bluuebunny/crossref_metadata_2025 huggingface dataset:
Religion in Post-1945 America
Authors: Dochuk Darren
Published: September 2016

Jimmy Carter’s “Crisis of Confidence Speech” of July 1979 was a critical juncture in post-1945 U.S. politics, but it also marks an exemplary pivot in post-1945 religion. Five dimensions of faith shaped the president’s sermon. The first concerned the shattered consensus of American religion. When Carter encouraged Americans to recapture a spirit of unity, he spoke in a heartfelt but spent language more suitable to Dwight Eisenhower’s presidency than his own. By 1979, the Protestant-Catholic-Jewish consensus of Eisenhower’s time was fractured into a dynamic pluralism, remaking American religion in profound ways. Carter’s speech revealed a second revolution of post-1945 religion when it decried its polarization and politicization. Carter sought to heal ruptures that were dividing the nation between what observers, two decades hence, would label “red” (conservative Republican) and “blue” (liberal Democratic) constituencies. Yet his endeavors failed, as would be evidenced in the religious politics of Ronald Reagan’s era, which followed. Carter championed community values as the answer to his society’s problems aware of yet a third dawning reality: globalization. The virtues of localism that Carter espoused were in fact implicated in (and complicated by) transnational forces of change that saw immigration, missionary enterprises, and state and non-state actors internationalizing the American religious experience. A fourth illuminating dimension of Carter’s speech was its critique of America’s gospel of wealth. Although this “born-again” southerner was a product of the evangelical South’s revitalized free-market capitalism, he lamented how laissez-faire Christianity had become America’s lingua franca. Finally, Carter wrestled with secularization, revealing a fifth feature of post-1945 America. Even though faith commitments were increasingly cordoned off from formal state functions during this time, the nation’s political discourse acquired a pronounced religiosity. Carter contributed by framing mundane issues (such as energy) in moral contexts that drew no hard-and-fast boundaries between matters of the soul and governance. Drawn from the political and economic crises of his moment, Carter’s speech thus also reveals the all-enveloping tide of religion in America’s post-1945 age.
Spirituality and Contemporary Art
Authors: Arya Rina
Published: September 2016

The artworks under discussion detail the scope and breadth of art that can be described as spiritual by virtue of its revelatory, revitalizing and contemplative capacities. Rather than interrogating the relationship between art and religion, more pertinent questions in the contemporary age are: What is the nature of the dialogue between art and spirituality, how do the two come together, and what form does the meeting take? The range of multimedia brings novel forms of encounter that occur outside the gallery and other spaces and involve audio-visual and other means of articulating the spiritual. These new forms make different demands on viewers; they create greater intimacy (often through immersion), both physically and psychologically, and one of the consequences of having greater intimacy can be a heightened awareness that increases presentness and a sense of embodiment. What we learn is that there are potentially as many interpretations of spirituality as there are viewers.
Martin Luther, Dietrich Bonhoeffer, and Political Theologies
Authors: DeJonge Michael P.
Published: September 2016

Contemporary political theology often defines itself against Lutheran social ethics, which is portrayed as politically disengaged and overly deferential to state power. At the same time, contemporary political theology often embraces the Lutheran theologian Dietrich Bonhoeffer as an exemplary political theologian. This incongruity is generally resolved by distancing Bonhoeffer from his tradition, at least on matters of political theology. But Bonhoeffer’s political theology was thoroughly Lutheran. Throughout the years of his political-theological engagement, from the Nazi rise to power in 1932–1933 to the drafting of Ethics and related writing in 1940–1943, he participated in ongoing conversations within Lutheran social ethics on the issues of, among others, the two kingdoms and the orders. In the process, he critically appropriated these elements of Lutheran thinking into an especially dynamic and christocentric framework that in turn informed his positions on various issues such as the church’s proclamation against the Nazi state and the ecumenical church’s witness for peace. Bonhoeffer is an example of Lutheran political theology, one that suggests the need to revise at least the more sweeping judgments about Lutheran theology as inherently incompatible with political engagement.
Martin Luther’s Perspectival Eschatology
Authors: Westhelle Vítor
Published: September 2016

Eschatology was until recently a mute locus in the treatment of Luther’s dogmatic, subsumed under the doctrine of justification. There is now a significant agreement as to the eschatological and soteriological significance of the presence of Christ in faith made effective through his cross and resurrection. This pertains to the coram Deo perspective. In the coram mundo perspective, however, eschatology assumes spatial and temporal dimensions and finds expression in mundane boundaries and limits (ta eschata). Luther’s approach to eschatology, then, has two foci, one addressing presence and the other focusing on representations. If in justification all is simultaneous, in works there are distinctions. In one the theological operational category is faith, while in the other it is love.

