Optimal selection of epitopes for TXP-immunoaffinity mass spectrometry

<p>Abstract</p> <p>Background</p> <p>Mass spectrometry (MS) based protein profiling has become one of the key technologies in biomedical research and biomarker discovery. One bottleneck in MS-based protein analysis is sample preparation and an efficient fractionation step to reduce the complexity of the biological samples, which are too complex to be analyzed directly with MS. Sample preparation strategies that reduce the complexity of tryptic digests by using immunoaffinity based methods have shown to lead to a substantial increase in throughput and sensitivity in the proteomic mass spectrometry approach. The limitation of using such immunoaffinity-based approaches is the availability of the appropriate peptide specific capture antibodies. Recent developments in these approaches, where subsets of peptides with short identical terminal sequences can be enriched using antibodies directed against short terminal epitopes, promise a significant gain in efficiency.</p> <p>Results</p> <p>We show that the minimal set of terminal epitopes for the coverage of a target protein list can be found by the formulation as a set cover problem, preceded by a filtering pipeline for the exclusion of peptides and target epitopes with undesirable properties.</p> <p>Conclusions</p> <p>For small datasets (a few hundred proteins) it is possible to solve the problem to optimality with moderate computational effort using commercial or free solvers. Larger datasets, like full proteomes require the use of heuristics.</p

Computational Molecular Biology

Computational Biology is a fairly new subject that arose in response to the computational problems posed by the analysis and the processing of biomolecular sequence and structure data. The field was initiated in the late 60's and early 70's largely by pioneers working in the life sciences. Physicists and mathematicians entered the field in the 70's and 80's, while Computer Science became involved with the new biological problems in the late 1980's. Computational problems have gained further importance in molecular biology through the various genome projects which produce enormous amounts of data. For this bibliography we focus on those areas of computational molecular biology that involve discrete algorithms or discrete optimization. We thus neglect several other areas of computational molecular biology, like most of the literature on the protein folding problem, as well as databases for molecular and genetic data, and genetic mapping algorithms. Due to the availability of review papers and a bibliography this bibliography

Streaming beyond sketching for Maximum Directed Cut

We give an $\widetilde{O}(\sqrt{n})$-space single-pass $0.483$-approximation streaming algorithm for estimating the maximum directed cut size ($\textsf{Max-DICUT}$) in a directed graph on $n$ vertices. This improves over an $O(\log n)$-space $4/9 < 0.45$ approximation algorithm due to Chou, Golovnev, Velusamy (FOCS 2020), which was known to be optimal for $o(\sqrt{n})$-space algorithms. $\textsf{Max-DICUT}$ is a special case of a constraint satisfaction problem (CSP). In this broader context, our work gives the first CSP for which algorithms with $\widetilde{O}(\sqrt{n})$ space can provably outperform $o(\sqrt{n})$-space algorithms on general instances. Previously, this was shown in the restricted case of bounded-degree graphs in a previous work of the authors (SODA 2023). Prior to that work, the only algorithms for any CSP were based on generalizations of the $O(\log n)$-space algorithm for $\textsf{Max-DICUT}$, and were in particular so-called "sketching" algorithms. In this work, we demonstrate that more sophisticated streaming algorithms can outperform these algorithms even on general instances. Our algorithm constructs a "snapshot" of the graph and then applies a result of Feige and Jozeph (Algorithmica, 2015) to approximately estimate the $\textsf{Max-DICUT}$ value from this snapshot. Constructing this snapshot is easy for bounded-degree graphs and the main contribution of our work is to construct this snapshot in the general setting. This involves some delicate sampling methods as well as a host of "continuity" results on the $\textsf{Max-DICUT}$ behaviour in graphs.Comment: 57 pages, 2 figure

Algorithmic Solutions for Combinatorial Problems in Resource Management of Manufacturing Environments

