This document summarizes the research activities of the Berlin Center for Genome Based Bioinformatics at the Technical University of Applied Sciences. The center focuses on modeling and analyzing biochemical systems using Petri nets. Specifically, it has modeled central metabolic pathways like glycolysis and developed Petri net tools to validate biochemical networks and analyze the behavior of large networks like E. coli metabolism.
Multiple Features Based Two-stage Hybrid Classifier Ensembles for Subcellular...CSCJournals
Subcellular localization is a key functional characteristic of proteins. As an interesting ``bio-image informatics\'\' application, an automatic, reliable and efficient prediction system for protein subcellular localization can be used for establishing knowledge of the spatial distribution of proteins within living cells and permits to screen systems for drug discovery or for early diagnosis of a disease. In this paper, we propose a two-stage multiple classifier system to improve classification reliability by introducing rejection option. The system is built as a cascade of two classifier ensembles. The first ensemble consists of set of binary SVMs which generalizes to learn a general classification rule and the second ensemble, which also include three distinct classifiers, focus on the exceptions rejected by the rule. A new way to induce diversity for the classifier ensembles is proposed by designing classifiers that are based on descriptions of different feature patterns. In addition to the Subcellular Location Features (SLF) generally adopted in earlier researches, three well-known texture feature descriptions have been applied to cell phenotype images, which are the local binary patterns (LBP), Gabor filtering and Gray Level Coocurrence Matrix (GLCM). The different texture feature sets can provide sufficient diversity among base classifiers, which is known as a necessary condition for improvement in ensemble performance. Using the public benchmark 2D HeLa cell images, a high classification accuracy 96% is obtained with rejection rate $21\\%$ from the proposed system by taking advantages of the complementary strengths of feature construction and majority-voting based classifiers\' decision fusions.
IMPORTANT: If you want to get a clear review of the Differences & Complementarities Between « Heuristic » and « Mathematical » approaches, we invite you to download our presentation given during the EPA (European Psychiatric Association) conference in 2011 that is now utilized in training programs.
Following the Evolution of New Protein Folds via Protodomains [Report]Spencer Bliven
Protein evolution proceeds through genetic mechanisms, but selection acts on biological assemblies. I define a protodomain as a minimal independently evolving unit with conserved structure. Protodomain rearrangements have minimal impact on biological assemblies, so they represent a valid evolutionary path through fold space.
This report is the written portion of my Candidacy Exam at University of California, San Diego. It discusses my current research in Philip Bourne's lab, as well as proposes research for my thesis over the next two years. Slides for the oral presentation are available at http://www.slideshare.net/sbliven/following-the-evolution-of-new-protein-folds-via-protodomains
Multiple Features Based Two-stage Hybrid Classifier Ensembles for Subcellular...CSCJournals
Subcellular localization is a key functional characteristic of proteins. As an interesting ``bio-image informatics\'\' application, an automatic, reliable and efficient prediction system for protein subcellular localization can be used for establishing knowledge of the spatial distribution of proteins within living cells and permits to screen systems for drug discovery or for early diagnosis of a disease. In this paper, we propose a two-stage multiple classifier system to improve classification reliability by introducing rejection option. The system is built as a cascade of two classifier ensembles. The first ensemble consists of set of binary SVMs which generalizes to learn a general classification rule and the second ensemble, which also include three distinct classifiers, focus on the exceptions rejected by the rule. A new way to induce diversity for the classifier ensembles is proposed by designing classifiers that are based on descriptions of different feature patterns. In addition to the Subcellular Location Features (SLF) generally adopted in earlier researches, three well-known texture feature descriptions have been applied to cell phenotype images, which are the local binary patterns (LBP), Gabor filtering and Gray Level Coocurrence Matrix (GLCM). The different texture feature sets can provide sufficient diversity among base classifiers, which is known as a necessary condition for improvement in ensemble performance. Using the public benchmark 2D HeLa cell images, a high classification accuracy 96% is obtained with rejection rate $21\\%$ from the proposed system by taking advantages of the complementary strengths of feature construction and majority-voting based classifiers\' decision fusions.
IMPORTANT: If you want to get a clear review of the Differences & Complementarities Between « Heuristic » and « Mathematical » approaches, we invite you to download our presentation given during the EPA (European Psychiatric Association) conference in 2011 that is now utilized in training programs.
Following the Evolution of New Protein Folds via Protodomains [Report]Spencer Bliven
Protein evolution proceeds through genetic mechanisms, but selection acts on biological assemblies. I define a protodomain as a minimal independently evolving unit with conserved structure. Protodomain rearrangements have minimal impact on biological assemblies, so they represent a valid evolutionary path through fold space.
This report is the written portion of my Candidacy Exam at University of California, San Diego. It discusses my current research in Philip Bourne's lab, as well as proposes research for my thesis over the next two years. Slides for the oral presentation are available at http://www.slideshare.net/sbliven/following-the-evolution-of-new-protein-folds-via-protodomains
The main objective of this work is to facilitate the identification, sharing, and reasoning about cerebral tumors observations via the formalization of their semantic meanings in order to facilitate their exploitation in both the clinical practice and research. We focused our analysis on the VASARI terminology as a proof of concept, but we are convinced that our work can be useful in other biomedical imaging contexts.
Project report: Investigating the effect of cellular objectives on genome-sca...Jarle Pahr
Report from a half-semester master-level project carried out at the department of biotechnology, Norwegian University of Science and Technology. Describes a MATLAB-based framework for comparing experimental metabolic flux data with model predictions and evaluating objective functions.