While the two foci of eschatology are expressed by the two perspectives of the relationship humans have to God and to the world, eschatology in the latter entails two aspects of their implications. One deals with the private individual: death, bodily resurrection, eternal life, final judgment, and the soul’s immortality. The immortality of the soul has been a disputed issue in Luther research but in the end largely irrelevant, considering that the resurrection pertains to the whole human being; the soul and the glorified body will enter eternal bliss with the final judgment. As to this judgment, the restoration of all things (apokatastasis pantōn) is clearly rejected, and yet the eternal damnation of the wicked is not a forgone conclusion. The final revelation, when God will be all in all, will be unveiled only in the light of glory (lumen gloriae) whose mystery Luther claims not to know: nescio.

The other aspect of the earthly dimension has a social and cosmic component in which it is represented by the limits demarcated by the public spheres or orders instituted by God. These are realms in which reason is publicly exercised in work done for the sake of the requirements of the law. The public spheres are instruments in the earthly realm against the work of the devil (ecclesia, oeconomia, and politia), which are the three public realms under the single canopy of Christian love. And this love demands reason and efficacy for the sake of justice and equity. It pertains to sanctification, not to salvation. In the worldly perspective, Luther was susceptible to the end-time speculations of his days, producing even (as a diversion, he claimed) a world historical calendar predicting the arrival of the cosmic Sabbath.

The nodal point connecting these two eschatological foci rests in Luther’s interpretation of the Chalcedonian communicatio. The earthly dimension of eschatology is one with the spiritual, as the person of the incarnate logos cannot be divided. That God creates what God loves is true from creation to consummation; protology and eschatology are one in Christology, while the distinction remains without confusion as long as creation subsists and the love of God abides.
Martin Luther and Justification
Authors: Vainio Olli-Pekka
Published: September 2016

The doctrine of justification is an account of how God removes the guilt of the sinner and receives him or her back to communion with God. The essential question concerns how the tension between human sin and divine righteousness is resolved. Luther’s central claim is that faith alone justifies (that is, makes a person righteous in the eyes of God) the one who believes in Christ as a result of hearing the gospel. This faith affects the imputation of Christ’s righteousness that covers the sins of the believer. In contrast to medieval doctrines of justification, Luther argues that Christ himself, not love, is the form, or the essence, of faith. Love and good works are the necessary consequences of justification even if they are not necessary for justification. However, the inclination to love and perform good works is present in the believer through Christ, who is present in faith, but these characteristics do not as such, as renewed human qualities, have justifying power.

Luther’s doctrine of justification cannot be classified with simplistic categories like “forensic” and “effective” (see the section “Review of the literature” below). Often these terms are used to refer to differing interpretations of justification. However, several recent traditions of scholarship perceive this categorical differentiation as simplistic and misleading. Instead, these terms may well function to designate different aspects of God’s salvific action. In the narrow sense, justification may refer to the forensic and judicial action of declaring the sinner free from his or her guilt. A broader sense would include themes and issues from other theological doctrines offering a holistic and effective account of the event of justification, in which the sinner believes in Christ, is united with Christ’s righteousness, and receives the Holy Spirit.

Depending on the context, Luther may use both narrow and broad definitions of justification. Here Luther’s doctrine of justification is approached from a broader perspective. On the one hand, justification means imputation of Christ’s alien righteousness to the believer without merits. On the other hand, faith involves effective change in the believer that enables one to believe in the first place. This change is not meritorious because it is effected by Christ indwelling in the believer through faith. Thus, Christ gives two things to the sinner: gratia, that is, the forgiveness of sins, and donum, that is, Christ himself. The media through which Christ offers his mercy are the word and sacraments. Thus, Luther’s sacramental theology, Christology, and soteriology form a coherent whole. Because justification involves union with Christ, which means participation in Christ’s divine nature, Luther’s doctrine of justification has common elements with the idea of deification.
Martin Luther on the Vocations of the Christian
Authors: Benne Robert
Published: September 2016

