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  <front>
    <journal-meta />
    <article-meta>
      <title-group>
        <article-title>When Process Mining Meets Bioinformatics</article-title>
      </title-group>
      <contrib-group>
        <contrib contrib-type="author">
          <string-name>R.P. Jagadeesh Chandra Bose</string-name>
          <xref ref-type="aff" rid="aff1">1</xref>
          <xref ref-type="aff" rid="aff2">2</xref>
        </contrib>
        <contrib contrib-type="author">
          <string-name>Wil M.P. van der Aalst</string-name>
          <email>w.m.p.v.d.aalstg@tue.nl</email>
          <xref ref-type="aff" rid="aff1">1</xref>
        </contrib>
        <aff id="aff0">
          <label>0</label>
          <institution>6</institution>
          ,
          <addr-line>Best</addr-line>
          ,
          <country country="NL">The Netherlands</country>
        </aff>
        <aff id="aff1">
          <label>1</label>
          <institution>Department of Mathematics and Computer Science, University of Technology</institution>
          ,
          <addr-line>Eindhoven</addr-line>
          ,
          <country country="NL">The Netherlands</country>
        </aff>
        <aff id="aff2">
          <label>2</label>
          <institution>Philips Healthcare</institution>
          ,
          <addr-line>Veenpluis 5</addr-line>
        </aff>
      </contrib-group>
      <fpage>147</fpage>
      <lpage>154</lpage>
      <abstract>
        <p>Process mining techniques can be used to extract non-trivial process related knowledge and thus generate interesting insights from event logs. Similarly, bioinformatics aims at increasing the understanding of biological processes through the analysis of information associated with biological molecules. Techniques developed in both disciplines can bene t from one another, e.g., sequence analysis is a fundamental aspect in both process mining and bioinformatics. In this paper, we draw a parallel between bioinformatics and process mining. In particular, we present some initial success stories that demonstrate that the emerging process mining discipline can bene t from techniques developed for bioinformatics.</p>
      </abstract>
      <kwd-group>
        <kwd>sequence</kwd>
        <kwd>trace</kwd>
        <kwd>execution patterns</kwd>
        <kwd>diagnostics</kwd>
        <kwd>conformance</kwd>
        <kwd>alignment</kwd>
        <kwd>con guration</kwd>
      </kwd-group>
    </article-meta>
  </front>
  <body>
    <sec id="sec-1">
      <title>Introduction</title>
      <p>
        Bioinformatics aims at increasing the understanding of biological processes and
entails the application of computational techniques to understand and organize
the information associated with biological macromolecules [
        <xref ref-type="bibr" rid="ref1">1</xref>
        ]. Sequence analysis
or sequence informatics is a core aspect of bioinformatics that is concerned with
the analysis of DNA/protein sequences3 and has been an active area of research
for over four decades.
      </p>
      <p>
        Process mining is a relatively young research discipline aimed at discovering,
monitoring and improving real processes by extracting knowledge from event
logs readily available in today's information systems [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. Business processes leave
trails in a variety of data sources (e.g., audit trails, databases, transaction logs).
Hence, every process instance can be described by a trace, i.e., a sequence of
events. Process mining techniques are able to extract knowledge from such traces
and provide a welcome extension to the repertoire of business process analysis
techniques. The topics in process mining can be broadly classi ed into three
3 DNA stores information in the form of the base nucleotide sequence, which is a string
of four letters (A, T, G and C) while protein sequences are sequences de ned over
twenty amino acids and are the fundamental determinants of biological structure
and function.
categories (i) discovery, (ii) conformance, and (iii) enhancement. Process
discovery deals with the discovery of models from event logs. For example, there
are dozens of techniques that automatically construct process models (e.g., Petri
nets or BPMN models) from event logs [
        <xref ref-type="bibr" rid="ref2">2</xref>
        ]. Discovery is not restricted to
controlow; one may also discover organizational models, etc. Conformance deals with
comparing an apriori model with the observed behavior as recorded in the log
and aims at detecting inconsistencies/deviations between a process model and
its corresponding execution log. In other words, it checks for any violation
between what was expected to happen and what actually happened. Enhancement
deals with extending or improving an existing model based on information about
the process execution in an event log. For example, annotating a process model
with performance data to show bottlenecks, throughput times etc. Some of the
challenges in process mining include the discovery of process maps (navigable
hierarchical process models) and the provision of process diagnostics support for
auditors and analysts [
        <xref ref-type="bibr" rid="ref3">3</xref>
        ].