Analysis of Neocognitron of Neural Network Method in the String RecognitionIDES Editor
This paper aims that analysing neural network method
in pattern recognition. A neural network is a processing device,
whose design was inspired by the design and functioning of
human brain and their components. The proposed solutions
focus on applying Neocognitron Algorithm model for pattern
recognition. The primary function of which is to retrieve in a
pattern stored in memory, when an incomplete or noisy version
of that pattern is presented. An associative memory is a
storehouse of associated patterns that are encoded in some
form. In auto-association, an input pattern is associated with
itself and the states of input and output units coincide. When
the storehouse is incited with a given distorted or partial
pattern, the associated pattern pair stored in its perfect form
is recalled. Pattern recognition techniques are associated a
symbolic identity with the image of the pattern. This problem
of replication of patterns by machines (computers) involves
the machine printed patterns. There is no idle memory
containing data and programmed, but each neuron is
programmed and continuously active.
Study of Membrane Transport for Protein Filtration Using Artificial Neural Ne...IJERDJOURNAL
ABSTRACT: Artificial Neural Networks (ANNs) are nonlinear mapping structures which functions same as human brain. Modeling can be made stronger especially while the underlying data relationship is not known. ANNs may recognize and learn inter-related patterns between input data sets and related target values. After training, ANNs may be utilized to judge the output of new independent input data. Thus ANNs are used best for the modeling of membrane processes, like ultra filtration and microfiltration. This allows us to judge the permeate flux and membrane rejection as functions of process variables. The aim is modeling of membrane transport for protein filtration is to analyze membrane systems by means of ANNs. To analyze this different ANNs are developed with the help of Mat lab. [1a][9]
And Then Google Declared: "Only Those Who Put in the Hard Work Will Show Up in Search Results"
Optimizing your website for search used to be a task for web developers. But SEO has come a long way in its brief history. All the tricks that once fooled Google will now most likely get you dropped completely off the results pages. The good news is that the tactics that actually work today are things anyone can do. SEO is no longer a mystery—it’s just hard work.
Learn how to do the right work by tuning in to this free archived webinar. Aptera’s Director of Digital Marketing Services Ron Mattocks will share what steps you can take to bring in more traffic than any of your competitors are getting. You’ll learn:
- Why the marketing team should be driving your SEO efforts instead of developers
- The single most important consideration that will influence your SEO performance for better or worse
- Why the steps for building an effective SEO strategy are super easy but no one wants to follow them
- How searching for the SEO silver bullet will only shoot you in the foot
The main objective of this work is to facilitate the identification, sharing, and reasoning about cerebral tumors observations via the formalization of their semantic meanings in order to facilitate their exploitation in both the clinical practice and research. We focused our analysis on the VASARI terminology as a proof of concept, but we are convinced that our work can be useful in other biomedical imaging contexts.
Project report: Investigating the effect of cellular objectives on genome-sca...Jarle Pahr
Report from a half-semester master-level project carried out at the department of biotechnology, Norwegian University of Science and Technology. Describes a MATLAB-based framework for comparing experimental metabolic flux data with model predictions and evaluating objective functions.
Analysis of Neocognitron of Neural Network Method in the String RecognitionIDES Editor
This paper aims that analysing neural network method
in pattern recognition. A neural network is a processing device,
whose design was inspired by the design and functioning of
human brain and their components. The proposed solutions
focus on applying Neocognitron Algorithm model for pattern
recognition. The primary function of which is to retrieve in a
pattern stored in memory, when an incomplete or noisy version
of that pattern is presented. An associative memory is a
storehouse of associated patterns that are encoded in some
form. In auto-association, an input pattern is associated with
itself and the states of input and output units coincide. When
the storehouse is incited with a given distorted or partial
pattern, the associated pattern pair stored in its perfect form
is recalled. Pattern recognition techniques are associated a
symbolic identity with the image of the pattern. This problem
of replication of patterns by machines (computers) involves
the machine printed patterns. There is no idle memory
containing data and programmed, but each neuron is
programmed and continuously active.
Study of Membrane Transport for Protein Filtration Using Artificial Neural Ne...IJERDJOURNAL
ABSTRACT: Artificial Neural Networks (ANNs) are nonlinear mapping structures which functions same as human brain. Modeling can be made stronger especially while the underlying data relationship is not known. ANNs may recognize and learn inter-related patterns between input data sets and related target values. After training, ANNs may be utilized to judge the output of new independent input data. Thus ANNs are used best for the modeling of membrane processes, like ultra filtration and microfiltration. This allows us to judge the permeate flux and membrane rejection as functions of process variables. The aim is modeling of membrane transport for protein filtration is to analyze membrane systems by means of ANNs. To analyze this different ANNs are developed with the help of Mat lab. [1a][9]
And Then Google Declared: "Only Those Who Put in the Hard Work Will Show Up in Search Results"
Optimizing your website for search used to be a task for web developers. But SEO has come a long way in its brief history. All the tricks that once fooled Google will now most likely get you dropped completely off the results pages. The good news is that the tactics that actually work today are things anyone can do. SEO is no longer a mystery—it’s just hard work.
Learn how to do the right work by tuning in to this free archived webinar. Aptera’s Director of Digital Marketing Services Ron Mattocks will share what steps you can take to bring in more traffic than any of your competitors are getting. You’ll learn:
- Why the marketing team should be driving your SEO efforts instead of developers
- The single most important consideration that will influence your SEO performance for better or worse
- Why the steps for building an effective SEO strategy are super easy but no one wants to follow them
- How searching for the SEO silver bullet will only shoot you in the foot
ANALYSIS OF PROTEIN MICROARRAY DATA USING DATA MININGijbbjournal
Latest progress in biology, medical science, bioinformatics, and biotechnology has become important and
tremendous amounts of biodata that demands in-depth analysis. On the other hand, recent progress in data
mining research has led to the development of numerous efficient and scalable methods for mining
interesting patterns in large databases. This paper bridge the two fields, data mining and bioinformatics
for successful mining of biological data. Microarrays constitute a new platform which allows the discovery
and characterization of proteins.