A teaching of Martin Luther that has had great historical effect is his teaching on vocation. Protesting the Roman Catholic arrangement in which the clergy had callings of higher religious and moral significance than the laity, Luther taught that all Christians have callings or vocations, and that all callings are equal in moral and religious seriousness. They only differ in function. This teaching unleashed unprecedented commitment and energy to worldly work in the Western world. Paralleling his teaching on the priesthood of all believers, Luther taught that all Christians are called by God through Christ to be his beloved and forgiven children, and that they need no mediators to receive that graceful call directly. At the same time, however, Christians who receive that grace through Christ become priests to their neighbors, mediating God’s love through them to the neighbor. They do that very concretely in their vocations. Thus, Christians become conduits of God’s love received through Christ and offered to the neighbor in the various places of responsibility they have been given. For Luther, Christians do not need to cast about for places to exercise their obedience; they were given in the orders of creation into which each Christian was inevitably placed—marriage and family life, work, citizenship, and church. Each person—lay and clergy alike—is called to work in the world. In fulfilling their work gladly and conscientiously, they serve their neighbor. Plain ordinary work is transformed into a Christian vocation as the Christian exercises his faith-active-in-love. Work is no longer simply a job or occupation; it is a calling, a vocation. It is a summons from God. Vocation is also where the Spirit sanctifies the Christian’s life, not in a self-centered quest for perfection, but rather in humble service to the neighbor. While Luther thought there were some occupations that were off-limits to Christians, he accepted most worldly roles as useful to the neighbor. The Christian could be a soldier in a just war and even a hangman in a just cause. One alleged weakness of the classic Lutheran teaching on vocation, however, was that it tended to accept uncritically the roles prescribed by the world. In such teaching, the Christian willingly does what the world prescribes. However, recent Lutheran interpretations of vocation are more dynamic. For example, Gustav Wingren, in Luther on Vocation, argued not only that the orders of creation are dynamic and call for constructive change, but that in Christian vocation the two ways that God reigns in the world intersect. The Christian under the reign of God’s gospel interjects the love liberated by that gospel into one’s worldly occupation, transforming it into a genuine vocation. Love has a transformative effect. It functions critically and constructively. Lutheranism at its best has incorporated more dynamic elements into its great teaching on vocation.
Johannes von Staupitz’s Influence on Martin Luther
Authors: Posset Franz
Published: September 2016

The impact of Johannes von Staupitz (c. 1468–1524) on Martin Luther can hardly be overestimated. Staupitz was elected vicar general of the reformed Augustinian Order in 1503. Between 1504 and 1506 he had the order’s constitutions printed for the first time, which was about the time when Luther became an Augustinian. It is uncertain whether Luther frequently went to Staupitz for confession. However, Luther clearly was a “Staupitzian,” and as such Staupitz sent him from Wittenberg to Rome as the travel companion of the chief negotiator. Upon Luther’s return, he became Staupitz’s successor as professor of biblical theology in Wittenberg. In his preaching Staupitz was celebrated as the “tongue of the Apostle Paul” and the “herald of the gospel,” one who stood up for the evangelical truth. Criticism of indulgences had begun long before Luther’s Ninety-Five Theses or Propositions of 1517. Staupitz and his disciple Luther, in cooperation with their confrère Wenceslaus Linck, spoke up publicly against the indulgences. They composed a text called Treatise on Indulgences, which Luther “edited.” Luther sent his mother a copy of the first edition of Staupitz’s On the Love of God in 1518. As a true Staupitzian Luther gave his endorsement to subsequent editions of that book, which is essentially a book about “grace alone” and “Christ alone” for salvation. In this book Christ’s suffering is “for us,” and God is made sweet and pleasant to us by grace. Staupitz was a Christocentric theologian in following 1 Corinthians 1:23, “We preach nothing else than Christ crucified.” Luther with his “theology of the cross” remained a faithful discipulus of Staupitz. Luther was grateful to Staupitz that the issue of penance had been solved for him, because now penance appeared “sweet” to him and Christ was his “most sweet Savior.” Staupitz and Linck stood by Luther at Augsburg during the encounter with Cardinal Cajetan in 1518. A later letter in which Luther tells about a bad dream in which he felt deserted by his superior does not necessarily demonstrate any change in Staupitz’s attitude toward him. Their friendship and correspondence continued. Staupitz was fully aware of Luther’s admiration for him, which Staupitz cited in his last letter (of April 1, 1524) to Luther, a letter showing that they remained on good terms despite a difference of opinion on monastic vows. Toward the end of his life Luther, in a letter to Elector John Frederick of March 27, 1545, summed up his indebtedness: “Doctor Staupitz is first of all my father in this doctrine and gave birth to me in Christ.”
Law, the U.S. Supreme Court, and Religion
Authors: Davis Derek H.
Published: September 2016

The United States Supreme Court’s religion jurisprudence is typically analyzed based on whether a court’s decision emerges from an Establishment Clause analysis or a Free Exercise Clause analysis. While this method is useful, a more in-depth analysis can be undertaken by identifying various philosophical themes that describe the court’s varied approaches to deciding religion cases. The cases can be analyzed under at least four separate but interrelated themes: separation of church and state, cooperation between sacred and secular activities in religion-based contexts, equal treatment among religions, and the integration of religion and politics. This article examines the High Court’s often controversial decisions affecting religion through the lenses of these four themes.

The term “separation of church and state” is frequently used to describe the American relationship between law and religion, but this term is far too simplistic a description of how church and state interact in the American system; the ways in which the system sometimes embraces separation but sometimes does not, are analyzed and explained.

