A Programming and Simulation Environment for Population Dynamics Adam Spiro and Ehud Shapiro*

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A Programming and Simulation Environment for Population Dynamics Adam Spiro and Ehud Shapiro*

Spiro and Shapiro BMC Bioinformatics (2016) 17:303 DOI 10.1186/s12859-016-1155-x ERRATUM Open Access Erratum to: eSTGt: a programming and simulation environment for population dynamics Adam Spiro and Ehud Shapiro* Erratum After publication of the original article [1] it was brought to our attention that important information was missing from the Acknowledgments. The completed Acknowledgments section should read as follows: Acknowledgements We thank Tamir Biezuner for performing the ex vivo experiment and helping to calibrate the simulation parameters. We also thank Shalev Itzkovitz for raising potential simulation scenarios, Yoni Herzog for user feedback and beta testing, and our various collaborators for useful discussions regarding possible biological scenarios. We would also like to thank the anonymous reviewers for their constructive comments. This research was supported by the following foundations: The European Union FP7-ERC-AdG (233047), The EU-H2020- ERC- AdG (670535), The DFG (611042), The Israeli Science Foundation (ISF, P14587), The ISF-BROAD (P15439), The NIH (VUMC 38347) and The Kenneth and Sally Leafman Appelbaum Discovery Fund. Ehud Shapiro is the Incumbent of The Harry Weinrebe Professorial Chair of Computer Science and Biology. Reference 1. Spiro and Shapiro: eSTGt: a programming and simulation environment for population dynamics. BMC Bioinformatics 2016, 17:187 10.1186/s12859-016-1004-y Submit your next manuscript to BioMed Central and we will help you at every step: • We accept pre-submission inquiries • Our selector tool helps you to ﬁnd the most relevant journal • We provide round the clock customer support • Convenient online submission • Thorough peer review • Inclusion in PubMed and all major indexing services • Maximum visibility for your research * Correspondence: [email protected] Submit your manuscript at Department of Computer Science and Applied Mathematics and Department www.biomedcentral.com/submit of Biological Chemistry, Weizmann Institute of Science, Rehovot, Israel © 2016 The Author(s). Open Access This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated..

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Biography – Dr. Ehud Shapiro Function Professor of Computer Science and Biology, Weizmann Institute of Science, Israel Educati
Biography – Dr. Ehud Shapiro Function Professor of Computer Science and Biology, Weizmann Institute of Science, Israel Education & Professional Born in Jerusalem in 1955, Ehud Shapiro was awarded a B.A./B.Sc. Background degree with distinction in Mathematics and Philosophy from Tel Aviv University in 1979, and a Ph.D. in Computer Science from Yale Univer- sity in 1982. His doctoral studies with Prof. Dana Angluin attempted to provide an algorithmic interpretation to the noted philosopher of science Karl Popper's approach to scientific discovery. Joining the Weizmann Institute’s Department of Computer Science and Applied Mathematics in 1982 as a postdoctoral fellow, Prof. Shapiro was inspired by the Japanese Fifth Generation Computer Systems project to invent a high- level programming language for parallel and distributed computer sys- tems, named Concurrent Prolog. In 1993, Prof. Shapiro took a leave of absence from the Weizmann Institute to found and serve as CEO of Ubique Ltd., an Israeli Internet software pioneer. Prof. Shapiro returned to the Weizmann Institute in August 1998, where he is now an associate professor in the Depart- ments of Computer Science and Applied Mathematics, and Biological Chemistry, and incumbent of the Harry Weinrebe Chair of Computer Science and Biology. Preparing for his return to academia, Prof. Shapiro ventured into study of molecular biology. Initially curious about the origins of life, he was sidetracked into attempting to build a computer from biological mole- cules, guided by a vision of "A Doctor in a Cell": a biomolecular com- puter that operates inside the living body, programmed with medical knowledge to diagnose diseases and produce the requisite drugs.