      </p>
      <p>It is important to note that, to a large extent, sequence analysis is a
fundamental aspect in almost all facets of process mining and bioinformatics. In spite
of all the peculiarities speci c to business processes and process mining, the
relatively young eld of process mining should, in our view, take account of the
conceptual foundations, practical experiences, and analysis tools developed by
sequence informatics researchers over the last couple of decades. In this paper, we
describe some of the analogies between problems studied in both disciplines. We
present some initial successes which demonstrate that process mining techniques
can bene t from such a cross-fertilization.
2</p>
    </sec>
    <sec id="sec-2">
      <title>Notations</title>
      <p>We use the following notations in this paper.</p>
      <p>{ Let denote the set of activities. + is the set of all non-empty nite
sequences of activities from .
{ A trace corresponds to a process instance expressed as a nite sequence of
activities. T 2 + is a trace over . jT j denotes the length of the trace T .
{ The ordered sequence of activities in T is denoted as T (1)T (2)T (3) : : : T (n)
where T (k) represents the kth activity in the trace.</p>
      <p>{ An event log, L, corresponds to a multi-set (or bag) of traces from +.
3</p>
    </sec>
    <sec id="sec-3">
      <title>From Sequence to Structure</title>
      <p>
        A DNA sequence motif is de ned as a nucleic acid sequence pattern that has
some biological signi cance (both structural and functional) [
        <xref ref-type="bibr" rid="ref4">4</xref>
        ]. These motifs
are usually found to recur in di erent genes or within a single gene. For example,
tandem repeats (tandemly repeating DNA) are associated with various regulatory
mechanisms such as protein binding [
        <xref ref-type="bibr" rid="ref5">5</xref>
        ]. More often than not, sequence motifs
are also associated with structural motifs found in proteins thus establishing a
strong correspondence between sequence and structure.
      </p>
      <p>
        Likewise, common subsequences of activities in an event log that are found
to recur within a process instance or across process instances have some domain
(functional) signi cance. In [
        <xref ref-type="bibr" rid="ref6">6</xref>
        ], we adopted the sequence patterns (e.g., tandem
repeats, maximal repeats etc.) proposed in the bioinformatics literature,
correlated them to commonly used process model constructs (e.g., tandem repeats
and tandem arrays correspond to simple loop constructs) and proposed a means
to form abstractions over these patterns. Using these abstractions as a basis, we
proposed a two-phase approach to process discovery [
        <xref ref-type="bibr" rid="ref7">7</xref>
        ]. The rst phase comprises
of pre-processing the event log with abstractions at a desired level of
granularity and the second phase deals with discovering the process maps with seamless
zoom-in/out facility. Figure 1 summarizes the overall approach.
pattern
trace
macro
structure
micro
structures
relationships
between
patterns
common
execution
patterns
event logs
      </p>
      <p>Figure 2 highlights the di erence between the traditional approach to
process discovery and the two-phase approach. Note that the process model (map)
discovered using the two-phase approach is simpler. Our approach supports the
abstraction of activities based on their context and type, and provides a seamless
zoom-in and zoom-out functionality.</p>
      <p>Thus the bringing together of concepts in bioinformatics to process mining
has enabled the discovery of hierarchical process models and opened a new
perspective in dealing with ne granular event logs.</p>
      <p>Event Log
s a m b c u d n j e
s a m q f h l l h g i k e
s a m f g h l h i k q e
s a m b c d n u j e
s a m f h l g i h l h k q e
s a m q f g i h l h k e
s a m q f g h l h i k e
s a m p c u d n r e
s a m b d n c u j e
s a m p d n c u r e</p>
      <p>Two-phase</p>
      <p>Approach
Abstractions de ned over
common execution patterns</p>
      <p>Traditional
Approach
Transformed
Log
X b Z j e
X q Y Y e
X Y Y q e
X b Z Z j e
X Y Y Y q e
X q Y Y Y e
X q Y Y Y e
X p Z r e
X b Z j e</p>
      <p>X p Z r e</p>
    </sec>
    <sec id="sec-4">
      <title>Sequence Alignment and Process Diagnostics</title>
      <p>
        Multiple sequence alignment has been a subject of extensive research in
computational biology for over three decades. Sequence alignment is an essential tool in
bioinformatics that assists in unraveling the secondary and tertiary structures
of proteins and molecules, their evolution and functions, and in inferring the
taxonomic, phylogenetic or cladistic relationships between organisms, diagnoses
of genetic diseases etc [
        <xref ref-type="bibr" rid="ref8 ref9">8, 9</xref>
        ].