Consistent with the misconception that the Supreme Court always seeks to “separate” church and state, court analysts will sometimes describe the court’s strategy as giving “no aid” to religion. This also is a simplistic analysis, since it can clearly be shown that the court does not seek to “wall” off religion from government aid in all cases. Rather, the court tends to sanction state support of “secular” activities that arise in religion contexts while denying state aid to the “sacred” components of religious activity. “Equality” is a hallmark of American democracy. While the Founders did not earmark equality as a goal of the religion clauses, the concept has nevertheless emerged as a byproduct of deeper goals, namely sanctioning religious pluralism and providing equal access to government office. If separation of church and state were really the centerpiece of how religion and state activity interact in the United States, the Supreme Court would not sanction the involvement of religion in public debate and discourse, nor would it permit political candidates and officeholders to freely talk about religion in their personal lives and its role in American political life. But the court carefully crafts a jurisprudence that rarely intrudes on this kind of activity. In sum, looking at Supreme Court religion cases through a number of philosophical lenses is a fruitful guide to understanding court decisions that are otherwise often highly complex and confusing.
Civil Rights Movements and Religion in America
Authors: Harvey Paul
Published: September 2016

In the civil rights movement of the mid-20th century, black Christian thought helped to undermine the white supremacist racial system that had governed America for centuries. The civil rights revolution in American history was, to a considerable degree, a religious revolution, one whose social and spiritual impact inspired numerous other movements around the world. Key to the work was a transformation of American religious thought and practice in ways that deftly combined the social gospel and black church traditions, infused with Gandhian notions of active resistance and “soul force,” as well as secular ideas of hardheaded political organizing and the kinds of legal maneuverings that led to the seminal court case of Brown v. Board of Education.

The civil rights movement had legislative aims; it was, to that extent, a political movement. But it was also a religious movement, sustained by the religious power unlocked within southern black churches. The historically racist grounding of whiteness as dominant and blackness as inferior was radically overturned in part through a reimagination of the same Christian thought that was part of creating it in the first place. In similar ways, the Mexican-American farmworkers’ movement drew on the mystic Catholic spirituality of Cesar Chavez and brought to national consciousness the lives and aspirations of an oppressed agricultural proletariat that lacked the most elementary rights of American citizens.

American civil rights movements drew from, and were in part inspired by, the ideas of Mahatma Gandhi and the Indian independence movement. Gandhi’s movement deeply influenced black Americans who visited India from the 1930s to the 1950s and who brought home with them a mixture of ideas and practices deriving from sources as diverse as Gandhi and the 19th-century American progenitor of nonviolent civil disobedience, Henry David Thoreau. American civil rights movements subsequently became a model for any number of freedom movements internationally, notably including the anti-apartheid struggle in South Africa. There, religious figures such as Desmond Tutu became international symbols. Also, the black American freedom struggle based in the American South moved protestors in places as diverse as Czechoslovakia under Soviet domination and Chinese students staring down tanks in Tiananmen Square in 1989.

In the post–civil rights era, some suggested that America had moved into a “post-racial” era, despite the overwhelming statistics documenting racial inequality in American society. Thus, activists who have mined the connection between religion, civil rights, and social justice will have plenty of work to do in the future. The struggle continues through such contemporary venues as the #blacklivesmatter movement.
The Evolution of Modern Jihadism
Authors: Lahoud Nelly
Published: September 2016

Political Islam has generated two ideological strands that use religious ideology to advance their goals, namely, Islamism and jihadism. On the one hand, Islamists have formulated a political paradigm premised on Islamic teachings that are adaptable to the secular framework of the modern state and have, therefore, endured both as domestic and global political actors. On the other hand, jihadis have rejected positive law outright and advanced a global revolutionary paradigm against today’s secular world order. Key to jihadism’s appropriation of Islamic teachings is a quest for a legal code that provides jihadis with both an anti-establishment justification for their violence and a claim to legitimacy in the minds of Muslims whom they wish to enlist as their followers.
Commodities and Consumption in “Golden Age” Argentina
Authors: Elena Eduardo
Published: September 2016

In the late 19th and early 20th centuries, the global trade in commodities forged new economic interconnections and contributed to the emergence of modern ways of life. As one of the leading exporters of temperate goods such as wool, beef, and wheat, Argentina was at the forefront of these trends, and the country underwent remarkable expansion between 1875 and 1913. Although export goods linked Argentina to consumers in Europe and elsewhere, these vital relationships were often obscured by the malleable nature of commodities, the far-flung scope of overseas trade, and the perceived divergence between rural and urban worlds. Within Argentina, similar dynamics were also at work, but commodities became referents in disputes over economic distribution, social inequality, and national development. The tensions between the export sector and an increasingly industrialized and urbanized society geared toward mass consumption raised questions as to how to manage the nation’s wealth—conflicts involving commodities that parallel those of other Latin American societies. By placing the economic history of commodities into conversation with recent research on the social, cultural, and political history of consumption, this article reconsiders Argentina’s “Golden Age” of expansion and its aftermath. The connecting and distancing power of commodities reveals how populations in Argentina and abroad experienced modern capitalism, including its signature transformations of the natural world and everyday life.
Mayan Languages
Authors: England Nora C.
Published: September 2016

Mayan languages are spoken by over 5 million people in Guatemala, Mexico, Belize, and Honduras. There are around 30 different languages today, ranging in size from fairly large (about a million speakers) to very small (fewer than 30 speakers). All Mayan languages are endangered given that at least some children in some communities are not learning the language, and two languages have disappeared since European contact. Mayas developed the most elaborated and most widely attested writing system in the Americas (starting about 300 BC).