National Resource for Networks Biology's TR&D Theme 3: Although networks have been very useful for representing molecular interactions and mechanisms, network diagrams do not visually resemble the contents of cells. Rather, the cell involves a multi-scale hierarchy of components – proteins are subunits of protein complexes which, in turn, are parts of pathways, biological processes, organelles, cells, tissues, and so on. In this technology research project, we will pursue methods that move Network Biology towards such hierarchical, multi-scale views of cell structure and function.
Unlocking Productivity: Leveraging the Potential of Copilot in Microsoft 365, a presentation by Christoforos Vlachos, Senior Solutions Manager – Modern Workplace, Uni Systems
GraphSummit Singapore | The Art of the Possible with Graph - Q2 2024Neo4j
Neha Bajwa, Vice President of Product Marketing, Neo4j
Join us as we explore breakthrough innovations enabled by interconnected data and AI. Discover firsthand how organizations use relationships in data to uncover contextual insights and solve our most pressing challenges – from optimizing supply chains, detecting fraud, and improving customer experiences to accelerating drug discoveries.
The Art of the Pitch: WordPress Relationships and SalesLaura Byrne
Clients don’t know what they don’t know. What web solutions are right for them? How does WordPress come into the picture? How do you make sure you understand scope and timeline? What do you do if sometime changes?
All these questions and more will be explored as we talk about matching clients’ needs with what your agency offers without pulling teeth or pulling your hair out. Practical tips, and strategies for successful relationship building that leads to closing the deal.
Encryption in Microsoft 365 - ExpertsLive Netherlands 2024Albert Hoitingh
In this session I delve into the encryption technology used in Microsoft 365 and Microsoft Purview. Including the concepts of Customer Key and Double Key Encryption.
Alt. GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using ...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
GDG Cloud Southlake #33: Boule & Rebala: Effective AppSec in SDLC using Deplo...James Anderson
Effective Application Security in Software Delivery lifecycle using Deployment Firewall and DBOM
The modern software delivery process (or the CI/CD process) includes many tools, distributed teams, open-source code, and cloud platforms. Constant focus on speed to release software to market, along with the traditional slow and manual security checks has caused gaps in continuous security as an important piece in the software supply chain. Today organizations feel more susceptible to external and internal cyber threats due to the vast attack surface in their applications supply chain and the lack of end-to-end governance and risk management.
The software team must secure its software delivery process to avoid vulnerability and security breaches. This needs to be achieved with existing tool chains and without extensive rework of the delivery processes. This talk will present strategies and techniques for providing visibility into the true risk of the existing vulnerabilities, preventing the introduction of security issues in the software, resolving vulnerabilities in production environments quickly, and capturing the deployment bill of materials (DBOM).
Speakers:
Bob Boule
Robert Boule is a technology enthusiast with PASSION for technology and making things work along with a knack for helping others understand how things work. He comes with around 20 years of solution engineering experience in application security, software continuous delivery, and SaaS platforms. He is known for his dynamic presentations in CI/CD and application security integrated in software delivery lifecycle.
Gopinath Rebala
Gopinath Rebala is the CTO of OpsMx, where he has overall responsibility for the machine learning and data processing architectures for Secure Software Delivery. Gopi also has a strong connection with our customers, leading design and architecture for strategic implementations. Gopi is a frequent speaker and well-known leader in continuous delivery and integrating security into software delivery.
Sudheer Mechineni, Head of Application Frameworks, Standard Chartered Bank
Discover how Standard Chartered Bank harnessed the power of Neo4j to transform complex data access challenges into a dynamic, scalable graph database solution. This keynote will cover their journey from initial adoption to deploying a fully automated, enterprise-grade causal cluster, highlighting key strategies for modelling organisational changes and ensuring robust disaster recovery. Learn how these innovations have not only enhanced Standard Chartered Bank’s data infrastructure but also positioned them as pioneers in the banking sector’s adoption of graph technology.
Generative AI Deep Dive: Advancing from Proof of Concept to ProductionAggregage
Join Maher Hanafi, VP of Engineering at Betterworks, in this new session where he'll share a practical framework to transform Gen AI prototypes into impactful products! He'll delve into the complexities of data collection and management, model selection and optimization, and ensuring security, scalability, and responsible use.
Why You Should Replace Windows 11 with Nitrux Linux 3.5.0 for enhanced perfor...SOFTTECHHUB
The choice of an operating system plays a pivotal role in shaping our computing experience. For decades, Microsoft's Windows has dominated the market, offering a familiar and widely adopted platform for personal and professional use. However, as technological advancements continue to push the boundaries of innovation, alternative operating systems have emerged, challenging the status quo and offering users a fresh perspective on computing.
One such alternative that has garnered significant attention and acclaim is Nitrux Linux 3.5.0, a sleek, powerful, and user-friendly Linux distribution that promises to redefine the way we interact with our devices. With its focus on performance, security, and customization, Nitrux Linux presents a compelling case for those seeking to break free from the constraints of proprietary software and embrace the freedom and flexibility of open-source computing.
zkStudyClub - Reef: Fast Succinct Non-Interactive Zero-Knowledge Regex ProofsAlex Pruden
This paper presents Reef, a system for generating publicly verifiable succinct non-interactive zero-knowledge proofs that a committed document matches or does not match a regular expression. We describe applications such as proving the strength of passwords, the provenance of email despite redactions, the validity of oblivious DNS queries, and the existence of mutations in DNA. Reef supports the Perl Compatible Regular Expression syntax, including wildcards, alternation, ranges, capture groups, Kleene star, negations, and lookarounds. Reef introduces a new type of automata, Skipping Alternating Finite Automata (SAFA), that skips irrelevant parts of a document when producing proofs without undermining soundness, and instantiates SAFA with a lookup argument. Our experimental evaluation confirms that Reef can generate proofs for documents with 32M characters; the proofs are small and cheap to verify (under a second).
