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The Future of Modular Architecture

• Published on June 09, 2021

Just published and available for purchase online, The Future of Modular Architecture presents an unprecedented proposal for mass-customized mid- and high-rise modular housing that can be manufactured and distributed on a global scale. The book’s thesis springs from the idea that adopting the dimensional standards of the existing intermodal freight transportation system is the key to achieving meaningful economies of scale.

Advocating for open-source design based on this new modular standard, the book shows how global supply chains can be harnessed to realize the long-held promise that housing will be a well-designed and affordable industrial product. We are on the cusp of a transformative change in the way we design and build our cities.

Author David Wallance FAIA argues that the future of modular architecture is profoundly intertwined with globalization, equitable urbanism, and sustainable development. His book addresses these timely issues through a specific approach grounded in fundamental concepts. Going beyond the individual modular building, Wallance forecasts the emergence of a new type of design, manufacturing, and construction enterprise.

From the book’s Foreword by Susan Szenasy: “Rising to the new and growing challenge [of societal issues] is architect David Wallance and his brilliant multi-disciplinary team. What follows is the inspiring story of creating a new approach to affordable urban housing from a product of worldwide commerce; and a deep understanding of global connections between the peoples of the Earth, in the 21st century.”

At 302 pages with 130 color illustrations, in hard-bound and paperback. the book represents 15 years of research, technical development, and design. Written in an approachable style, the book is a must read for professionals in architecture and design, urban planning, housing policy, construction, as well as the general reader with an interest in these topics.

PART 1 Chapter 1 Introduction Chapter 2 The Global Housing Crisis Chapter 3 The Argument for Economical Transportation Chapter 4 The Disruptive Advent of Intermodal Shipping Chapter 5 Promises of Progress: Four Case Histories

PART 2 Chapter 6 The Intermodal Modular System

PART 3 Chapter 7 Is Intermodal Modular Architecture Sustainable? Chapter 8 Innovators, Entrenched Interests, and Early Adopters Chapter 9 Toward a Global Vernacular Chapter 10 The Collaborative Open Source Project Chapter 11 The Place of Intermodal Modular Architecture

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Development and function explain the modular evolution of phalanges in gecko lizards

Selective regimes favouring the evolution of functional specialization probably affect covariation among phenotypic traits. Phalanges of most tetrapods develop from a conserved module that constrains their relative proportions. In geckos, however, biomechanical specializations associated with adhesive toepads involve morphological variation in the autopodium and might reorganize such modular structures. We tested two hypotheses to explain the modular architecture of hand bones in geckos, one based on developmental interactions and another incorporating functional associations related to locomotion, and compared the empirical support for each hypothetical module between padded and padless lineages. We found strong evidence for developmental modules in most species, which probably reflects embryological constraints during phalangeal formation. Although padded geckos exhibit a functional specialization involving the hyperextension of the distal phalanges that is absent in padless species, the padless species are the ones that show a distal functional module with high integration. Some ancestrally padless geckos apparently deviate from developmental predictions and present a relatively weak developmental module of phalanges and a strongly integrated distal module, which may reflect selective regimes involving incipient frictional adhesion in digit morphology. Modularity of digit elements seems dynamic along the evolutionary history of geckos, being associated with the presence/absence of adhesive toepads.

Evolution of two-component quorum sensing systems

Quorum sensing (QS) is a cell-to-cell communication system that enables bacteria to coordinate their gene expression depending on their population density, via the detection of small molecules called autoinducers. In this way bacteria can act collectively to initiate processes like bioluminescence, virulence and biofilm formation. Autoinducers are detected by receptors, some of which are part of two-component signal transduction systems (TCS), which comprise of a (usually membrane-bound) sensor histidine kinase (HK) and a cognate response regulator (RR). Different QS systems are used by different bacterial taxa, and their relative evolutionary relationships have not been extensively studied. To address this, we used the Kyoto Encyclopedia of Genes and Genomes (KEGG) database to identify all the QS HKs and RRs that are part of TCSs and examined their conservation across microbial taxa. We compared the combinations of the highly conserved domains in the different families of receptors and response regulators using the Simple Modular Architecture Research Tool (SMART) and KEGG databases, and we also carried out phylogenetic analyses for each family, and all families together. The distribution of the different QS systems across taxa, indicates flexibility in HK–RR pairing and highlights the need for further study of the most abundant systems. For both the QS receptors and the response regulators, our results indicate close evolutionary relationships between certain families, highlighting a common evolutionary history which can inform future applications, such as the design of novel inhibitors for pathogenic QS systems.

Motion Capture Sensor-Based Emotion Recognition Using a Bi-Modular Sequential Neural Network

Motion capture sensor-based gait emotion recognition is an emerging sub-domain of human emotion recognition. Its applications span a variety of fields including smart home design, border security, robotics, virtual reality, and gaming. In recent years, several deep learning-based approaches have been successful in solving the Gait Emotion Recognition (GER) problem. However, a vast majority of such methods rely on Deep Neural Networks (DNNs) with a significant number of model parameters, which lead to model overfitting as well as increased inference time. This paper contributes to the domain of knowledge by proposing a new lightweight bi-modular architecture with handcrafted features that is trained using a RMSprop optimizer and stratified data shuffling. The method is highly effective in correctly inferring human emotions from gait, achieving a micro-mean average precision of 0.97 on the Edinburgh Locomotive Mocap Dataset. It outperforms all recent deep-learning methods, while having the lowest inference time of 16.3 milliseconds per gait sample. This research study is beneficial to applications spanning various fields, such as emotionally aware assistive robotics, adaptive therapy and rehabilitation, and surveillance.

Towards a Modular Elbow Exoskeleton: Concepts for Design and System Control

AbstractIn industrial workplaces, strenuous, repetitive, and long-term tasks at head level or above as well as carrying heavy loads may lead to musculoskeletal disorders of different task dependent body parts. With an increasing trend towards wearable support systems, there is already a large quantity of exoskeletons that may support the user during movements, or stabilize postures, in order to reduce strain on various parts of the body. However, most commercially available exoskeletons mainly focus on the back and shoulder support. Only a few of them address the elbow joint, despite it being prone to injury. Therefore, this paper discusses different possible design and control concepts of modular elbow exoskeletons. The modular architecture potentially enables coupling to existing commercial- and research-associated systems, through appropriate interfaces. Different morphological structures and control mechanisms are assessed in respect to their ability to extend common exoskeletons for back and shoulder support. Based on these considerations, a first functional passive prototype is presented, which supports the flexion of the elbow joint and can be coupled to an existing exoskeleton. In future work, the prototype may be used for further elaboration and practical investigations in laboratory settings to evaluate its technical functionality and biomechanical effects on the user.