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From Fifth Generation Computing to Skill Science
New Generation Computing (2019) 37:141–158 https://doi.org/10.1007/s00354-019-00058-y From Fifth Generation Computing to Skill Science A Biographical Essay of Koichi Furukawa Tomonobu Ozaki1 · Randy Goebel2 · Katsumi Inoue3,4,5 Received: 7 February 2019 / Accepted: 10 April 2019 / Published online: 25 April 2019 © The Author(s) 2019 Abstract Professor Koichi Furukawa, an eminent computer scientist and former Editor-in- Chief of the New Generation Computing journal, passed away on January 31, 2017. His passing was a surprise, and we were all shocked and saddened by the news. To remember the deceased, this article reviews the great career and contributions of Professor Koichi Furukawa, focusing on his research activities on the foundation and application of logic programming. Professor Furukawa had both a deep understand- ing and broad impact on logic programming, and he was always gentle but persistent in articulating its value across a broad spectrum of computer science and artifcial intelligence research. This article introduces his research along with its insightful and unique philosophical framework. Keywords Institute for New Generation Computer Technology · Logic programming · Inductive logic programming · Skill science * Tomonobu Ozaki [email protected] Randy Goebel [email protected] Katsumi Inoue [email protected] 1 College of Humanities and Sciences, Nihon University, Tokyo, Japan 2 Department of Computing Science, University of Alberta, Edmonton, Canada 3 National Institute of Informatics, Tokyo, Japan 4 Department of Informatics, SOKENDAI (The Graduate University for Advanced Studies), Tokyo, Japan 5 Department of Computer Science, School of Computing, Tokyo Institute of Technology, Tokyo, Japan Vol.:(0123456789)123 142 New Generation Computing (2019) 37:141–158 Fig.
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Lineage Trees Reveal Cells' Histories 23 February 2012
Lineage trees reveal cells' histories 23 February 2012 In recent years, a number of controversial claims comparing a number of genetic sequences called have been made about the female mammal's egg microsatellites - areas where mutations occur like supply - that it is renewed over her adult lifetime clockwork - they can place cells on trees to reveal (as opposed to the conventional understanding their developmental history. that she is born with all of her eggs), and that the source of these eggs is stem cells that originate in A number of papers published by Shapiro, his team the bone marrow. Now, Weizmann Institute and collaborators in recent months have scientists have disproved one of those claims and demonstrated the power and versatility of this pointed in new directions toward resolving the method. One study, for instance, lent support to the other. Their findings, based on an original method notion that the adult stem cells residing in tiny for reconstructing lineage trees for cells, were crypts in the lining of the colon do not harbor, as published online today in PLoS Genetics. thought, "immortal DNA strands." Immortal strands may be retained by dividing stem cells if they The method, developed over several years in the always relegate the newly-synthesized DNA to the lab of Prof. Ehud Shapiro of the Institute's differentiating daughter cell and keep the original Biological Chemistry, and Computer Science and stand in the one that remains a stem cell. Applied Mathematics Departments, uses mutations in specific genetic markers to determine which A second study addressed an open question about cells are most closely related and how far back developing muscle cells.
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Features Special News Feature Synthetic biologists are designing genetic circuits of increasing complexity. But how did the field get to this point, and where is it going? Nathan Blow examines the challenges, and potential applications, of engineering gene circuits. According to Jim Collins, a synthetic engineer wiring a light switch in a house. that such toggles could find use in gene biologist at Boston University who is In 2000, Collins and Gardner’s forward therapy and biotechnology applications exploring the use of transcription factors as engineering efforts paid off, resulting in the future. As it turns out, in hindsight key components in synthetic gene circuits, in a publication in Nature detailing the though, moving from this E. coli toggle bioengineers come in two flavors. construction of a genetic toggle switch in toward more complex circuitry introduces “In their youth, those that take things Escherichia coli, the first synthetic, bistable new problems and challenges — as well as apart become systems biologists, while gene-regulatory network to be described. possibilities. those that put things together and tinker That same issue of Nature also featured a A genetic circuit needs a couple basic go into synthetic biology.” Collins finds report by Michael Elowitz and Stanislas components to function properly. First, himself in the latter class. Leibler describing a synthetic oscillating there needs to be a sensor module capable of A physicist by training, Collins was led gene network in E. coli that periodically identifying a specific input. From there, the somewhat inadvertently into the world of induced synthesis of green fluorescent sensor needs to be connected to a computa- synthetic biology by his BU colleagues.