      </p>
      <p>
        In [
        <xref ref-type="bibr" rid="ref10">10</xref>
        ], we have adapted sequence alignment to traces in an event log and
showed that it carries signi cant promise in process diagnostics. The goal of
trace alignment is to align traces in such a way that event logs can be easily
explored. Given a set of traces T = fT1; T2; : : : ; Tng, trace alignment can be
de ned as a mapping of T to another set of traces T = fT1; T2; : : : ; Tng where
Ti 2 ( [ f g)+ for 1 i n. In addition, the following three properties need
to be satis ed with respect to T and T: (a) each trace in T is of the same length
i.e., there exists an m 2 N such that jT1j = jT2j = = jTnj = m (b) Ti is equal
to Ti after removing all gap symbols ` ' and (c) there is no k 2 f1; : : : ; mg such
that 81 i n Ti(k) = .
      </p>
      <p>Trace alignment can be used to explore the process in the early stages of
analysis and to answer speci c questions in later stages of analysis. More speci cally,
trace alignment can assist in answering questions such as:
{ What is the most common (likely) process behavior that is executed?
{ Where do my process instances deviate and what do they have in common?
{ Are there any common patterns of execution in my traces?
{ What are the contexts in which an activity or a set of activities is executed
in my event log?
{ What are the process instances that share/capture a desired behavior either
exactly or approximately?
{ Are there particular patterns (e.g., milestones, concurrent activities etc.) in
my process?
Figure 3 depicts the results of trace alignment for a real-life log from a rental
agency. The gure shows that trace alignment can assist in answering a variety
of diagnostic questions. Every row corresponds to a process instance and time
increases from left to right. The horizonal position is based on logical time rather
than real timestamps. If two rows have the same activity name in the same
column, then the corresponding two events are very similar and are therefore
aligned. Note that the same activity can appear in multiple columns. By reading
a row from left to right, we can see the sequence of activities (i.e., the trace) that
was executed for a process instance. Process instances having the same trace can
be grouped into one row to simplify the diagram. The challenge is to nd an
alignment that is as simple and informative as possible. For example, the number
of columns and gaps should be minimized while having as much consensus as
possible per column.</p>
      <p>The application of sequence alignment in bioinformatics to process mining
has created an altogether new dimension to conformance checking; deviations
and violations are uncovered by analyzing just the raw event traces (thereby
avoiding the need for process models).</p>
      <p>
        Finding good quality alignments is notoriously complex. The initial results of
trace alignment are de nitely encouraging. Nonetheless, there are various new
challenges when adopting biological sequence alignment to trace alignment in
the context of business processes [
        <xref ref-type="bibr" rid="ref11">11</xref>
        ]. For example, biological sequences tend to
be homogenous whereas traces in semi-structured processes (e.g., care processes
in hospitals) tend to be much more variable. Other di erences are the fact that
traces in an event log can be of very di erent lengths (e.g., due to loops) and
may be the result of concurrency. These characteristics provide new challenges
for sequence alignment.
5
      </p>
    </sec>
    <sec id="sec-5">
      <title>Phylogeny and Process Con guration</title>
      <p>
        Phylogenetics refers to the study of evolutionary relationships, and is one of the
rst applications in bioinformatics. A phylogeny is a tree representation of the
evolutionary history of a set (family) of organisms, gene/protein sequences etc.
The basic premise in phylogenetics is that genes have evolved by duplication
and divergence from common ancestors [
        <xref ref-type="bibr" rid="ref12">12</xref>
        ]. The genes can therefore exist in a
nested hierarchy of relatedness.