An Integrated Method for Modular Design Based on Auto-Generated Multi-Attribute DSM and Improved Genetic Algorithm

Modular architecture is very conducive to the development, maintenance, and upgrading of electromechanical products. In the initial stage of module division, the design structure matrix (DSM) is a crucial measure to concisely express the component relationship of electromechanical products through the visual symmetrical structure. However, product structure modeling, as a very important activity, was mostly carried out manually by engineers relying on experience in previous studies, which was inefficient and difficult to ensure the consistency of the model. To overcome these problems, an integrated method for modular design based on auto-generated multi-attribute DSM and improved genetic algorithm (GA) is presented. First, the product information extraction algorithm is designed based on the automatic programming structure provided by commercial CAD software, to obtain the assembly, degrees of freedom, and material information needed for modeling. Secondly, based on the evaluation criteria of product component correlation strength, the structural correlation DSM and material correlation DSM of components are established, respectively, and the comprehensive correlation DSM of products is obtained through weighting processing. Finally, the improved GA and the modularity evaluation index Q are used to complete the product module division and obtain the optimal modular granularity. Based on a model in published literature and a bicycle model, comparative studies are carried out to verify the effectiveness and practicality of the proposed method.

Mapping the Deformability of Natural and Designed Cellulosomes in solution

Abstract Background : Natural cellulosome multi-enzyme complexes, their components, and engineered ‘designer cellulosomes’ (DCs) promise an efficient means of breaking down cellulosic substrates into valuable biofuel products. Their broad uptake in biotechnology relies on boosting proximity-based synergy among the resident enzymes but the modular architecture challenges structure determination and rational design.Results: We used small angle X-ray scattering combined with molecular modeling to study the solution structure of cellulosomal components. These include three dockerin-bearing cellulases with distinct substrate specificities, original scaffoldins from the human gut bacterium Ruminococcus champanellensis (ScaA, ScaH and ScaK) and a trivalent cohesin-bearing designer scaffoldin (Scaf20L), followed by cellulosomal complexes comprising these components, and the nonavalent fully loaded Clostridium thermocellum CipA in complex with Cel8A from the same bacterium. The size analysis of Rg and Dmax values deduced from the scattering curves and corresponding molecular models highlight their variable aspects, depending on composition, size and spatial organization of the objects in solution.Conclusion: Our data quantifies variability of form and compactness of cellulosomal components in water and confirms that this native plasticity may well be related to speciation with respect to the substrate that is targeted. By showing that scaffoldins or components display enhanced compactness compared to the free objects, we provide new routes to rationally enhance their stability and performance in their environment of action.

A Modular Digital Twinning Framework for Safety Assurance of Collaborative Robotics

Digital twins offer a unique opportunity to design, test, deploy, monitor, and control real-world robotic processes. In this paper we present a novel, modular digital twinning framework developed for the investigation of safety within collaborative robotic manufacturing processes. The modular architecture supports scalable representations of user-defined cyber-physical environments, and tools for safety analysis and control. This versatile research tool facilitates the creation of mixed environments of Digital Models, Digital Shadows, and Digital Twins, whilst standardising communication and physical system representation across different hardware platforms. The framework is demonstrated as applied to an industrial case-study focused on the safety assurance of a collaborative robotic manufacturing process. We describe the creation of a digital twin scenario, consisting of individual digital twins of entities in the manufacturing case study, and the application of a synthesised safety controller from our wider work. We show how the framework is able to provide adequate evidence to virtually assess safety claims made against the safety controller using a supporting validation module and testing strategy. The implementation, evidence and safety investigation is presented and discussed, raising exciting possibilities for the use of digital twins in robotic safety assurance.

Linked Data: A Framework for Publishing FiveStar Open Government Data

With the increased adoption of open government initiatives around the world, a huge amount of governmental raw datasets was released. However, the data was published in heterogeneous formats and vocabularies and in many cases in bad quality due to inconsistency, messy, and maybe incorrectness as it has been collected by practicalities within the source organization, which makes it inefficient for reusing and integrating it for serving citizens and third-party apps. This research introduces the LDOG (Linked Data for Open Government) experimental framework, which aims to provide a modular architecture that can be integrated into the open government hierarchy, allowing huge amounts of data to be gathered in a fine-grained manner from source and directly publishing them as linked data based on Tim Berners lee’s five-star deployment scheme with a validation layer using SHACL, which results in high quality data. The general idea is to model the hierarchy of government and classify government organizations into two types, the modeling organizations at higher levels and data source organizations at lower levels. Modeling organization’s experts in linked data have the responsibility to design data templates, ontologies, SHACL shapes, and linkage specifications. whereas non-experts can be incorporated in data source organizations to utilize their knowledge in data to do mapping, reconciliation, and correcting data. This approach lowers the needed experts that represent a problem of linked data adoption. To test the functionality of our framework in action, we developed the LDOG platform which utilizes the different modules of the framework to power a set of user interfaces that can be used to publish government datasets. we used this platform to convert some of UAE's government datasets into linked data. Finally, on top of the converted data, we built a proof-of-concept app to show the power of five-star linked data for integrating datasets from disparate organizations and to promote the governments' adoption. Our work has defined a clear path to integrate the linked data into open governments and solid steps to publishing and enhancing it in a fine-grained and practical manner with a lower number of experts in linked data, It extends SHACL to define data shapes and convert CSV to RDF.

Support for Computing in Distributed Environments Based on Continuous Integration

Nowadays, tools for designing scientific applications often do not implement the required continuous integration capabilities of the applied software. Therefore, such overheads as the application development time and experiment execution makespan are substantially increased. In this regard, we propose a new approach to developing scientific applications and carrying out experiments with them. It is based on applying continuous integration to both the applied and system software in developing distributed applied software packages with a modular architecture using the Orlando Tools framework. Within the proposed approach, we provide integrating the Orlando Tools subsystems with the GitLab system and automating the development of package modules. At the same time, Orlando Tools fully support constructing and testing problem-solving schemes (workflows) that combine package modules located on environment resources with different computational characteristics. To this end, Orlando Tools provides the necessary configuring and setting up of computational resources. The practical significance of our study is substantial reduction overheads needed to experiment fulfillments and increase of the resource use efficiency.