The sounds of Mayan languages consist of a voiceless stop and affricate series with corresponding glottalized stops (either implosive and ejective) and affricates, glottal stop, voiceless fricatives (including h in some of them inherited from Proto-Maya), two to three nasals, three to four approximants, and a five vowel system with contrasting vowel length (or tense/lax distinctions) in most languages. Several languages have developed contrastive tone.

The major word classes in Mayan languages include nouns, verbs, adjectives, positionals, and affect words. The difference between transitive verbs and intransitive verbs is rigidly maintained in most languages. They usually use the same aspect markers (but not always). Intransitive verbs only indicate their subjects while transitive verbs indicate both subjects and objects. Some languages have a set of status suffixes which is different for the two classes. Positionals are a root class whose most characteristic word form is a non-verbal predicate. Affect words indicate impressions of sounds, movements, and activities. Nouns have a number of different subclasses defined on the basis of characteristics when possessed, or the structure of compounds. Adjectives are formed from a small class of roots (under 50) and many derived forms from verbs and positionals.

Predicate types are transitive, intransitive, and non-verbal. Non-verbal predicates are based on nouns, adjectives, positionals, numbers, demonstratives, and existential and locative particles. They are distinct from verbs in that they do not take the usual verbal aspect markers. Mayan languages are head marking and verb initial; most have VOA flexible order but some have VAO rigid order. They are morphologically ergative and also have at least some rules that show syntactic ergativity. The most common of these is a constraint on the extraction of subjects of transitive verbs (ergative) for focus and/or interrogation, negation, or relativization. In addition, some languages make a distinction between agentive and non-agentive intransitive verbs. Some also can be shown to use obviation and inverse as important organizing principles. Voice categories include passive, antipassive and agent focus, and an applicative with several different functions.
Speech Perception and Generalization Across Talkers and Accents
Authors: Weatherholtz Kodi , Jaeger T. Florian
Published: September 2016

The seeming ease with which we usually understand each other belies the complexity of the processes that underlie speech perception. One of the biggest computational challenges is that different talkers realize the same speech categories (e.g., /p/) in physically different ways. We review the mixture of processes that enable robust speech understanding across talkers despite this lack of invariance. These processes range from automatic pre-speech adjustments of the distribution of energy over acoustic frequencies (normalization) to implicit statistical learning of talker-specific properties (adaptation, perceptual recalibration) to the generalization of these patterns across groups of talkers (e.g., gender differences).
Community-Based Disaster Risk Reduction
Authors: Shaw Rajib
Published: September 2016

Community-based approaches existed even before the existence of the state and its formal governance structure. People and communities used to help and take care of each other’s disaster needs. However, due to the evolution of state governance, new terminology of community-based disaster risk reduction (CBDRR) has been coined to help communities in an organized way. Different stakeholders are responsible for community-based actions; the two key players are the local governments and civil society, or nongovernment organizations. Private sector and academic and research institutions also play crucial roles in CBDRR. Many innovative CBDRR practices exist in the world, and it is important to analyze them and learn the common lessons. The key to community is its diversity, and this should be kept in mind for the CBDRR. There are different entry points and change agents based on the diverse community. It is important to identify the right change agent and entry point and to develop a sustainable mechanism to institutionalize CBDRR activities. Social networking needs to be incorporated for effective CBDRR.
Correlations of polyploidy and apomixis with elevation and associated environmental gradients in an alpine plant
Authors: Schinkel Christoph C. F. , Kirchheimer Bernhard , Dellinger Agnes S. , Klatt Simone , Winkler Manuela , Dullinger Stefan , Hörandl Elvira
Published: September 2016