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Stochastic Computing with Biomolecular Automata
Stochastic computing with biomolecular automata Rivka Adar*†, Yaakov Benenson*†‡, Gregory Linshiz*‡, Amit Rosner§, Naftali Tishby§¶, and Ehud Shapiro*‡ʈ Departments of *Biological Chemistry and ‡Computer Science and Applied Mathematics, Weizmann Institute of Science, Rehovot 76100, Israel; §School of Computer Science and Engineering and ¶Center for Neural Computation, Hebrew University, Jerusalem 91904, Israel Edited by Richard M. Karp, International Computer Science Institute, Berkeley, CA, and approved May 5, 2004 (received for review February 2, 2004) Stochastic computing has a broad range of applications, yet elec- automata the input is encoded as a single DNA molecule, transition tronic computers realize its basic step, stochastic choice between rules are encoded by another set of DNA molecules, and the alternative computation paths, in a cumbersome way. Biomolec- hardware consists of DNA-manipulating enzymes. A computation ular computers use a different computational paradigm and hence commences when all molecular components are present in solution afford novel designs. We constructed a stochastic molecular au- and processes the input molecule in steps performed by the tomaton in which stochastic choice is realized by means of com- hardware molecules, as directed by the software molecules. The petition between alternative biochemical pathways, and choice output molecule, formed by the programmed digestion of the input probabilities are programmed by the relative molar concentrations molecule, encodes the result of the computation. of the software molecules coding for the alternatives. Program- Although these experimental realizations demonstrate pri- mable and autonomous stochastic molecular automata have been marily deterministic computations, both the mathematical no- shown to perform direct analysis of disease-related molecular tion of automata (28) and its molecular realizations afford a indicators in vitro and may have the potential to provide in situ stochastic extension by allowing multiple competing transitions medical diagnosis and cure.
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Ehud Shapiro Molecules and Rivka Adar Kobi Benenson computation Gregory Linshitz Aviv Regev William Silverman Department of Biological Chemistry and Department of Computer Science and Applied Mathematics Tel. 972 8 934 4506 Fax. 972 8 934 4484 E-mail: [email protected] Computing with molucles some are designated accepting states. Its software consists Devices that convert information from one form into another of transition rules, each specifying a next state based on the according to a definite procedure are known as automata. current state and the current symbol. It is initially positioned on One such hypothetical device is the universal Turing machine, the leftmost input symbol in the initial state. In each transition which stimulated work leading to the development of modern the machine moves one symbol to the right, changing its computers. The Turing machine and its special cases, including internal state according to one of the applicable transition rules. finite automata, operate by scanning a data tape, whose Alternatively, it may suspend without completing the computation striking analogy to information-encoding biopolymers inspired if no transition rule applies. A computation terminates upon several designs for molecular DNA computers. Laboratory-scale processing the last input symbol. An automaton is said to accept computing using DNA and human-assisted protocols has been an input if a computation on this input terminates in an accepting demonstrated, but the attempts to realize computing devices final state. Our molecular finite automaton has two states and it operates on binary strings of symbols. It solves computational problems autonomously. The automaton’s hardware consists of a restriction nuclease and ligase, the software and input are encoded by double-stranded DNA, and programming amounts to choosing appropriate software molecules.