Paper: https://eprint.iacr.org/2023/1886
Removing Uninteresting Bytes in Software FuzzingAftab Hussain
Imagine a world where software fuzzing, the process of mutating bytes in test seeds to uncover hidden and erroneous program behaviors, becomes faster and more effective. A lot depends on the initial seeds, which can significantly dictate the trajectory of a fuzzing campaign, particularly in terms of how long it takes to uncover interesting behaviour in your code. We introduce DIAR, a technique designed to speedup fuzzing campaigns by pinpointing and eliminating those uninteresting bytes in the seeds. Picture this: instead of wasting valuable resources on meaningless mutations in large, bloated seeds, DIAR removes the unnecessary bytes, streamlining the entire process.
In this work, we equipped AFL, a popular fuzzer, with DIAR and examined two critical Linux libraries -- Libxml's xmllint, a tool for parsing xml documents, and Binutil's readelf, an essential debugging and security analysis command-line tool used to display detailed information about ELF (Executable and Linkable Format). Our preliminary results show that AFL+DIAR does not only discover new paths more quickly but also achieves higher coverage overall. This work thus showcases how starting with lean and optimized seeds can lead to faster, more comprehensive fuzzing campaigns -- and DIAR helps you find such seeds.
- These are slides of the talk given at IEEE International Conference on Software Testing Verification and Validation Workshop, ICSTW 2022.
LF Energy Webinar: Electrical Grid Modelling and Simulation Through PowSyBl -...DanBrown980551
Do you want to learn how to model and simulate an electrical network from scratch in under an hour?
Then welcome to this PowSyBl workshop, hosted by Rte, the French Transmission System Operator (TSO)!
During the webinar, you will discover the PowSyBl ecosystem as well as handle and study an electrical network through an interactive Python notebook.
PowSyBl is an open source project hosted by LF Energy, which offers a comprehensive set of features for electrical grid modelling and simulation. Among other advanced features, PowSyBl provides:
- A fully editable and extendable library for grid component modelling;
- Visualization tools to display your network;
- Grid simulation tools, such as power flows, security analyses (with or without remedial actions) and sensitivity analyses;
The framework is mostly written in Java, with a Python binding so that Python developers can access PowSyBl functionalities as well.
What you will learn during the webinar:
- For beginners: discover PowSyBl's functionalities through a quick general presentation and the notebook, without needing any expert coding skills;
- For advanced developers: master the skills to efficiently apply PowSyBl functionalities to your real-world scenarios.
Securing your Kubernetes cluster_ a step-by-step guide to success !KatiaHIMEUR1
Today, after several years of existence, an extremely active community and an ultra-dynamic ecosystem, Kubernetes has established itself as the de facto standard in container orchestration. Thanks to a wide range of managed services, it has never been so easy to set up a ready-to-use Kubernetes cluster.
However, this ease of use means that the subject of security in Kubernetes is often left for later, or even neglected. This exposes companies to significant risks.
In this talk, I'll show you step-by-step how to secure your Kubernetes cluster for greater peace of mind and reliability.
Maruthi Prithivirajan, Head of ASEAN & IN Solution Architecture, Neo4j
Get an inside look at the latest Neo4j innovations that enable relationship-driven intelligence at scale. Learn more about the newest cloud integrations and product enhancements that make Neo4j an essential choice for developers building apps with interconnected data and generative AI.
Observability Concepts EVERY Developer Should Know -- DeveloperWeek Europe.pdfPaige Cruz
Monitoring and observability aren’t traditionally found in software curriculums and many of us cobble this knowledge together from whatever vendor or ecosystem we were first introduced to and whatever is a part of your current company’s observability stack.
While the dev and ops silo continues to crumble….many organizations still relegate monitoring & observability as the purview of ops, infra and SRE teams. This is a mistake - achieving a highly observable system requires collaboration up and down the stack.
I, a former op, would like to extend an invitation to all application developers to join the observability party will share these foundational concepts to build on:
Free Complete Python - A step towards Data Science
Berlin center for genome based bioinformatics koch05
1. Berlin Center for Genome Based Bioinformatics
Bioinformatics, Technical University of Applied Sciences
TFH BIOINFORMATICS
Head
Ina Koch (since 04/2002)
Technical University of Applied Sciences
Seestr. 64
D – 13347 Berlin
Phone: ++49-(0)30-4504 3972
Fax: ++49-(0)30-4504 3959
Email: ina.koch@tfh-berlin.de
http://www.tfh-berlin.de/bi/
Team
Karsten Wenzel (technician, 0.5 position, since
01/2003)
Stefan Bartel (student)
Andrea Sackmann (student, 11/2004-02/2005) Ralf Mehle (student, 04/2003 -08/2003,
Sabrina Hoffmann (student, 04/2004-07/2004) 10/2003-12/2003, 10/2004-10/2004)
Thomas Runge (student, 02/2004-07/2004) Patrick May (student, 10/2002-01/2003)
RESEARCH DIRECTION 43
The main goal of the BMBF funding was to es- are divided into special metabolisms or path-
tablish a master’s course in bioinformatics for ways, which often correspond to special main
graduates in biological, and medical fields. This functions of the cell, e.g. carbon metabolism,
has been done very successfully. Moreover, it energy metabolism, purine metabolism, glyco-
was also possible to follow research work at TFH. lytic pathway, and many others. Due to newly
developed techniques in experimental biology,
Due to the former working field of the head of
as microarray analysis, a huge amount of data
the group two main research directions were pur-
of biological processes has been produced over
sued in the last years, the modelling and analy-
the last years.