Modularity Design Rules for Architecture Development: Theory, Implementation, and Evidence from the Development of the Renault–Nissan Alliance “Common Module Family” Architecture

In this paper, we propose a set of rules for developing modular architectures. We first consider the well-known concept of “Design Rules” advanced by Baldwin and Clark. We then propose a broader conceptualization called “Modularity Design Rules” that is derived from later studies of the strategic, managerial, and organizational processes that must also be undertaken to implement successful modular development projects. We elaborate the critical role that the proposed Modularity Design Rules play in strategically grounding, organizing, and managing modular architecture development processes. We also identify key roles that top management must fulfill in supporting implementation of the proposed rules. We then provide evidence in support of the proposed Modularity Design Rules through a case study of the Renault–Nissan Alliance’s successful development and use of a modular “Common Module Family” architecture between 2009 and 2014. We then suggest some important implications of the Modularity Design Rules for open innovation processes in new product development.

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Modular Architecture: When Beauty and Efficiency Meet

Modular architecture or “modularity in design” is a design approach that subdivides a system into smaller parts called modules or skids that can be independently created and then used in different systems. A modular system is characterized by functional partitioning into discrete scalable and reusable modules, rigorous use of well-defined modular interfaces, and making use of industry standards for interfaces.

The benefits of modular design are flexible in design and reduction in costs. Examples of modular systems are modular buildings, solar panels, wind turbines, and so on. The modular design combines the advantages of standardization with those of customization. A downside to modularity is that low-quality modular systems are not optimized for performance.

The Interlace, OMA, Ole Scheeren, © Iwan Baan

The Origin of Modular Design

Historically, in classical architecture, the diameter of a column was used as the basis for a number of modules. In Japanese architecture, room sizes were determined by combinations of rice mats which were 90x180cm. Matila Ghyka’s work on the golden section was one of the sources of the Modular, but his work, in general, was used by other architects, such as Le Corbusier ’s rival Andre Lurcat.

Lurcat proposed his own range of proportions related to the work of builders as much as to that of designers. Proportions and modules – thus became a central issue in the postwar French reconstruction, as architects struggled to maintain their status amid changing procedures in building production (Cohen, 2014).

What is the difference between modular and integral architecture?

A Modular village, fit for new Dyson students

There are many ways of categorizing architecture. Architecture can be either modular or integral. In reality, fully modular or fully integral architecture is rare and almost all architecture is somewhere in between.

On one hand, modular architecture has functionally de-coupled interfaces between components. In practice, this often leads to architecture that is one, where the functional elements in the building are mapped one-to-one to the components of the design.

However, integral architecture is the opposite of modular architecture. Integral architecture has coupled interfaces between components. It tends to have a more complex (not one-to-one) mapping from functional elements in the function structure to the components of the design (Holtta, 2005).

The Challenge of Modularity

Modularity means using the same module in multiple configurations enabling a large variety of designs without using any component types. This modularity brings several advantages such as reduced capital requirements and economies. Modularity is especially advantageous when the scale and scope of the project are relatively large. In such cases, it is a practical and economic option.

Through modularity, you can achieve various designs, while achieving low-cost development, as well as, cost-saving in design and construction. Thus, you find that modularity is pushing out the productivity frontier in design creation (McCluskey, 2000). On the contrary, modularity may lead to excess cost due to over-design, inefficient performance, and too many common modules may result in loss of design identity.

What is modular product architecture?

1. charles de gaulle international airport – terminal 2e (paris –france).

Charles-de-Gaulle airport, Terminal II, modules A & B, Paris, 1972-1982. Image © Labo ADP

The most recent, though surely not the final, extension of the Charles de Gaulle airport in Paris is Terminal 2E, completed in 2003. With a theoretical capacity of 11 million passengers per year and an area of 230,000 square meters, 2E is larger but less complex than the airline terminal 2F. 2E is an outgrowth of Andreu ’s work on 2F. The architect has insisted on developing and changing the design, rather than permitting a sterile reproduction of earlier designs (Jodidio, 2004).

Owing to its modular design, Terminal 2E was designed to address constant traffic conditions. The road infrastructure is part of the site’s entire composition as roads and viaducts come together and converge at the center of the terminal, flanked by two modules on each side. All these modules, located at the heart of the aircraft apron area, form four narrow 60 meter-wide buildings where travelers can see aircraft from the road. Each module is covered with trapezoidal shells forming four radiating arcs when seen from the sky.

Modular Design Approach

It is significant to use the modular approach in architectural designs. Modular design is characterized by properties such as upgradability, serviceability, flexibility, and so on. Also, the beauty of modular architecture is that you can replace or add any module without affecting the rest of the system. But, how important is it to encourage designers to use modularity? The answer is in the way we use modularity and the objectives of modular systems. Think of all the infinite numbers of architectural designs and forms we can create with a simple set of modules.

Written by: Riham Nady Edited by: Aiysha Alsane

  References

• Cohen, Jean-Louis. (2014). “ Le Corbusier’s Modulor and the Debate on Proportion in France ” . Architectural Histories, 2(1):23, pp.1-14.
• Holtta-Otto, Katja. (2005). “ Modular Product Platform Design ”. Doctoral Dissertation, Helsinki University of Technology. Finland.
• Jodidio, Philip. (2004). “ Paul Andreu Architect ”. BIRKHAUSER-Publishers for Architecture, Basal. Switzerland.
• McCluskey, Alan. (2000). “ Modularity: upgrading to the next generation design architecture ”. Business and Media official website: http://www.connected.org/media/modular.html.

Tags: Architecture Design Flexibility integral interfaces Le Corbusier Modular Modular architecture Paris Paul Andreu

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Understanding how platform modularity enhances network effects

• Research Paper
• Published: 05 August 2023
• Volume 33 , article number  40 , ( 2023 )

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• Qizhi Dai 1  

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With modular architecture, digital platforms comprise decomposable modules and well-defined interfaces that provide the technical capabilities for reconfiguring, extending, and evolving products. Drawing on research in engineering design and industrial economics, we investigate how the architectural modularity of platforms can be employed to enhance network effects. We illustrate how the structural elements and capabilities of modular architecture can be leveraged to strengthen network effects and how the objective of scaling platforms can drive the formulation of modularization principles to define modules and interfaces. We then discuss Microsoft Power BI, a business intelligence platform, as a specific example and describe how the components and functions of Power BI are utilized to strengthen network effects. Our study highlights the interplay between platform architecture and network effects, showing how architectural modularity can lead to network growth. It contributes to research on digital platforms and digital product innovation.

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Colloquium Paper

Smart, a simple modular architecture research tool: identification of signaling domains, jörg schultz.

* European Molecular Biology Laboratory, Meyerhofstr.1, 69012 Heidelberg, Germany; † Max-Delbrunk-Center for Molecular Medicine, Robert-Rössle-Str 10, 13122, Berlin, Germany; and § University of Oxford, The Old Observatory, South Parks Road, Oxford OX1 3RH, United Kingdom

Frank Milpetz

Chris p. ponting.