Apomictic plants expand their geographical distributions more to higher elevations compared to their sexual progenitors. It was so far unclear whether this tendency is related to mode of reproduction itself or represents a side effect of polyploidy. Apomixis is advantageous for range expansions as no mating partners and pollinators are needed (Baker’s rule). Polyploidy is thought to infer fitness advantages and a higher vigour that would enable plants to adjust better to more extreme climatic conditions. However, little is known about actual performance of plants at higher elevations. We analyzed 81 populations of Ranunculus kuepferi from the whole distribution area in the European Alps to quantify apomictic versus sexual seed formation via flow cytometric seed screening. Seed set and vegetative growth were measured as fitness parameters. All parameters were correlated to geographical distribution, elevation, temperature and precipitation. Flow cytometric seed screening revealed predominantly obligate sexuality (88.9 %) and facultative apomixis in diploid populations, while tetraploid populations are predominantly facultative (65.4 %) to obligate apomictic. Apomictic seed formation correlated significantly to higher elevations, which explains also the observed niche shift to lower temperatures. However, within the tetraploid range, there is no apparent correlation of degree of facultative apomixis to geographical distance. Apomixis appeared in diploids three times independently in separated, otherwise sexual populations in the southwestern refugial areas of the Alps. Diploid apomixis was not successful in range expansions, and obligate sexual polyploids were not observed. Polyploidy may relate to cold tolerance as an adaptation to conditions at high elevations, where diploid sexuals have no fitness advantage. Instead, facultative apomixis may have aided colonization of higher elevations and range expansions in the Alps without mate and pollinator limitation, but did not necessarily involve long-distance dispersal. A direct influence of low temperatures on unreduced gamete formation cannot be ruled out.
Information-optimal genome assembly via sparse read-overlap graphs
Authors: Shomorony Ilan , Kim Samuel H , Courtade Thomas A , Tse David N C
Published: September 2016

Motivation

In the context of third-generation long-read sequencing technologies, read-overlap-based approaches are expected to play a central role in the assembly step. A fundamental challenge in assembling from a read-overlap graph is that the true sequence corresponds to a Hamiltonian path on the graph, and, under most formulations, the assembly problem becomes NP-hard, restricting practical approaches to heuristics. In this work, we avoid this seemingly fundamental barrier by first setting the computational complexity issue aside, and seeking an algorithm that targets information limits. In particular, we consider a basic feasibility question: when does the set of reads contain enough information to allow unambiguous reconstruction of the true sequence?

Results

Based on insights from this information feasibility question, we present an algorithm—the Not-So-Greedy algorithm—to construct a sparse read-overlap graph. Unlike most other assembly algorithms, Not-So-Greedy comes with a performance guarantee: whenever information feasibility conditions are satisfied, the algorithm reduces the assembly problem to an Eulerian path problem on the resulting graph, and can thus be solved in linear time. In practice, this theoretical guarantee translates into assemblies of higher quality. Evaluations on both simulated reads from real genomes and a PacBio Escherichia coli K12 dataset demonstrate that Not-So-Greedy compares favorably with standard string graph approaches in terms of accuracy of the resulting read-overlap graph and contig N50.

Availability

Available at github.com/samhykim/nsg

Contact

courtade@eecs.berkeley.edu or dntse@stanford.edu

Supplementary information

Supplementary data are available at Bioinformatics online.
Assemble CRISPRs from metagenomic sequencing data
Authors: Lei Jikai , Sun Yanni
Published: September 2016

Motivation

Clustered regularly interspaced short palindromic repeats and associated proteins (CRISPR-Cas) allows more specific and efficient gene editing than all previous genetic engineering systems. These exciting discoveries stem from the finding of the CRISPR system being an adaptive immune system that protects the prokaryotes against exogenous genetic elements such as phages. Despite the exciting discoveries, almost all knowledge about CRISPRs is based only on microorganisms that can be isolated, cultured and sequenced in labs. However, about 95% of bacterial species cannot be cultured in labs. The fast accumulation of metagenomic data, which contains DNA sequences of microbial species from natural samples, provides a unique opportunity for CRISPR annotation in uncultivable microbial species. However, the large amount of data, heterogeneous coverage and shared leader sequences of some CRISPRs pose challenges for identifying CRISPRs efficiently in metagenomic data.

Results

In this study, we developed a CRISPR finding tool for metagenomic data without relying on generic assembly, which is error-prone and computationally expensive for complex data. Our tool can run on commonly available machines in small labs. It employs properties of CRISPRs to decompose generic assembly into local assembly. We tested it on both mock and real metagenomic data and benchmarked the performance with state-of-the-art tools.

Availability and Implementation

The source code and the documentation of metaCRISPR is available at https://github.com/hangelwen/metaCRISPR.