sis of biochemical systems and the theoretical
analysis of protein structures (see publication To handle the arising data amount it is necessa-
list). Following the valuable and constructive ry to represent and store them computationally
advices of the Scientific Advisory Board of BCB using a unique description of biochemical path-
the group has focused its work on the first topic ways. There are several special databases of
with a main emphasis in modelling medically pathway or interaction data. All of them use dif-
relevant systems. The group has made a large ferent description techniques. The most com-
contribution for establishing Petri net based tools monly used database, containing many path-
in systems biology. ways of different species, is the KEGG Database,
but its representation of concurrently behaving
pathways by monochromatic graphs is not free
Modelling and analysis of of ambiguities.
biochemical systems
Biochemical pathways are modelled at different
Similar to computer scientists, biologists use “di- abstraction levels. It must be distinguished be-
vide and conquer”-techniques to investigate sub- tween quantitative (kinetic) models and qualita-
systems experimentally. Processes in the cell tive (stoichiometric or even purely causal) mod-
2. Berlin Center for Genome Based Bioinformatics
Scientific Report 2005
els. The first ones represent the actual objective As a common intermediate representation we
and real purpose in the long-term. The aim of have used Petri nets. They provide a mathemati-
these models is to predict the system’s dynam- cally unique representation of biochemical path-
ics. Related evaluation methods are typically ways, whereby different biochemical processes
based on solutions of systems of ordinary differ- may be depicted hierarchically at different ab-
ential equations. Contrary, qualitative models are straction levels. Moreover, established Petri net
commonly used only, if kinetic parameters are analysis techniques can be used for the valida-
not available or incomplete. All these qualitative tion of qualitative biochemical models, before
models are based on more or less graph-theo- they are extended to quantitative ones. Alto-
retical descriptions of the system topology, which gether, Petri nets enjoy the following features
are defined in case of stoichiometric models by which might be of great help for systems biol-
the known stoichiometric equations. ogy: (1) readability - to support understanding,
(2) execution (animation techniques) - to expe-
Model validation of biochemi- rience a model in order to get really familiar with
it, (3) validation techniques - for consistency
cal networks applying Petri
checks to ensure the model integrity and corre-
nets spondence to reality, and (4) analysis techniques
With the increasing number of known metabo- - for qualitative as well as quantitative behaviour
lites and known interactions between them, vali- prediction.
dation of the interaction network becomes more
We started the application of Petri nets to bio-
and more important. The net behaviour is no
chemical systems with well investigated systems
more understandable and predictable by using
as the glycolysis and pentose phosphate path-
human skills only, but available evaluation pack-
way in erythrocytes and could confirm the text-
ages for quantitative models are not able to
book knowledge for these systems. We have
check the model for validity. There is a strong
used different Petri nets techniques as coloured
demand for mathematical methods to validate a
44 model for consistency and to answer questions
Petri nets (see Runge T, Methodik zur Model-
lierung und Validierung von biochemischen Netz-
on general structural and dynamic properties as
werken mit gefärbten Petrinetzen, dargestellt am
liveness, dead states, traps, structural deadlocks,
Beispiel der Glykolyse (diploma thesis) and the
and invariant properties. Moreover, existing
papers presented at CPN Conferences at Uni-
methods are dedicated to a certain system type
versity Aarhus (Denmark). To analyse much
or a certain pathway represented by special
larger networks we started to model the whole
graphs. Hence, a crucial point seems to be the
E.coli metabolism (see Kramer N, Modelling and
concise and unambiguous representation of bio-
analysis of biological processes using Petri net
logical networks to handle computationally these
theory (master thesis). The results show the
highly integrated networks in an efficient man-
modelling and analysis power of Petri nets, but
ner. For that purpose, a readable language with
also the limits of currently existing tools. From
an unambiguous semantics would be of great
this work many suggestions arise for further de-
help as a common intermediate language to
velopments of Petri net theory.
avoid the production of just larger patchwork, ex-
posed to even more interpretation choices. In-
dependently of the given description level and Analysis of metabolic
the particular view extension, all pathways ex- networks
hibit inherently very complex structures, exploit- In order to prove the modelling and analysis
ing all the patterns well-known in software engi- power we have applied Petri net methods in
neering as sequence, branching, repetition, and strong co-operation to the experimentally groups
concurrency, in any combination. But opposite to other systems, which are of great interest and
to technical networks, natural networks tend to where parts of the behaviour are unknown.
be much more complex and apparently unstruc-
tured, making the comprehensibility of the full Thus, we have modelled and analysed the main
network of interactions extremely difficult and carbon metabolism in Solanum tuberosum (po-
therefore error-prone. tato) tuber in co-operation with the Max Planck
Institute for Plant Physiology Golm and BTU
3. Berlin Center for Genome Based Bioinformatics
Bioinformatics, Technical University of Applied Sciences
Cottbus. We have provided an approach for Analysis of gene regulatory
model validation of metabolic networks using networks
Petri net theory, which we demonstrate for the
sucrose breakdown pathway in the potato tuber. The understanding of gene regulatory networks
We have started with a hierarchical modelling of is essential for understanding cell processes. A
the metabolic network as a Petri net and contin- project has recently been started in co-opera-
ued with the analysis of qualitative properties of tion with the Friedrich Schiller-University Jena.
the network. The results characterise the net It aims at modelling the splicing processes in
structure and give insight into complex net Drosophila melanogaster. The processes are
behaviour. One important technique is the cal- well-characterised, but wide-spread in the litera-
culation of the T-invariants as well as P-invari- ture. The Petri net model reflects the interac-
ants of a system. The T-invariants reflect the tions between metabolic components, signal
main processes taking place in the metabolic transduction paths, and gene regulatory pro-
system in reality. P-invariants reflect substance cesses at mRNA level. This work is embedded
conservations. The presented detailed discus- in other investigations concerning alternative
sion of occurring T-invariants explains the net splicing and is the first approach for modelling
behaviour as possible combinations of subpath- such kind of network with Petri nets or qualita-
ways, which reflect correctly experimentally tive analysis methods.