      </p>
      <p>
        In the past couple of years, process con guration has gained prominence in
the BPM community [
        <xref ref-type="bibr" rid="ref13">13</xref>
        ]. Process con guration is primarily concerned with
managing families of business processes that are similar to one another in many
ways yet di ering in some other ways. For example, processes within di erent
municipalities are very similar in many aspects and di er in some other aspects.
Such discrepancies can arise due to characteristics peculiar to each municipality
Common execution patterns are
captured in the form of well
conserved regions
Concurrent activities manifest in
mutually exclusive traces across
di erent columns
The consensus sequence represents
the backbone of the process
      </p>
      <p>
        Deviations, exceptional behavior and rare event
executions are captured in regions that are
sparsely lled i.e., regions with lots of gap
symbol `-' or in regions that are well conserved with a
few rare gaps.
(e.g., di erences in size, demographics, problems, and policies) that need to
be maintained. Furthermore, operational processes need to change to adapt to
changing circumstances, e.g., new legislation, extreme variations in supply and
demand, seasonal e ects, etc. A con gurable process model describes a family
of similar process models in a given domain [
        <xref ref-type="bibr" rid="ref13">13</xref>
        ], and can be thought of as
the genesis (root) of the family. All variants in the family can be derived from
the con gurable model through a series of change patterns [
        <xref ref-type="bibr" rid="ref14">14</xref>
        ]. One of the core
research problems in process con guration is to automatically derive con gurable
process models from speci c models and event logs.
      </p>
      <p>One can nd stark similarity between phylogenetics and process con
guration. Techniques have been proposed in the bioinformatics literature to discover
phylogenies both from (protein) structure as well as from sequences. This can be
compared to deriving con gurable process models from speci c models and from
event logs respectively. The adaptability of phylogeny construction techniques
to process con guration needs to be explored.</p>
      <p>
        Techniques from bioinformatics have also been adopted to trace clustering in
process mining [
        <xref ref-type="bibr" rid="ref15 ref16">15, 16</xref>
        ]. Sequence clustering techniques have been applied to deal
with unlabeled event logs4 in process mining [
        <xref ref-type="bibr" rid="ref17">17</xref>
        ]. Experiences from
bioinformatics can also contribute to tooling and infrastructure e orts in process mining.
For example, visualization is one of the challenging problems in process mining
tooling5. A lot of current visualization means in process mining become
unmanageable when dealing with large event logs thereby compromising the
comprehensibility. Visualization is used in many areas within bioinformatics (e.g.,
sequence matching, genome browsing, multiple sequence alignment etc.), with
varying success, and good tools already exist. As another example, to cater to the
rapidly increasing accumulation of biological data, lots of e orts had been
initiated in bioinformatics to create advanced databases with analysis capabilities
devoted to particular categories e.g., Genbank (cataloguing DNA data),
SWISSPROT/TrEMBL (repository of protein sequences) etc. Recently, similar e orts
had been initiated in the process modeling and process mining community to
create repositories with advanced support for dealing with process model
collections e.g., APROMORE [
        <xref ref-type="bibr" rid="ref18">18</xref>
        ]. Such an overlap between the goals combined with
the promising initial results calls for a more rigorous attempt at understanding
and exploiting the synergy between these two disciplines.
6
      </p>
    </sec>
    <sec id="sec-6">
      <title>Conclusions</title>
      <p>Bioinformatics and process mining share some common goals. In this paper, we
presented the commonalities between the problems and techniques studied in
bioinformatics and process mining. Exploiting these commonalities, we
demonstrated that process mining can bene t from the plethora of techniques developed
in bioinformatics. Initial attempts at such a crossover have enabled the discovery
of hierarchical process models and helped extending the scope of conformance
checking to also cover the direct inspection of traces. Although this is just a
rst step towards an interaction between the two disciplines, the results are very
promising and the relationship will be explored further in our future work.
Acknowledgments The authors are grateful to Philips Healthcare for funding
the research in process mining.
4 In an unlabeled event log, the case to which an event belongs to is unknown.
5 ProM is an extensible framework that provides a comprehensive set of
tools/plugins for the discovery and analysis of process models from event logs. See
http://www.processmining.org for more information and to download ProM.</p>
    </sec>
  </body>
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