Accurate multiple alignments of 86 domains that occur in signaling proteins have been constructed and used to provide a Web-based tool (SMART: simple modular architecture research tool) that allows rapid identification and annotation of signaling domain sequences. The majority of signaling proteins are multidomain in character with a considerable variety of domain combinations known. Comparison with established databases showed that 25% of our domain set could not be deduced from SwissProt and 41% could not be annotated by Pfam. SMART is able to determine the modular architectures of single sequences or genomes; application to the entire yeast genome revealed that at least 6.7% of its genes contain one or more signaling domains, approximately 350 greater than previously annotated. The process of constructing SMART predicted ( i ) novel domain homologues in unexpected locations such as band 4.1-homologous domains in focal adhesion kinases; ( ii ) previously unknown domain families, including a citron-homology domain; ( iii ) putative functions of domain families after identification of additional family members, for example, a ubiquitin-binding role for ubiquitin-associated domains (UBA); ( iv ) cellular roles for proteins, such predicted DEATH domains in netrin receptors further implicating these molecules in axonal guidance; ( v ) signaling domains in known disease genes such as SPRY domains in both marenostrin/pyrin and Midline 1; ( vi ) domains in unexpected phylogenetic contexts such as diacylglycerol kinase homologues in yeast and bacteria; and ( vii ) likely protein misclassifications exemplified by a predicted pleckstrin homology domain in a Candida albicans protein, previously described as an integrin.

The functions of only a small fraction of known proteins have been determined by experiment. As a result, the use of computational sequence analysis tools is essential for the annotation of novel genes or genomes, and the prediction of protein structure and function. Currently, the most informative of these techniques are database search tools such as blast ( 1 ) and fasta ( 2 ) that identify similar sequences with associated statistical significance estimates. Current limitations of the use of these programs concern less the aspects of search sensitivity and more the functional annotation of identified homologues. Annotation terms such as “hypothetical protein” or “suppressor of spt3 mutations” are helpful neither to the user’s prediction of structure and function, nor to computational procedures attempting to automatically predict function from sequence.

An additional aspect concerns the annotation of complete genomes. Existing eubacterial and archaeal genomes have been analyzed with little regard to the existence of domains, because multidomain proteins in these organisms are relatively few in number. The domain as a functional and structural unit in eukaryotic proteins, however, is pre-eminent. For example, the majority of human extracellular proteins are multidomain in character (for reviews see refs. 3 and 4 ) and many complex eukaryotic signaling networks involve proteins containing multiple domains with catalytic, adaptor, effector, and/or stimulator functions ( 5 ). Several dozen of such “signaling domains” are known (for a review see ref. 6 ). The importance of modular proteins in disease is emphasized by the recent observation that the majority of positionally cloned human disease genes encode multidomain proteins, many of which are, in fact, signaling proteins ( 7 ). On the other hand, the view of the domain as a fundamental unit of structure and function is not universally accepted: not a single noncatalytic signaling domain is annotated in the widely distributed Saccharomyces cerevisiae genome directory that catalogs the genes of this complete genome ( 8 ).

Thus, there is a need to coordinate knowledge stored in the literature with that stored in sequence databases to facilitate the research of those in the scientific community who require the annotation of genes and genomes. It is our goal to provide an extensively annotated collection of cytoplasmic signaling domain alignments that enables rapid and sensitive detection of additional domain homologues as a Web-based tool.

Because it is difficult to distinguish those domains that perform cytoplasmic signaling roles from those that primarily function in transport, protein sorting, or cell cycle regulation, and for reasons of brevity, we shall discuss those domains that fall under two categories. ( i ) Cytoplasmic domains that possess kinase, phosphatase, ubiquitin ligase, or phospholipase enzymatic activities or those that stimulate GTPase-activation or guanine nucleotide exchange; these activities are known to mediate transduction of an extracellular signal toward the nucleus resulting in the initiation of a cellular response. ( ii ) Cytoplasmic domains that occur in at least two proteins with different domain organizations, of which one also contains a domain that is categorized under 1) (for a complete list of such domains see Table ​ Table1). 1 ).

Numbers of domains detected by SMART in the yeast genome, and in the yeast and human fractions of the Swiss Prot database

Numbers of domains detected by SMART in the yeast genome, and in the yeast and human fractions of the SwissProt database are compared with the numbers of domains derived from HMMer analysis and Pfam HMMs scanned against these database fractions, and the numbers of annotations in SwissProt. Many of these domains are reviewed elsewhere ( 5 , 6 ), and additional references may be found via the SMART Web site ( http://www.bork.embl-heidelberg.de/Modules/sinput.shtml ). 

Domain collections that cover a wide spectrum of cellular functions do exist in the forms of motif, alignment block, or profile databases such as prosite ( 9 ), blocks ( 10 ), prints ( 11 ), or Pfam ( 12 ) and provide a guide for the annotation of new proteins. However, there is a necessary trade-off in these collections between exhaustive coverage of domains and optimal sensitivity, specificity, and annotation quality. We have chosen to initiate the collection of gapped alignments of signaling domains because these are imperfectly covered in large collections and often include homologues with extremely divergent sequences. This collection is designed to be updated easily and is provided with a Worldwide Web interface enabling automatic sequence annotation with evolutionary, functional, and structural information. The resulting SMART procedure, a simple modular architecture research tool, offers a high level of sensitivity and specificity coupled with ease of use.

Construction of Multiple Sequence Alignments and Choice of the Search Program.

Of the 86 domain families, multiple alignments of 83 had been published previously (for references, see the annotation that accompanies the SMART Web site). These alignments were refined according to constraints described elsewhere ( 13 ) that included minimization of insertions/deletions in conserved alignment blocks, optimization of amino acid property conservation within these blocks, and closing of unnecessary gaps within insertion/deletion regions. Gapped alignments were constructed in preference to ungapped ones to allow the prediction of domain limits and as a result of their greater information content. Care was taken to build alignments that encompassed all secondary structures of domains whose tertiary structures are known. For remaining domains, investigations of sequence similarities beyond previously published domain limits were undertaken; this resulted in N-terminal extension of the previously described PX domain alignment by a single predicted β-strand, and identification of a conserved N-terminal motif in guanine nucleotide exchange factors for Ras-like GTPases. Prediction of domain limits also was aided by close proximities of domains to others with well-known limits, and to bona fide N- and C-terminal residues.