known results. In the future, the existing net
should be extended by other central metabolic Application of Petri nets to
processes (e.g. glycolysis, respiration, amino medically relevant systems
acid metabolism) to get a deeper insight into the An important aspect of our work caused by strong
whole metabolism in the potato tuber. co-operations with medical research institutes as
Charité and MDC concerns systems of medical
Analysis of interest. Thus, we have analysed the blood
signal transduction pathways clutting process (see Neumann G, Modellierung
biochemischer Abläufe mit Petri-Netzen -
45
The first signal transduction pathway we mod- Hämostase vs. Fibrinolyse vs. Inhibitoren (di-
elled represents the basic processes of apoptosis ploma thesis) in co-operation with physicians to
in mammalian cells. Apoptosis is an essential yield a valid very large and complex model con-
part of normal physiology for most metazoan taining many hierarchy levels, which should also
species. Disturbances in the apoptotic process be used in medical research.
can lead to several diseases. The signal trans-
duction pathway of apoptosis includes highly In co-operation with clinical groups at Charité, a
complex mechanisms to control and execute project headed by Astrid Speer of the TFH, the
programmed cell death. The results provide a Duchenne muscle Dystrophy is modelled. This
mathematically unique and valid model enabling project started recently and is of great interest,
the confirmation of known properties as well as also because theoretical and experimental work
new insights in this pathway. This work will be influences each other. The application of other
continued to refine the model and to analyse also bioinformatics methods already lead to a publi-
quantitative aspects. cation.
Another recent work is a diploma thesis on mod- During a PhD thesis the liver cell metabolism
elling of the interactions in and between the sig- was modelled by differential equations and as
nal transduction pathways in Saccharomyces Petri net (with MDC and BTU). Another recently
cerevisiae (yeast). In the BCB group of Edda started project concerns the modelling of G1/S-
Klipp at MPIMG the same pathway is modelled phase in mammalian cells.
using different methods. Both diploma students
are in contact with each other. Besides a deeper Implementation of tools for
understanding of these pathways one aim is the analysing biochemical
detailed comparison of both methods in order to systems
see the differences and to check the possibility
We have developed two new tools as help in
of a combination of parts of both approaches.
analysing biochemical systems. One is a simple
4. Berlin Center for Genome Based Bioinformatics
Scientific Report 2005
path-search tool, which allows searching for all Other scientific activities of
paths in a biochemical network using a special the group
constraint language. This tool is based on the
bachelor thesis of Markus Schüler, and is us- Group members are active as referees for sci-
able under http://www.sanaga.de/~stepp. entific journals as Bioinformatics, Journal of
Theoretical Biology, In Silico Biology, Protein
The second tool, which has been developed by Engineering, BioSystems, and for conferences
Albert Gevorgyan, represents a complex and as RECOMB 2002, CMSB 2003, ISMB 2005.
advanced Petri net editor, which allows the con- They are members of the scientific program com-
version of KEGG networks into Petri net models mittee for CMSB 2003 and ISMB 2005.
with integrated Petri net analysis techniques and
an underlying relational data base system to Based on his master’s thesis Systematische
store and search other information as kinetic data Analyse von RNA-Strukturen mit bioinformati-
or literature data. In co-operation with Hiroyuki schen Methoden zur Vorhersage von Antisense-
Ogata of the Jean-Michel Claverie group at Cen- Oligodesoxyribonukleotiden Christian Köberle in
tre National de la Recherche Scientifique (CNRS) co-operation with Max Planck Institute for Infec-
in Marseille, France this tool shall be combined tion Biology founded the company Nucleic Acid
with their own databases. Design, which designs siRNA structures for func-
tional studies.
Theoretical analysis of The quality of the scientific work is reflected by
the accepted tutorial on “Qualitative Modelling
protein structures
and Analysis of Biochemical Pathways with Petri
In the post-genomic research protein structures Nets” given at ICSB 2004 at Heidelberg and the
and their functions play a crucial role. To handle many invited talks given, e.g. at Second Bertinoro
the large and complex structure data of proteins Computational Biology Meeting, Bertinoro (Italy),
computationally unique descriptions and nota- Dagstuhl-Seminar “Integrative Bioinformatics -
46 tions at different abstraction levels are neces-
sary. To define a unique language for protein
Aspects of the Virtual Cell”, “Conference BioCon
Valley Life Science for the Future”, and various
topologies we have developed four linear nota- European universities.
tions based on a graph-theoretical description
In the future the group wants to combine meth-
of protein secondary structure topology (see fig-
ods for qualitative analysis with those for quanti-
ure).
tative analysis to provide practicable tools for the
To search for protein topologies we have imple- scientific community. Other tasks will be the con-
mented a web-based database Protein Topol- nection of net analysis tools with expression data
ogy Graph Library (PTGL), which contains over and the further development of existing models
15.000 protein structure topologies (http:// in co-operation with experimentally working
sanaga.tfh-berlin.de/~ptgl/ptgl.html). groups.
PTGL is applied in the threading algorithm de-
veloped in the BCB group of Thomas Steinke at
Zuse Institute Berlin. Other co-operations exist
with Davis Gilbert of the University of Glasgow.
Left: Structure of the protein 1G3E. Center: Key notation of the folding graph B of 1G3E. Right: The reduced of
the folding graph B of 1G3E.