Contact

yannisun@msu.edu
Large-scale inference of conjunctive Bayesian networks
Authors: Montazeri Hesam , Kuipers Jack , Kouyos Roger , Böni Jürg , Yerly Sabine , Klimkait Thomas , Aubert Vincent , Günthard Huldrych F , Beerenwinkel Niko ,   The Swiss HIV Cohort Study
Published: September 2016

The continuous time conjunctive Bayesian network (CT-CBN) is a graphical model for analyzing the waiting time process of the accumulation of genetic changes (mutations). CT-CBN models have been successfully used in several biological applications such as HIV drug resistance development and genetic progression of cancer. However, current approaches for parameter estimation and network structure learning of CBNs can only deal with a small number of mutations (<20). Here, we address this limitation by presenting an efficient and accurate approximate inference algorithm using a Monte Carlo expectation-maximization algorithm based on importance sampling. The new method can now be used for a large number of mutations, up to one thousand, an increase by two orders of magnitude. In simulation studies, we present the accuracy as well as the running time efficiency of the new inference method and compare it with a MLE method, expectation-maximization, and discrete time CBN model, i.e. a first-order approximation of the CT-CBN model. We also study the application of the new model on HIV drug resistance datasets for the combination therapy with zidovudine plus lamivudine (AZT + 3TC) as well as under no treatment, both extracted from the Swiss HIV Cohort Study database.

Availability and implementation

The proposed method is implemented as an R package available at https://github.com/cbg-ethz/MC-CBN.

Contact

niko.beerenwinkel@bsse.ethz.ch

Supplementary information

Supplementary data are available at Bioinformatics online.
L 1 regularization facilitates detection of cell type-specific parameters in dynamical systems
Authors: Steiert Bernhard , Timmer Jens , Kreutz Clemens
Published: September 2016

Motivation

A major goal of drug development is to selectively target certain cell types. Cellular decisions influenced by drugs are often dependent on the dynamic processing of information. Selective responses can be achieved by differences between the involved cell types at levels of receptor, signaling, gene regulation or further downstream. Therefore, a systematic approach to detect and quantify cell type-specific parameters in dynamical systems becomes necessary.

Results

Here, we demonstrate that a combination of nonlinear modeling with L1 regularization is capable of detecting cell type-specific parameters. To adapt the least-squares numerical optimization routine to L1 regularization, sub-gradient strategies as well as truncation of proposed optimization steps were implemented. Likelihood-ratio tests were used to determine the optimal regularization strength resulting in a sparse solution in terms of a minimal number of cell type-specific parameters that is in agreement with the data. By applying our implementation to a realistic dynamical benchmark model of the DREAM6 challenge we were able to recover parameter differences with an accuracy of 78%. Within the subset of detected differences, 91% were in agreement with their true value. Furthermore, we found that the results could be improved using the profile likelihood. In conclusion, the approach constitutes a general method to infer an overarching model with a minimum number of individual parameters for the particular models.

Availability and Implementation

A MATLAB implementation is provided within the freely available, open-source modeling environment Data2Dynamics. Source code for all examples is provided online at http://www.data2dynamics.org/.

Contact

bernhard.steiert@fdm.uni-freiburg.de
CoLoRMap: Correcting Long Reads by Mapping short reads
Authors: Haghshenas Ehsan , Hach Faraz , Sahinalp S Cenk , Chauve Cedric
Published: September 2016

Motivation

Second generation sequencing technologies paved the way to an exceptional increase in the number of sequenced genomes, both prokaryotic and eukaryotic. However, short reads are difficult to assemble and often lead to highly fragmented assemblies. The recent developments in long reads sequencing methods offer a promising way to address this issue. However, so far long reads are characterized by a high error rate, and assembling from long reads require a high depth of coverage. This motivates the development of hybrid approaches that leverage the high quality of short reads to correct errors in long reads.

Results

We introduce CoLoRMap, a hybrid method for correcting noisy long reads, such as the ones produced by PacBio sequencing technology, using high-quality Illumina paired-end reads mapped onto the long reads. Our algorithm is based on two novel ideas: using a classical shortest path algorithm to find a sequence of overlapping short reads that minimizes the edit score to a long read and extending corrected regions by local assembly of unmapped mates of mapped short reads. Our results on bacterial, fungal and insect data sets show that CoLoRMap compares well with existing hybrid correction methods.

Availability and Implementation

The source code of CoLoRMap is freely available for non-commercial use at https://github.com/sfu-compbio/colormap

Contact

ehaghshe@sfu.ca or cedric.chauve@sfu.ca

Supplementary information

Supplementary data are available at Bioinformatics online.
LuxGLM: a probabilistic covariate model for quantification of DNA methylation modifications with complex experimental designs
Authors: Äijö Tarmo , Yue Xiaojing , Rao Anjana , Lähdesmäki Harri
Published: September 2016

Motivation

5-methylcytosine (5mC) is a widely studied epigenetic modification of DNA. The ten-eleven translocation (TET) dioxygenases oxidize 5mC into oxidized methylcytosines (oxi-mCs): 5-hydroxymethylcytosine (5hmC), 5-formylcytosine (5fC) and 5-carboxylcytosine (5caC). DNA methylation modifications have multiple functions. For example, 5mC is shown to be associated with diseases and oxi-mC species are reported to have a role in active DNA demethylation through 5mC oxidation and DNA repair, among others, but the detailed mechanisms are poorly understood. Bisulphite sequencing and its various derivatives can be used to gain information about all methylation modifications at single nucleotide resolution. Analysis of bisulphite based sequencing data is complicated due to the convoluted read-outs and experiment-specific variation in biochemistry. Moreover, statistical analysis is often complicated by various confounding effects. How to analyse 5mC and oxi-mC data sets with arbitrary and complex experimental designs is an open and important problem.