Alignments were updated to include additional predicted homologues. Because no single database searching algorithm currently is able to detect all putative homologues that are detectable by the combination of all searching methods ( 13 ), three iterative methods—HMMer, MoST, and WiseTools ( 14 – 16 )—were used to detect candidate homologues (HMMer and MoST thresholds: 25 bits and E < 0.01). Before their addition to multiple alignments, candidate homologue sequences were subjected to analyses using blast ( 1 ), Ssearch ( 2 ), and/or macaw ( 17 ) to estimate the statistical significance of sequence similarities ( psi-blast , blast , and Ssearch thresholds: E < 0.01). Those sequences that were considered homologues based on statistical significance estimates, and to a lesser extent on experimentally determined biological context, were used to construct alignments, profiles, and Hidden Markov models (HMMs).

As described above, care was taken to establish alignments representing entire structural domains. However, the termini were found to be the least conserved regions of alignments, and several profiles represent incomplete portions of domains. In two cases, phospholipase D and protein tyrosine phosphatase homologues, only short conserved “motifs” (conservation patterns representing an incomplete domain structure) are detectable across the domain family ( 18 – 20 ). For these examples, profiles/HMMs were calculated only from these short motifs to maximize the amino acid similarity signal-to-noise ratio ( 13 ).

Assignment and Calibration of Thresholds for Automatic Runs.

Score thresholds are required to provide automatic assignment of true positives and true negatives. There is no current method, including those that provide E- or p-value representations of score significances, that may be relied on to provide reliable values for these thresholds in all cases. As a result, manual intervention was necessary to estimate threshold values on the basis of published homology arguments and, for example, on the results of individual blast or Ssearch queries. SWise ( 16 ) was chosen as an established algorithm able to provide similarity scores for query sequences when compared with the alignment database; however, the SMART database method can be applied to any algorithm that provides similarity scores.

For each alignment an SWise ( 16 ) threshold ( T p ) was established that represents the lowest score allowable for sequences to be considered as “true positives” or homologues. As such, this single step procedure detects many true positives but does not detect few previously proposed homologues (“false negatives”) that score at levels just below that of the top “true negative.” A proportion of false negatives could not be assigned as homologues without further statistical evidence. However, consideration that domains such as ARM, C2, CBS, IQ, LIM, PDZ, SH2, SH3, and WW (Table ​ (Table1) 1 ) frequently are found as repeats, enabled several false negatives to be detected by using estimations of an additional threshold value, T r ( T r < T p ). T r represents a repeats’ threshold for a protein where at least one of the repeats scores above T p (Fig. ​ (Fig.1). 1 ). Two or more repeats scoring above the average of T p and T r [( T p + T r )/2] also were considered false negatives. Some domains that appear to be found only as tandem repeats (for example, EF-hands, tetratricopeptide repeats, and armadillo repeats) are reported only if two or more copies are found that score above a low threshold T r . To predict the subfamily of a particular domain (for example, whether a tyrosine or a serine/threonine kinase, or whether a tyrosine-specificity or a dual-specificity phosphatase) further thresholds T s ( T s > T p ) also were estimated; no subfamily predictions are made for those domain homologues that score above T p but below T s .

Calibration of thresholds. Selection of thresholds from the distributions of SH3 domain scores. ( Upper ) A histogram of SWise scores for the best match (optimal alignment; in green) of proteins with a SH3 domain profile. ( Lower ) Similar histograms for the second- and third-best matches (suboptimal alignments; in light blue and dark blue, respectively). Optimal alignment scores less than threshold T p are mostly derived from sequences considered unlikely to contain SH3 domain homologues. Threshold T p was selected as the lowest scoring true positive. Domains that are repeated twice or more in the same protein that each score above a lower threshold ( T r ) are considered to be true negatives.

Subset alignments of a given domain family were constructed not only to improve the specificity of functional predictions, but also for divergent families for which a single descriptor (profile/HMM) was found to be unable to detect the entire set of known homologues (e.g., C2 and pleckstrin homology (PH) domains; refs. 21 and 22 ). Construction of multiple profiles each representing different regions of the domain phylogenetic tree resulted in “overlapping” profiles that, when used in combination, found the maximal number of homologues. Sensitivity and specificity is guaranteed with combinations of T s and T p . Overlapping hits from nonhomologous profiles, which can occur because of inserted domains ( 23 ), all are reported.

Seeding and Updating Procedure.

To reduce redundancy and subfamily bias within sequence families, seed alignments were calculated by using an iterative semiautomatic procedure. In a first step all database sequences considered homologous, given the threshold procedures described above, are subjected to a clustalw phylogenetic tree construction ( 24 ). Only a single sequence from every branch of the tree that is shorter than a defined threshold (the default distance is 0.2, which corresponds approximately to 80% identity, ref. 24 ) is retained in the alignment. From this seed alignment, a profile is derived leading to reiteration of the database search procedure until convergence. For example, four iterations were required to build a Src homology 2 (SH2) seed alignment containing 95 sequences, of a total of 548 SH2 domains identified in the translated EMBL sequence database.

With new sequences entering databases daily, seed alignments and derived profiles need to be updated accordingly. SMART incorporates a facility whereby database daily updates are screened for the presence of signaling domains. Those that represent a new branch of the domain family phylogenetic tree (i.e., with a distance of greater than 0.2) are recorded for inclusion in future SMART domain set updates. The alignments are accessible via the SMART Web server.

Implementation into a Web Server.

SMART has been provided with a user interface ( http://www.bork.embl-heidelberg.de/Modules/sinput.shtml ) that allows rapid and automatic annotation of the signaling domain composition of any query protein sequence. A graphical display is provided showing domain positions within the query sequence. The SMART set of signaling domains is annotated extensively via hyperlinks to Medline and the Molecular Modeling Database via Entrez ( 25 ), thus providing easy access to information relating sequence, homology, structure, and function. As the set of signaling sequences is necessarily incomplete and as there may be other domains represented in the query sequence, direct access also is provided to Pfam ( 12 ), a domain database that includes a variety of different domain types, yet provides a lower representation of signaling domains and with lower sensitivity (see Discussion ). Intrinsic features of the query such as coiled coil regions ( 26 ), low complexity regions ( 27 ), and transmembrane regions ( 28 ) also are displayed. Annotated or unannotated regions of the query sequence are able to be subjected individually to gapped blast searches ( 1 ), thus allowing the advantage of a reduced search space enabling higher sensitivity in searches.

Benchmarking Protocol.