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Lecture Notes in Computer Science
Lecture Notes in Computer Science Edited by G. Goos and J. Hartmanis 225 Third International Conference on Logic Programming Imperial College of Science and Technology, London, United Kingdom, July 14-18, 1986 Proceedings Edited by Ehud Shapiro # Springer-Verlag Berlin Heidelberg NewYork London Paris Tokyo Editorial Board D. Barstow W. Brauer P. Brinch Hansen D. Gries D. Luckham C. Moler A. Pnueli G. Seegm~iller J. Stoer N. Wirth Editor Ehud Shapiro Department of Computer Science The Weizmann Institute of Science Rehovot 76100, Israel CR Subject Classifications (1985): D.1, D.3, F.1, F.3, 1.2 ISBN 3-540-16492-8 Springer-Verlag Berlin Heidelberg New York ISBN 0-387-16492-8 Springer-Verlag New York Heidelberg Berlin Library of Congress Cataloging-in-Publication Data. International Conference on Logic Program- ming (3rd: 1986: Imperial College of Science and Technology, London, England). Third Internatio- nal Conference on Logic Programming, Imperial College of Science and Technology, London, United Kingdom. (Lecture notes in computer science; 225)Includes bibliographies. 1. Logic programming-Congresses. I. Shapiro, Ehud Y. II. Title. II1. Series. QA76.6.15466 1986 005.1 86-13477 ISBN 0-38"7-16492-8 (U.S.) This work is subject to copyright. All rights are reserved, whether the whole or part of the material is concerned, specifically those of translation, reprinting, re-use of illustrations, broadcasting, reproduction by photocopying machine or similar means, and storage in data banks. Under § 54 of the German Copyright Law where copies are made for other than private use, a fee is payable to "Verwertungsgesellschaft Wort", Munich.
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On the Journey from Nematode to Human, Scientists Dive by the Zebrafish Cell Lineage Tree Ehud Shapiro
Shapiro Genome Biology (2018) 19:63 https://doi.org/10.1186/s13059-018-1453-x RESEARCH HIGHLIGHT Open Access On the journey from nematode to human, scientists dive by the zebrafish cell lineage tree Ehud Shapiro no further information on the nature of the cells, and hence Abstract rather uninformative. To label the tree with cell types, tran- Three recent single-cell papers use novel CRISPR-Cas9- scriptomic (or other) analysis of each cell is needed in sgRNA genome editing methods to shed light on the addition to its genomic analysis. While single-cell tran- zebrafish cell lineage tree. scriptomicsisprogressinginleapsandboundsandisnow the cornerstone technology of the international Human Cell Atlas project, integrated single-cell genome and tran- Whole-organism cell lineage tree scriptome analysis is still in its infancy [2]. The cell lineage tree of the nematode Caenorhabditis Fortunately, a new idea has recently emerged. It is pos- elegans was uncovered four decades ago by painstaking sible to use CRISPR-Cas9-sgRNA genome editing to ad- ’ observation of the nematodes development. The tree, typ- dress these two problems simultaneously. In accordance ically drawn upside-down, has the root at the top, repre- with the multiple discovery theory, the idea is presented in senting the fertilized zygote, the leaves at the bottom, three independent, almost simultaneous, publications, all ’ representing the organisms extant cells, and internal applying it to the discovery of the zebrafish cell lineage branches representing past cells that have divided. Cell tree [3–5]. lineage trees are typically labeled with the types of the cells Uncovering zebrafish cell lineages by scarring its gen- and, in the case of the small (959 somatic cells) and deter- ome, waiting, then fishing the scars, the method uses ministic cell lineage tree of C.