Results

We propose the first method to quantify oxi-mC species with arbitrary covariate structures from bisulphite based sequencing data. Our probabilistic modeling framework combines a previously proposed hierarchical generative model for oxi-mC-seq data and a general linear model component to account for confounding effects. We show that our method provides accurate methylation level estimates and accurate detection of differential methylation when compared with existing methods. Analysis of novel and published data gave insights into to the demethylation of the forkhead box P3 (Foxp3) locus during the induced T regulatory cell differentiation. We also demonstrate how our covariate model accurately predicts methylation levels of the Foxp3 locus. Collectively, LuxGLM method improves the analysis of DNA methylation modifications, particularly for oxi-mC species.

Availability and Implementation

An implementation of the proposed method is available under MIT license at https://github.org/tare/LuxGLM/

Contact

taijo@simonsfoundation.org or harri.lahdesmaki@aalto.fi

Supplementary information

Supplementary data are available at Bioinformatics online.
Rail-RNA: scalable analysis of RNA-seq splicing and coverage
Authors: Nellore Abhinav , Collado-Torres Leonardo , Jaffe Andrew E , Alquicira-Hernández José , Wilks Christopher , Pritt Jacob , Morton James , Leek Jeffrey T , Langmead Ben
Published: September 2016

Motivation

RNA sequencing (RNA-seq) experiments now span hundreds to thousands of samples. Current spliced alignment software is designed to analyze each sample separately. Consequently, no information is gained from analyzing multiple samples together, and it requires extra work to obtain analysis products that incorporate data from across samples.

Results

We describe Rail-RNA, a cloud-enabled spliced aligner that analyzes many samples at once. Rail-RNA eliminates redundant work across samples, making it more efficient as samples are added. For many samples, Rail-RNA is more accurate than annotation-assisted aligners. We use Rail-RNA to align 667 RNA-seq samples from the GEUVADIS project on Amazon Web Services in under 16 h for US$0.91 per sample. Rail-RNA outputs alignments in SAM/BAM format; but it also outputs (i) base-level coverage bigWigs for each sample; (ii) coverage bigWigs encoding normalized mean and median coverages at each base across samples analyzed; and (iii) exon–exon splice junctions and indels (features) in columnar formats that juxtapose coverages in samples in which a given feature is found. Supplementary outputs are ready for use with downstream packages for reproducible statistical analysis. We use Rail-RNA to identify expressed regions in the GEUVADIS samples and show that both annotated and unannotated (novel) expressed regions exhibit consistent patterns of variation across populations and with respect to known confounding variables.

Availability and Implementation

Rail-RNA is open-source software available at http://rail.bio.

Supplementary information

Supplementary data are available at Bioinformatics online.
A systematic review of the types and causes of prescribing errors generated from using computerized provider order entry systems in primary and secondary care
Authors: Brown Clare L , Mulcaster Helen L , Triffitt Katherine L , Sittig Dean F , Ash Joan S , Reygate Katie , Husband Andrew K , Bates David W , Slight Sarah P
Published: September 2016

Objective: To understand the different types and causes of prescribing errors associated with computerized provider order entry (CPOE) systems, and recommend improvements in these systems.

Materials and Methods: We conducted a systematic review of the literature published between January 2004 and June 2015 using three large databases: the Cumulative Index to Nursing and Allied Health Literature, Embase, and Medline. Studies that reported qualitative data about the types and causes of these errors were included. A narrative synthesis of all eligible studies was undertaken.

Results: A total of 1185 publications were identified, of which 34 were included in the review. We identified 8 key themes associated with CPOE-related prescribing errors: computer screen display, drop-down menus and auto-population, wording, default settings, nonintuitive or inflexible ordering, repeat prescriptions and automated processes, users’ work processes, and clinical decision support systems. Displaying an incomplete list of a patient’s medications on the computer screen often contributed to prescribing errors. Lack of system flexibility resulted in users employing error-prone workarounds, such as the addition of contradictory free-text comments. Users’ misinterpretations of how text was presented in CPOE systems were also linked with the occurrence of prescribing errors.

Discussion and Conclusions: Human factors design is important to reduce error rates. Drop-down menus should be designed with safeguards to decrease the likelihood of selection errors. Development of more sophisticated clinical decision support, which can perform checks on free-text, may also prevent errors. Further research is needed to ensure that systems minimize error likelihood and meet users’ workflow expectations.