5. Berlin Center for Genome Based Bioinformatics
Bioinformatics, Technical University of Applied Sciences
Relevant former
Teaching Publications Scientific Output*
The group is heavily involved in Heiner M, Koch I & Voss K Publications
teaching. Per scientist the teach- (2001). Analysis and Simulation Koch I, Schüler M & Heiner M
ing load ranges from 12 to 16 of Steady States in Metabolic (2005). A Software Tool for Petri
hours per week in each semes- Pathways with Petri Nets. In: Net based based Analysis in Bio-
ter in the accredited MSc course CPN'01-Third Workshop and chemical Networks. In Silico Bi-
in bioinformatics. Moreover, the Tutorial on Practical Use of ology (accepted)
group leads the whole course and Coloured Petri Nets and the CPN
is responsible for its realisation. Tools, University of Aarhus, Den- Heiner M & Koch I (2004). Petri
mark, Jensen K, ed., 15-34 Net Based Model Validation in
The lectures given by the scien- Systems Biology. In: Proceed-
(ISSN 0105-8517)
tist of the group are focused on ings 25th International Confer-
foundations in computer science, Sunyaev S, Ramensky V, Koch ence on Application and Theory
on object-oriented programming I, Lathe III W, Kondrashov AS & of Petri Nets, ICATPN 2004, Bo-
in Java, on bioinformatics algo- Bork P (2001). Prediction of Del- logna, Italy, LCNS 3099, Springer
rithms for theoretical sequence eterious Human Alleles. Hum Verlag, Berlin, 216-237
and structure analysis, and on an Mol Genetics "bf 10"(6): 591-597
introduction into Petri net theory Heiner M, Koch I & Will J (2004).
Koch I (2001). Fundamental Model Validation of Biological
and their applications for model-
Study: Enumerating all con- Pathways Using Petri Nets -
ling and analysis of biochemical
nected maximal common sub- Demonstrated for Apoptosis. J
systems. One module is variable
graphs in two graphs. Theoreti- BioSystems 75(1-3):15-28
for new topics in which industry
cal Computer Science 250:1-30
or research institutes are espe- Koch I, Junker BH & Heiner M
cially interested. This year in this Schuster S, Pfeiffer T, Molden- (2004). Application of Petri net
module molecular modelling and hauer F, Koch I & Dandekar T theory for modelling and valida-
statistical applications in medicine (2000). Structural Analysis of tion of the sucrose breakdown
will be taught. metabolic Networks: Elementary
Flux Modes, Analogy to Petri
pathway in the potato tuber. 47
All lectures are regularly evalu- Bioinformatics (in press)
Nets, and Application to Myco-
ated and have reached top scor- May P, Barthel S & Koch I
plasma pneumoniae. In: Proc
ing positions within the university. (2004). PTGL - Protein Topology
Germ Conf Bioinf, Bauer EB,
Rost U, Stoye J, Vingron M, eds., Graph Library. Bioinformatics
Logos Verlag Berlin,115-120 20(17):3277-3279
(ISBN 3-89722-498-4) Popova-Zeugmann L, Heiner M
Koch I, Schuster S & Heiner M & Koch I (2004). Modelling and
(2000). Using time-dependent Analysis of Biochemical Net-
Petri nets for the analysis of works with Time Petri Nets. In:
metabolic networks. Workshop Proc Workshop Concurrency,
Modellierung und Simulation Specification & Programming,
Metabolischer Netzwerke, Hofe- Informatik-Berichte der HUB
städt R, Lautenbach K, Lange M, 170(1), Caputh, 136-143 (ISSN
eds., Preprint No.10, Faculty of 0863-095X)
Computer Science, Otto-von- Rother K, Müller H, Trissl S,
Guericke University, Magde- Koch I, Steinke T, Preissner R,
burg, 15-21 Frömmel C & Leser U (2004).
Columba: Multidimensional Data
Integration of Protein Annota-
tions. In: Rahm E, ed., Data In-
tegration in the Life Sciences,
Lecture Notes in Computer Sci-
ence 2994, Springer, Leipzig,
Germany:156-171
* BCB members are marked bold.
6. Berlin Center for Genome Based Bioinformatics
Scientific Report 2005
Runge T (2004). Qualitative Path Patents / Spin off Reilich, Michael: Simulation
Analysis of Metabolic Pathways Steinbeis Transferzentrum Nu- neuronaler Vorgänge in Säugern,
Using Petri Nets for Generic Mod- cleic Acids Design (STZ-NAD), Diploma thesis in Technical Com-
elling. Technical Report BTU founded in May 2004 by Volker puter Science, Charité and Tech-
Cottbus I-03/2004 (ISSN 1437- Patzel and Christian Köberle nical University of Applied Sci-
7969) ences 2004
Runge T (2004). Application of Schelbert, Christian: Structural
Coloured Petri Nets in Systems Student Theses Aspects of Alternative Splicing
Biology. In: Proc 5th Workshop Effinger, Daniel & Rolschews- using Bioinformatical Methods,
CPN, University of Aarhus, 77-95 ki, Johann: Development of a Master Thesis, Technical Univer-
dynamic web application: an in- sity of Applied Sciences 2004
Kriventseva EV, Koch I, App-
weiler R, Vingron M, Bork P, formation system for pest man- Schramm, Gerrit: MAT - Micro
Gelfand MS & Sunyaev S (2003). agement, Master Thesis, Tech- Array Analysis Tool, Master The-
Increase of functional diversity by nical University of Applied Sci- sis, Max Delbrück Center for
alternative splicing. Trends in ences 2004 Molecular Medicine (MDC) and
Genetics 19:124-128 Huber, Florian: Classification of Technical University of Applied
EST-tissue information using a Sciences 2004
