences(100, rho, fit)
    PlotSequences(sequences)

    calc.PlotBuckets()

    _ = calc.MakeSequences(1900, rho, fit)
    print('V0-RDT correlation', calc.cache.Correlation())

    print('15.5 Probability age > 8 year', calc.cache.ProbOlder(15.5, 8))
    print('6.0 Probability age > 8 year', calc.cache.ProbOlder(6.0, 8))

    calc.PlotConditionalCdfs()

    calc.PlotCredibleIntervals(xscale='log')

    calc.PlotJointDist()


if __name__ == '__main__':
    main(*sys.argv)