To assess the sensitivity and selectivity of SMART, results were compared with annotations held by SwissProt, because this represents the best-annotated protein sequence database extant, (and includes all those annotations covered by the prosite database) as well as with the Pfam domain collection, because this represents the most comprehensive set of gapped alignments available ( 12 ). Our intention here was not to provide justifications for the inclusion or exclusion of particular sequences in domain alignments, but to compare literature information as represented by the SMART database, with the same information as represented by SwissProt and Pfam databases. All S. cerevisiae and human sequences were extracted from SwissProt and annotated by using the SMART protocol. Because these organisms are well-studied and their proteins relatively well-annotated they represent a stringent test for annotation procedures. The SMART domain annotations were compared manually with those derived from HMMer ( 14 ) analysis, and those contained in SwissProt (Table ​ (Table1); 1 ); the hmmfs program and a 25-bits threshold was used for the HMMer analysis. As the SwissProt release 34 does not contain all yeast sequences, the complete set of S. cerevisiae ORFs also was subjected to SMART analysis (Table ​ (Table1 1 ).

Comparison with SwissProt and Pfam.

Of all protein sequence databases, SwissProt is the most extensively annotated, making use of literature- and sequence-derived ( 9 ) data as source material. As a result the SwissProt database is a valuable resource for investigators searching for hints of the structure and function of their sequences of interest. Consequently, it is appropriate to compare SMART-derived annotations with those contained in SwissProt.

SMART detected 548 and 1,137 domains in the yeast and human subsets of SwissProt, respectively (Table ​ (Table1). 1 ). Of these, 165 and 251 domains (30% and 22%, respectively) are not annotated in SwissProt. Many of these belong to the 29 domain families that are contained in SMART and yet are not annotated in SwissProt. By contrast, all SwissProt annotations relating to our domain set were detected by SMART, with the exception of a small set of domain fragments. Only 23 of the SMART domain families are represented by Prosite motifs or patterns. Moreover, because Prosite motifs commonly represent active site regions, it is apparent that these do not detect the several homologues of kinases, phosphatases, or ubiquitin-conjugating enzymes that have dispensed with their active site residues.

The current set of Pfam HMMs, when compared with the yeast and human SwissProt subsets, detected 290 and 704 domains. Forty-six of the 86 SMART domain types are not represented currently in Pfam. Moreover, the Pfam set does not yet allow subfamily annotation for domain families such as small GTPases, protein kinases, or protein phosphatases. Pfam and HMMer were able to identify several incomplete domain sequences that SMART could not. SMART was not designed to detect domain fragments because it was considered valuable to detect complete domains, thereby allowing assignment of putative domain boundaries. Consequently, the HMMer (hmmfs) option of SMART has been provided to allow detection of incomplete domain sequences.

Identification of Signaling Domains in Yeast.

Annotation of the complete yeast genome (6218 ORFs) revealed that 420 yeast proteins (6.7%) contain at least one of the domains included in SMART. This is larger than a previous estimate that 2% of yeast proteins are involved in signaling ( 8 ), which approximates to the percentage of S. cerevisiae proteins known to be kinase homologues. SMART identifies a total of 622 domains (Table ​ (Table1); 1 ); two or more domains occur in 96 of the 420 signaling proteins. Results of the SMART annotation of yeast proteins identified are summarized in a Web page ( http://www.bork.embl-heidelberg.de/Modules/syeast.html ), which was generated by using SMART’s graphical output features.

These results imply an improvement by SMART on other tools and current best-annotated databases in the particular field of signaling. An additional feature of SMART is its ability to facilitate predictions of the structures and/or functions of proteins when a hit is recorded. The following examples illustrate several such instances that arise from a domain hit.

Domain Annotation and Deduction of Functional Features.

During construction of the SMART database, tensin and focal adhesion kinase (pp125 FAK ), which both are localized to focal contacts, were found to contain previously unrecognized domains. Fig. ​ Fig.2 2 a shows the modular architecture of tensin, an actin filament capping protein that is known to contain large coiled coil regions, an SH2 ( 29 ) and an N-terminal domain homologous to protein tyrosine phosphatases (PTPs) ( 20 ). SMART predicts a phosphotyrosine binding domain (PTB; also called phosphotyrosine interaction [PI] domain) (Table ​ (Table1) 1 ) in tensin’s most C-terminal region, which has not previously been ascribed a domain homology. Each of tensin’s three globular domains—PTP, SH2, and PTB/PI—have been implicated in phosphotyrosine-mediated signaling. This is consistent with previous findings that tensin is a substrate of the tyrosine kinase pp125 FAK ( 30 ), which is also highly tyrosine-phosphorylated when activated (reviewed in ref. 31 ).

Schematic representations, produced using SMART, of the domain architectures of proteins discussed in the text. See Table ​ Table1 1 for the identified domains; gray lines (no SMART match) might contain other known domains not included in SMART. Putative homologues were identified during SWise ( 16 ) searches and/or psi-blast ( 1 ) searches ( E < 0.01). ( a ) Domain recognition: A novel PTB domain was identified in tensin, resulting in completion of its modular architecture assignment. A psi-blast search with a previously predicted PTB domain in C. elegans F56D2.1 ( 53 ) yields the tensin PTB after four passes. Prediction of molecular function via domain hit: Identification of a domain homologous to band 4.1 protein in focal adhesion kinase (FAK) isoforms. FAKs are predicted to bind cytoplasmic portions of integrins in a similar manner to that of talin, another band 4.1 domain-containing protein. A psi-blast search with a band 4.1-like domain (41 HUMAN, residues 206–401) revealed band 4.1-like domains in human, bovine, and Xenopus FAK isoforms by pass 3. ( b ) Detection of new domains because of search space reduction: Putative DEP domains in ROM1 and ROM2 were identified by using SWise ( 16 ) and HMMer ( 14 ), but could not be detected by using psi-blast . Analysis of the regions surrounding identified domains revealed the presence of a novel domain in the C-terminal regions of ROM1 and ROM2 that occurs also in several Ste20-like protein kinases, and mouse citron (CNH, citron homology). A gapped blast search of the region of citron C-terminal to its PH domain (CTRO MOUSE, residues 1134–1457) reveals significant similarity with yeast ROM2 ( E = 1 × 10 −5 ). ( c ) Functional predictions for an entire domain family: A region of p62 known to bind ubiquitin ( 40 ), and its homologous sequence in the Drosophila protein ref(2)P, scored as the highest putative true negatives in a SWise search. We predict ubiquitin-binding functions for UBA domains. psi-blast searches were unable to corroborate this prediction. ( d ) Prediction of cellular functions: Although not indicated in the primary sources ( 43 , 44 ), a DEATH domain was found in rcm and other UNC5 homologues, in agreement with a previous claim ( 41 ). At the molecular level, this domain in UNC5 is predicted to form a heterotypic dimer with an homologous domain in UNC44 implying a cellular role in axon guidance. A gapped blast search with the known DEATH domain of death-associated protein kinase (DAPK HUMAN, residues 1304–1396) predicts a DEATH domain in rat UNC5H1 with E = 9 × 10 −3 ). ( e ) Signaling domains in “disease genes”: Pyrin or marenostrin, a protein that is mutated in patients with Mediterranean fever and is similar to butyrophilin, contains a SPRY domain. psi-blast with the SPRY domain of human DDX1 (EMBL: {"type":"entrez-nucleotide","attrs":{"text":"X70649","term_id":"3123573","term_text":"X70649"}} X70649 , residues 124–240) yields a butyrophilin homologue by pass 5 and pyrin/marenostrin (residues 663–759) by pass 7. ( f ) Homologues of domains involved in eukaryotic signaling may not be eukaryotic-specific: DAG kinases have been found previously in mammals, invertebrates, plants, and slime mold. However, it is apparent that DAG kinase homologues of unknown function are present in yeasts and in eubacteria (see Fig. ​ Fig.3). 3 ). A gapped blast search with Bacillus subtilis bmrU (BMRU BACSU) yields significant similarities with Arabidopsis thaliana DAG kinase (KDG1 ARATH; E = 4 × 10 −4 ) and a Schizosaccharomyces pombe ORF (SPAC4A8.07c; E = 1 × 10 −7 ). ( g ) Identification of potential misclassifications: A PH domain and the lack of an obvious transmembrane sequence indicates a cytoplasmic and signaling role for a protein (INT1 CANAL) previously thought to be a yeast integrin. A psi-blast search with the N-terminal PH domain of pleckstrin yielded INT1 CANAL in pass 3.