Sifringer M, Uhlenberg B, Lam-
mel S, Hanke R, Neumann B, von directed acyclic graph, Master Waldminghaus, Torsten: In
Moers A, Koch I & Speer A Thesis, Max Delbrück Center for silico analysis and selection of
(2003). Identification of trans- Molecular Medicine (MDC) and RNA secondary structures, Mas-
cripts from a subtraction library Technical University of Applied ter Thesis, Technical University
which might be responsible for Sciences 2004 of Applied Sciences 2004 (in co-
the mild phenotype in an intra- Kramer, Nina: Modelling and operation with the MPI for Infec-
familially variable course of Du- analysis of biological processes tion Biology, Berlin)
48 chenne muscular dystrophy. Hu-
man Mol Genetics 114:149-156
using Petri net theory, Master
Thesis, Technical University of
Hettling, Johannes: Ein
automatischer Vergleich zwi-
Voss K, Heiner M & Koch I Applied Sciences Berlin and BTU schen der Protein Topology
(2003). Steady State Analysis of Cottbus 2004 Graph Library und SCOP, Bach-
Metabolic Pathways using Petri Neumann, Gerry: Modellierung elor Thesis, Free University of
Nets. In Silico Biol 3(3):367-387 biochemischer Abläufe mit Petri- Berlin 2004 (in cooperation with
Netzen - Hämostase vs. Fibrino- TFH Berlin, supervisor: I. Koch)
Boué S, Vingron M, Kriventseva
E & Koch I (2002). Theoretical lyse vs. Inhibitoren, Diploma the- Schüler, Markus: Graphen-
analysis of alternative splice sis in Computer Science, BTU theoretische Weganalyse in
forms using computational meth- Cottbus and Technical University biochemischen Netzwerken mit
ods. Bioinformatics 18(Suppl 2), of Applied Sciences Berlin EPNPSearch, Bachelor Thesis,
T. Lengauer, H.-P. Lenhof, eds. Cottbus 2004 Free University of Berlin 2004 (in
Runge, Thomas: Methodik zur cooperation with TFH Berlin, Su-
Schuster S, Pfeiffer T, Koch I,
Modellierung und Validierung von pervisor: I. Koch)
Moldenhauer F & Dandekar T
(2002). Exploring the pathway biochemischen Netzwerken mit Barthel, Stefan: Eine Schnitt-
structure of metabolism: decom- gefärbten Petrinetzen, dargestellt stelle zur Visualisierung daten-
position into subnetworks and am Beispiel der Glykolyse, Di- bankbasierter Proteinstruktur-
application to Mycoplasma ploma thesis in Computer Sci- topologien, Diploma Thesis in
pneumoniae. Bioinformatics ence, BTU Cottbus and Techni- Computer Science, Technical
18(2):351-361 cal University of Applied Sci- University of Applied Sciences
ences 2004 Berlin 08/2003 (supervisor: I.
Koch)
7. Berlin Center for Genome Based Bioinformatics
Bioinformatics, Technical University of Applied Sciences
Böhme, Ulrike: Vorhersage re- Schirmer, Markus: Homology
levanter Methylierungsorte für die Modelling of selected kinase do-
Regulation der Genaktivität, Mas- mains, Master Thesis, Schering
ters Thesis, Max Delbrück Cen- AG and Technical University of
ter for Molecular Medicine (MDC) Applied Sciences 2003
and Technical University of Ap-
Tillack, Thorsten: Entwicklung
plied Sciences 2003
einer Datenbankanwendung für
Bortfeld, Ralf: Conception and molekularbiologische Daten über
implementation of a MySQL Alternatives Spleißen, Diploma
based analysis environment for Thesis in Computer Science,
tissue alternative splicing, Mas- Technical University of Applied
ter Thesis, Max Delbrück Centre Sciences Berlin 01/2003
for Molecular Medicine (MDC)
Boué Stéphanié: Computatio-
and Technical University of Ap-
nal investigation of alternative
plied Sciences, Berlin 2003 (su-
splicing, Master Thesis, Max
pervisor: H. Pospisil, MDC, I.
Planck Institute for Molecular
Koch, TFH)
Genetics 2002
Djoko, Djoko: Theoretische
Untersuchungen zu Cytochrom
P-450 Enzymen mit Methoden Co-operations
der Bioinformatik, Master Thesis, Monika Heiner, Brandenburgi-
Technical University of Berlin and sche Technische Universität TU
Technical University of Applied Cottbus
Sciences, Berlin 2003 (supervi-
sor: L.-A. Garbe, TUB, I. Koch, Ursula Egner, Schering AG
TFH) Denis Thieffry, Claudine Chaoui- 49
Doudieu, Octave Marie Noubi- ya, Mediterranean University
bou: Using sequence informa- Marseille
tion in protein docking proce- Volker Patzel, Max Planck Insti-
dures, Master Thesis, European tute for Infection Biology, Berlin
Media Laboratory Heidelberg
Hiroyuko Ogata, Jean-Michel
(EML) and Technical University
Claverie, CNRS Marseille
of Applied Sciences 2003
Falk Schreiber, Björn Junker, IPK
Köberle, Christian: Systemati-
Gatersleben
sche Analyse von RNA-Struk-
turen mit bioinformatischen Me- Claudia Täubner, TU Braun-
thoden zur Vorhersage von Anti- schweig
sense-Oligodesoxyribonukleo-
Heike Pospisil, MDC Berlin
tiden, Master Thesis, Technical
University of Applied Sciences, Thomas Steinke, ZIB
Berlin 2003 (supervisor: V. Ulf Leser, Institute of Computer
Patzel, MPI-IB, I. Koch, TFH) Science, HUB
May, Patrick: Erstellung einer Cornelius Frömmel, Charité
Online-DB für Proteintopologien
auf der Grundlage eines Edda Klipp, Rainer Spang, Max
graphentheoretischen Algorith- Planck Institute for Molecular
mus, Master Thesis, Technical Genetics
University of Applied Sciences,
Berlin 03/2003
8. Berlin Center for Genome Based Bioinformatics
Scientific Report 2005
50