This thesis studies the use of heuristic algorithms in a number of combinatorial problems that occur in various resource constrained environments. Such problems occur, for example, in manufacturing, where a restricted number of resources (tools, machines, feeder slots) are needed to perform some operations. Many of these problems turn out to be computationally intractable, and heuristic algorithms are used to provide efficient, yet sub-optimal solutions. The main goal of the present study is to build upon existing methods to create new heuristics that provide improved solutions for some of these problems. All of these problems occur in practice, and one of the motivations of our study was the request for improvements from industrial sources. We approach three different resource constrained problems. The first is the tool switching and loading problem, and occurs especially in the assembly of printed circuit boards. This problem has to be solved when an efficient, yet small primary storage is used to access resources (tools) from a less efficient (but unlimited) secondary storage area. We study various forms of the problem and provide improved heuristics for its solution. Second, the nozzle assignment problem is concerned with selecting a suitable set of vacuum nozzles for the arms of a robotic assembly machine. It turns out that this is a specialized formulation of the MINMAX resource allocation formulation of the apportionment problem and it can be solved efficiently and optimally. We construct an exact algorithm specialized for the nozzle selection and provide a proof of its optimality. Third, the problem of feeder assignment and component tape construction occurs when electronic components are inserted and certain component types cause tape movement delays that can significantly impact the efficiency of printed circuit board assembly. Here, careful selection of component slots in the feeder improves the tape movement speed. We provide a formal proof that this problem is of the same complexity as the turnpike problem (a well studied geometric optimization problem), and provide a heuristic algorithm for this problem.Siirretty Doriast

Self-Evaluation Applied Mathematics 2003-2008 University of Twente

This report contains the self-study for the research assessment of the Department of Applied Mathematics (AM) of the Faculty of Electrical Engineering, Mathematics and Computer Science (EEMCS) at the University of Twente (UT). The report provides the information for the Research Assessment Committee for Applied Mathematics, dealing with mathematical sciences at the three universities of technology in the Netherlands. It describes the state of affairs pertaining to the period 1 January 2003 to 31 December 2008

Äriprotsessimudelite ühildamine

Väitekirja elektrooniline versioon ei sisalda publikatsioone.Ettevõtted, kellel on aastatepikkune kogemus äriprotsesside haldamises, omavad sageli protsesside repositooriumeid, mis võivad endas sisaldada sadu või isegi tuhandeid äriprotsessimudeleid. Need mudelid pärinevad erinevatest allikatest ja need on loonud ning neid on muutnud erinevad osapooled, kellel on erinevad modelleerimise oskused ning praktikad. üheks sagedaseks praktikaks on uute mudelite loomine, kasutades olemasolevaid mudeleid, kopeerides neist fragmente ning neid seejärel muutes. See omakorda loob olukorra, kus protsessimudelite repositoorium sisaldab mudeleid, milles on identseid mudeli fragmente, mis viitavad samale alamprotsessile. Kui sellised fragmendid jätta konsolideerimata, siis võib see põhjustada repositooriumis ebakõlasid -- üks ja sama alamprotsess võib olla erinevates protsessides erinevalt kirjeldatud. Sageli on ettevõtetel mudelid, millel on sarnased eesmärgid, kuid mis on mõeldud erinevate klientide, toodete, äriüksuste või geograafiliste regioonide jaoks. Näiteks on äriprotsessid kodukindlustuse ja autokindlustuse jaoks sama ärilise eesmärgiga. Loomulikult sisaldavad nende protsesside mudelid mitmeid identseid alamfragmente (nagu näiteks poliisi andmete kontrollimine), samas on need protsessid mitmes punktis erinevad. Nende protsesside eraldi haldamine on ebaefektiivne ning tekitab liiasusi. Doktoritöös otsisime vastust küsimusele: kuidas identifitseerida protsessimudelite repositooriumis korduvaid mudelite fragmente, ning üldisemalt -- kuidas leida ning konsolideerida sarnasusi suurtes äriprotsessimudelite repositooriumites? Doktoritöös on sisse toodud kaks üksteist täiendavat meetodit äriprotsessimudelite konsolideerimiseks, täpsemalt protsessimudelite ühildamine üheks mudeliks ning mudelifragmentide ekstraktimine. Esimene neist võtab sisendiks kaks või enam protsessimudelit ning konstrueerib neist ühe konsolideeritud protsessimudeli, mis sisaldab kõikide sisendmudelite käitumist. Selline lähenemine võimaldab analüütikutel hallata korraga tervet perekonda sarnaseid mudeleid ning neid muuta sünkroniseeritud viisil. Teine lähenemine, alamprotsesside ekstraktimine, sisaldab endas sagedasti esinevate fragmentide identifitseerimist (protsessimudelites kloonide leidmist) ning nende kapseldamist alamprotsessideks