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Cells As Computation
concepts Cells as computation Cellular abstractions Aviv Regev and Ehud Shapiro an essential property of the phenomenon; computable, bringing to bear computational lthough we are successfully consolidat- knowledge about the mathematical represen- Computer science could provide the ing our knowledge of the ‘sequence’ and tation; understandable, offering a conceptual abstraction needed for consolidating A‘structure’ branches of molecular cell framework for thinking about the scientific biology in an accessible manner, the moun- domain; and extensible, allowing the capture knowledge of biomolecular systems. tains of knowledge about the function, activi- of additional real properties in the same ty and interaction of molecular systems in mathematical framework. Using this abstraction opens up new possi- cells remain fragmented. Sequence and struc- For example, the DNA-as-string abstrac- bilities for understanding molecular systems. ture research use computers and computer- tion is relevant in capturing the primary For example, computer science distinguishes ized databases to share, compare, criticize sequence of nucleotides without including between two levels to describe a system’s and correct scientific knowledge, to reach a higher- and lower-order biochemical proper- behaviour: implementation (how the system consensus quickly and effectively. Why can’t ties; it allows the application of a battery of is built, say the wires in a circuit) and specifica- the study of biomolecular systems make a string algorithms, including probabilistic tion
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Biomolecular Computers with Multiple Restriction Enzymes
Genetics and Molecular Biology, 40, 4, 860-870 (2017) Copyright © 2017, Sociedade Brasileira de Genética. Printed in Brazil DOI: http://dx.doi.org/10.1590/1678-4685-GMB-2016-0132 Research Article Biomolecular computers with multiple restriction enzymes Sebastian Sakowski1, Tadeusz Krasinski1, Jacek Waldmajer2, Joanna Sarnik3, Janusz Blasiak3 and Tomasz Poplawski3 1Faculty of Mathematics and Computer Science, University of Lodz, Lodz, Poland. 2Logic, Language and Information Group, Department of Philosophy, University of Opole, Opole, Poland. 3Department of Molecular Genetics, University of Lodz, Lodz, Poland. Abstract The development of conventional, silicon-based computers has several limitations, including some related to the Heisenberg uncertainty principle and the von Neumann “bottleneck”. Biomolecular computers based on DNA and proteins are largely free of these disadvantages and, along with quantum computers, are reasonable alternatives to their conventional counterparts in some applications. The idea of a DNA computer proposed by Ehud Shapiro’s group at the Weizmann Institute of Science was developed using one restriction enzyme as hardware and DNA frag- ments (the transition molecules) as software and input/output signals. This computer represented a two-state two-symbol finite automaton that was subsequently extended by using two restriction enzymes. In this paper, we pro- pose the idea of a multistate biomolecular computer with multiple commercially available restriction enzymes as hardware. Additionally, an algorithmic method for the construction of transition molecules in the DNA computer based on the use of multiple restriction enzymes is presented. We use this method to construct multistate, biomolecular, nondeterministic finite automata with four commercially available restriction enzymes as hardware. We also describe an experimental applicaton of this theoretical model to a biomolecular finite automaton made of four endonucleases.
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AI Magazine Volume 9 Number 1 (1988) (© AAAI) WORKSHOP REPORT Concurrent Logic Program- ming, Metaprogramming, and Open Systems Kenneth M. Kahn he workshop began with the and how can the agent deal with An informal workshop on concurrent T visions of concurrent logic pro- "breakdown" in the sense discussed by logic programming, metaprogramming, gramming and open systems that are Terry Winograd and Fernando Flores. and open systems was held at Xerox Palo driving research at Weizmann, ICOT, Carl Hewitt of MIT presented actors Alto Research Center (PARC) on 8-9 CMU, MIT, and Xerox PARC. A as an alternative computational September 1987 with support from the shared vision emerged from the morn- model for open-system programming. American Association for Artificial Intel- ing session with concurrent logic pro- Many were surprised at the close cor- ligence. The 50 workshop participants came from gramming fulfilling the same role that respondence between the actor model the Japanese Fifth Generation Project C and Assembler do now. Languages and concurrent logic programming. (ICOT), the Weizmann Institute of Sci- such as Flat Concurrent Prolog and This similarity has become increas- ence in Israel, Imperial College in Lon- Guarded Horn Clauses are seen as ingly apparent to researchers in both don, the Swedish Institute of Computer general-purpose, parallel machine lan- fields. Both present a scalable, compu- Science, Stanford University, the Mas- guages and interface languages tational model with fine-grained, sachusetts Institute of Technology (MIT), between hardware and software and implicit concurrency and explicit syn- Carnegie-Mellon University (CMU), Cal not, as a newcomer to this field might chronization control.
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