Application of SMART procedures to pp125 FAK homologues predicts band 4.1-homologous domains in their N-terminal regions that bind the cytoplasmic regions of integrins ( 32 ) (Fig. ​ (Fig.2 2 a ). Although one has to be cautious when inferring functional information simply from domain identification, on this occasion the band 4.1 domains are likely to perform similar molecular functions because talin, another band 4.1 domain-containing protein, is known also to bind integrin cytoplasmic domains ( 33 ).

Reducing the Search Space Enables Identification of Novel Domains.

S. cerevisiae ROM1 and ROM2 are sequence-similar proteins that each contain a PH domain and a RhoGEF domain that stimulates exchange of Rho1 GDP with Rho1 GTP ( 34 ). Construction of the SMART databases led to the identification of a putative DEP domain ( 35 ) in both ROM1 and ROM2 (Fig. ​ (Fig.2 2 b ). Comparison of the ROM1 and ROM2 sequences showed a further region of similarity C-terminal to their PH domains. This region [“citron-homology” (CNH) domain] was identified as being homologous to the mouse Rho GTP /Rac GTP -binding protein, citron ( 36 ) and to the C-terminal regions of several Ste20-like protein kinases (Fig. ​ (Fig.2 2 b ). A novel domain family (VHS) of unknown function(s) also has been detected in Vps27, Hrs, and STAM, and other proteins.

A conserved domain in Cdc25p-like proteins mediates their activities as guanine nucleotide exchange factors for Ras or Ral ( 37 ). Each of these molecules contain N-terminal extensions. We find additional amino acid similarities in these regions, and these represent a novel domain family (Fig. ​ (Fig.3). 3 ). Surprisingly, this domain (which we call RasGEFN) can be contiguous to, or far from, the catalytic domain. A construct of p140 Ras-GRF that lacks this region is constitutively active ( 38 ), so it is likely that the RasGEFN domain performs a suppressor function.

Multiple alignments of selected RasGEFN domains. A conserved region was found in the N-terminal regions of several proteins with RasGEF (Cdc25-like) domains ( 37 ). Surprisingly, this N-terminal domain may be present in the sequence either close to, of far from, the RasGEF domain. A psi-blast search using a region (residues 898–946) of C. albicans Cdc25 (CC25 CANAL) and E < 0.01, identified each of the sequences in Fig. ​ Fig.3 3 within nine passes before convergence. Predicted ( 54 ) secondary structure and 90% consensus sequences are shown beneath the alignments; SwissProt/PIR/EMBL accession codes and residue limits are given after the alignments. Residues are colored according to the consensus sequence [green: hydrophobic (h), ACFGHIKLMRTVWY; blue: polar (p), CDEHKNQRST; red: small (s), ACDGNPSTV; red: tiny (u), AGS; cyan: turn-like (t), ACDEGHKNQRST; green: aliphatic (l), ILV; and, magenta: alcohol (o), ST). The SwissProt sequence KMHC DICDI has been altered to account for probable frameshifts.

Deducing Functional Features of a Domain Family Via a Protein Hit.

Although rare, we have identified additional members of a domain family in regions of proteins that already have been shown to perform particular functions. Such findings often suggest comparable functions for all other members of the domain family. The ubiquitin-associated (UBA) domain (Table ​ (Table1) 1 ) has been shown to be contained in several enzymes implicated in ubiquitination ( 39 ). We have identified a UBA domain in a region of p62, a phosphotyrosine-independent ligand of the p56 lck SH2 domain ( 40 ) that is known to bind ubiquitin (Fig. ​ (Fig.2 2 c ). Ubiquitin-binding functions are predicted for other UBA domains.

Prediction of Cellular Function.

Particular domains have been implicated in certain cellular events. For example, DEATH domains (Table ​ (Table1) 1 ) are present in proteins associated with apoptosis and/or axonal guidance ( 41 , 42 ). Recent reports ( 43 , 44 ) identify the rostral cerebellar malformation gene product (rcm) and similar homologues as putative netrin receptors. These reports do not indicate the presence of a DEATH domain in rcm or its homologues, even though the domain’s presence may be readily demonstrated by sequence analysis (Fig. ​ (Fig.2 2 d ) or from its identification in the rcm Caenorhabditis elegans orthologue, UNC-5 ( 41 ). As the DEATH domain of UNC-5 is not annotated in databases, this is one of many instances where the potential of domain identification to predict cellular function has been unfulfilled. DEATH domains often form homotypic or heterotypic dimers ( 42 ). Because DEATH domain-containing proteins UNC-44 ( 45 ) and the putative netrin-receptor UNC-5 are known to be involved in axonal guidance, we predict that transduction of the netrin-initiated signal involves heterodimerization of UNC-5 and UNC-44 DEATH domains.

Identification of Signaling Domains in Genes That Are Involved in Diseases.