Combinatorial optimization for affinity proteomics

Biochemical test development can significantly benefit from combinatorial optimization. Multiplex assays do require complex planning decisions during implementation and subsequent validation. Due to the increasing complexity of setups and the limited resources, the need to work efficiently is a key element for the success of biochemical research and test development. The first approached problem was to systemically pool samples in order to create a multi-positive control sample. We could show that pooled samples exhibit a predictable serological profile and by using this prediction a pooled sample with the desired property. For serological assay validation it must be shown that the low, medium, and high levels can be reliably measured. It is shown how to optimally choose a few samples to achieve this requirements. Finally the latter methods were merged to validate multiplexed assays using a set of pooled samples. A novel algorithm combining fast enumeration and a set cover formulation has been introduced. The major part of the thesis deals with optimization and data analysis for Triple X Proteomics - immunoaffinity assays using antibodies binding short linear, terminal epitopes of peptides. It has been shown that the problem of choosing a minimal set of epitopes for TXP setups, which combine mass spectrometry with immunoaffinity enrichment, is equivalent to the well-known set cover problem. TXP Sandwich immunoassays capture and detect peptides by combining the C-terminal and N-terminal binders. A greedy heuristic and a meta-heuristic using local search is presented, which proves to be more efficient than pure ILP formulations. All models were implemented in the novel Java framework SCPSolver, which is applicable to many problems that can be formulated as integer programs. While the main design goal of the software was usability, it also provides a basic modelling language, easy deployment and platform independence. One question arising when analyzing TXP data was: How likely is it to observe multiple peptides sharing the same terminus? The algorithms TXP-TEA and MATERICS were able to identify binding characteristics of TXP antibodies from data obtained in immunoaffinity MS experiments, reducing the cost of such analyses. A multinomial statistical model explains the distributions of short sequences observed in protein databases. This allows deducing the average optimal length of the targeted epitope. Further a closed-from scoring function for epitope enrichment in sequence lists is derived

A Multi Agent System for Flow-Based Intrusion Detection Using Reputation and Evolutionary Computation

The rising sophistication of cyber threats as well as the improvement of physical computer network properties present increasing challenges to contemporary Intrusion Detection (ID) techniques. To respond to these challenges, a multi agent system (MAS) coupled with flow-based ID techniques may effectively complement traditional ID systems. This paper develops: 1) a scalable software architecture for a new, self-organized, multi agent, flow-based ID system; and 2) a network simulation environment suitable for evaluating implementations of this MAS architecture and for other research purposes. Self-organization is achieved via 1) a reputation system that influences agent mobility in the search for effective vantage points in the network; and 2) multi objective evolutionary algorithms that seek effective operational parameter values. This paper illustrates, through quantitative and qualitative evaluation, 1) the conditions for which the reputation system provides a significant benefit; and 2) essential functionality of a complex network simulation environment supporting a broad range of malicious activity scenarios. These results establish an optimistic outlook for further research in flow-based multi agent systems for ID in computer networks

Anonymous Post-Quantum Cryptocash

In this paper, we construct an anonymous and decentralized cryptocash protocol which is secure in the quantum computation model. In order to achieve that, a linkable ring signature based on the ideal lattice is proposed. The size of a signature in our scheme is O(log N ), where N is the number of participants in the ring. The framework of our cryptocash system follows that of CryptoNote with some modifications. By adopting the logarithmic size quantum resistant linkable ring signature scheme, our protocol is efficient and anonymous. We also introduce how to generate the verifying and signing key pairs of the linkable ring signature temporarily. With these techniques, both the sender and the receiver\u27s privacy in transactions are protected even though they are published in the public ledger