A recent study of 70 positionally cloned human genes mutated in diseases found that a significantly high proportion of these “disease genes” possess roles in cell signaling ( 7 ). In accordance with this, the SMART alignment database contains several novel signaling domains in these genes (including the DEATH domain in rcm-like netrin receptors, see above). Fig. ​ Fig.2 2 e shows the modular architecture of pyrin ( 46 ) (also called marenostrin; ref. 47 ). Mutations in the pyrin gene result in Mediterranean fever syndromes that are inherited inflammatory disorders. In addition to its ret-like zinc finger, pyrin/marenostrin and other butyrophilin-like homologues contain a SPRY domain, a domain of unknown function found triplicated in ryanodine receptors and singly in other proteins ( 48 ) (Table ​ (Table1). 1 ). Midline 1, a pyrin-homologue that also contains a SPRY domain, is mutated in patients with Opitz G/BBB syndrome ( 49 ).

Identification of Domains in Different Phyla.

The range of species in which a particular domain type is found can correlate with the evolution of specific signaling pathways; many of the known cascades are expected only in animals or eukaryotes ( 3 ). Thus, identification of DAG kinase homologues in yeast and eubacteria (Fig. ​ (Fig.2 2 f ) is clearly a surprise. Although further experimentation is required to infer functional features, the presence of conserved, presumably catalytic, residues in the alignment (data not shown) and the occurrence of DAG kinase activities in prokaryotes ( 50 ) suggests that the yeast and bacterial DAG kinase homologues possess similar molecular, but perhaps not cellular, roles to those of their animal and plant homologues.

Significance of Domain Detection and Functional Prediction.

Annotation of molecular function in sequence databases and even in the literature is difficult to interpret given that the term function may describe phenomena occurring at distinct levels, such as those of amino acids, domains, proteins, molecular complexes, cells, or organisms. Nevertheless, the examples shown above demonstrate that annotation of a certain domain can provide useful hints toward experimental characterization of function at different levels. Domain identification also might provide a counter-argument to a previously proposed molecular function. For example, identification of a PH domain and the absence of a detectable transmembrane region in a supposed integrin from C. albicans (Fig. ​ (Fig.2 2 g ) argues strongly against its proposed role in cell adhesion ( 51 ). Integrins are transmembrane proteins that link the extracellular matrix with the cytoskeleton and normally contain, except for the B-4 subunit, short cytoplasmic sequences. The finding of a PH domain and high sequence similarity to S. cerevisiae BUD4 argues for its signaling role in bud site selection.

Many proteins are multidomain in character and possess multiple functions that often are performed by one or more component domains. A Web-based tool (SMART) has been designed that makes use of mainly public domain information to allow easy and rapid annotation of signaling multidomain proteins. The tool contains several unique aspects, including automatic seed alignment generation, automatic detection of repeated motifs or domains, and a protocol for combining domain predictions from homologous subfamilies. The ability of SMART to annotate single sequences or large datasets is exemplified by the cases described in Results , including annotation of the complete set of yeast ORFs.

Currently, large-scale or genome analysis is commonly performed by annotating ORFs with a single “best hit” from similarity searches. Ambiguities whether hits represent orthologs (i.e., homologues in different organisms that arose from speciation rather than intragenome duplication and are likely to have a corresponding function; ref. 52 ) or else paralogs (other members of multigene families) are not solved and omission of domain annotation also leads to misprediction of function. As most signaling proteins are multidomain in character, only annotation at the domain level avoids ambiguities in assigning homologies and functions to sequences, which may propagate further on additional findings of homology. Furthermore, deduction of the modular architecture is essential for the understanding of the complexities of multidomain eukaryotic signaling molecules; current annotation, however, does not adequately provide this information (Table ​ (Table1). 1 ). As examples of this, the existence of noncatalytic signaling domains cannot be deduced from the current yeast genome directory ( 8 ) and no human RasGEF domains currently are annotated in SwissProt. Graphical representation of the complement of modular proteins in a completed genome (e.g., the 622 signaling domains in 420 yeast proteins: http://www.bork.embl-heidelberg.de/Modules/syeast.html ) might provide the basis for relating experimentally derived information concerning domains and multidomain proteins, to cellular events such as signaling.

Although other collections, such as prosite , Pfam, blocks , and prints , contain many more distinct domains or motifs, the focus of SMART on signaling allows significantly enhanced detection sensitivity, the inclusion of many families that are not represented in other collections, and offers a high level of specificity (i.e., a low rate of false positives that is essential for large-scale analysis). The SMART database shall be continually updated; alignment updates shall be semiautomated to avoid misalignments. Thus, forthcoming SMART database versions shall be hand-checked to provide datasets of high quality. In future, experimental findings that advance the understanding of domain structure and function also shall be provided via updates. As SMART is designed to obtain biologically relevant results without dependency on a single database search technique, there is potential to modify underlying methods to improve performance.

Acknowledgments

We thank colleagues at the European Molecular Biology Laboratory and Ewan Birney for many helpful discussions. We also thank Bernhard Sulzer for computational assistance. C.P.P. is a Wellcome Trust Career Development Fellow and a member of the Oxford Centre for Molecular Sciences, and was supported in part by a European Molecular Biology Organization Short-Term Fellowship. J.S. and P.B were supported by the European Union, Bundesministerium für Bildung und Forschung (Germany), and the Deutsche Forschungsgemeinschaft.

ABBREVIATIONS

Note added in proof.

Recent improvements to the SMART system include implementation of SWise-derived E-values and addition of more than 80 extracellular domains. A ProfileScan Server ( http://ulrec3.unil.ch/software/PFSCAN_form.html ) has appeared recently that includes facilities that are similar or complementary to those of SMART.

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Physics > Applied Physics

Title: low-loss liquid metal interconnects for modular superconducting quantum systems.

Abstract: Building modular architecture with superconducting quantum computing chips is one of the means to achieve qubit scalability, allowing the screening, selection, replacement, and integration of individual qubit modules into large quantum systems. However, the non-destructive replacement of modules within a compact architecture remains a challenge. Liquid metals (LM), specifically gallium alloys, can be alternatives to solid-state galvanic interconnects. This is motivated by their self-healing, self-aligning, and other desirable fluidic properties, potentially enabling non-destructive replacement of modules at room temperatures, even after operating the entire system at millikelvin regimes. In this study, we present high-internal-quality-factor coplanar waveguide resonators (CPWR) interconnected by gallium alloy droplets, demonstrating performance on par with the continuous solid-state CPWRs. Leveraging the desirable fluidic properties of gallium alloys at room temperature and their compact design, we envision a modular quantum system enabled by liquid metals.

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