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The revolutionary progress in development of next-generation sequencing (NGS) technologies has made it possible to deliver accurate genomic information in a timely manner. Over the past several years, NGS has transformed biomedical and clinical research and found its application in the field of personalized medicine. Here we discuss the rise of personalized medicine and the history of NGS. We discuss current applications and uses of NGS in medicine, including infectious diseases, oncology, genomic medicine, and dermatology. We provide a brief discussion of selected studies where NGS was used to respond to wide variety of questions in biomedical research and clinical medicine. Finally, we discuss the challenges of implementing NGS into routine clinical use., (© 2025. The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature.)

Recent developments have revolutionized the study of biomolecules. Among them are molecular markers, amplification and sequencing of nucleic acids. The latter is classified into three generations. The first allows to sequence small DNA fragments. The second one increases throughput, reducing turnaround and pricing, and is therefore more convenient to sequence full genomes and transcriptomes. The third generation is currently pushing technology to its limits, being able to sequence single molecules, without previous amplification, which was previously impossible. Besides, this represents a new revolution, allowing researchers to directly sequence RNA without previous retrotranscription. These technologies are having a significant impact on different areas, such as medicine, agronomy, ecology and biotechnology. Additionally, the study of biomolecules is revealing interesting evolutionary information. That includes deciphering what makes us human, including phenomena like non-coding RNA expansion. All this is redefining the concept of gene and transcript. Basic analyses and applications are now facilitated with new genome editing tools, such as CRISPR. All these developments, in general, and nucleic-acid sequencing, in particular, are opening a new exciting era of biomolecule analyses and applications, including personalized medicine, and diagnosis and prevention of diseases for humans and other animals.

The past 50 years has been the greatest era of plant science discovery, and most of the discoveries have emerged from or been facilitated by our knowledge of plant chromosomes. At last we have descriptive and mechanistic outlines of the information in chromosomes that programs plant life. We had almost no such information 50 years ago when few had isolated DNA from any plant species. The important features of genes have been revealed through whole genome comparative genomics and testing of variants using transgenesis. Progress has been enabled by the development of technologies that had to be invented and then become widely available. Arabidopsis (Arabidopsis thaliana) and rice (Oryza sativa) have played extraordinary roles as model species. Unexpected evolutionary dramas were uncovered when learning that chromosomes have to manage constantly the vast numbers of potentially mutagenic families of transposons and other repeated sequences. The chromatin-based transcriptional and epigenetic mechanisms that co-evolved to manage the evolutionary drama as well as gene expression and 3-D nuclear architecture have been elucidated these past 20 years. This perspective traces some of the major developments with which I have become particularly familiar while seeking ways to improve crop plants. I draw some conclusions from this look-back over 50 years during which the scientific community has (i) exposed how chromosomes guard, readout, control, recombine, and transmit information that programs plant species, large and small, weed and crop, and (ii) modified the information in chromosomes for the purposes of genetic, physiological, and developmental analyses and plant improvement., (© The Author(s) 2021. Published by Oxford University Press on behalf of American Society of Plant Biologists.)

In this minireview, we provide a historical outline of the events that led to the identification and characterization of the deiodinases, the recognition that deiodination plays a major role in thyroid hormone action, and the cloning of the 3 deiodinase genes. The story starts in 1820, when it was first determined that elemental iodine was important for normal thyroid function. Almost 100 years later, it was found that the primary active principle of the gland, T4, contains iodine. Once radioactive iodine became available in the 1940s, it was demonstrated that the metabolism of T4 included deiodination, but at the time it was assumed to be merely a degradative process. However, this view was questioned after the discovery of T3 in 1952. We discuss in some detail the events of the next 20 years, which included some failures followed by the successful demonstration that deiodination is indeed essential to normal thyroid hormone action. Finally, we describe how the 3 deiodinases were identified and characterized and their genes cloned., (© The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

John Sulston changed the way we do science, not once, but three times - initially with the complete cell lineage of the nematode Caenorhabditis elegans , next with completion of the genome sequences of the worm and human genomes and finally with his strong and active advocacy for open data sharing. His contributions were widely recognized and in 2002 he received the Nobel Prize in Physiology and Medicine.

Without question, molecular biology drives modern neuroscience. The past 50 years has been nothing short of revolutionary as key findings have moved the field from correlation toward causation. Most obvious are the discoveries and strategies that have been used to build tools for visualizing circuits, measuring activity, and regulating behavior. Less flashy, but arguably as important are the myriad investigations uncovering the actions of single molecules, macromolecular structures, and integrated machines that serve as the basis for constructing cellular and signaling pathways identified in wide-scale gene or RNA studies and for feeding data into informational networks used in systems biology. This review follows the pathways that were opened in neuroscience by major discoveries and set the stage for the next 50 years., (Copyright © 2020 the authors.)

DNA sequencing has been characterised by scholars and life scientists as an example of 'big', 'fast' and 'automated' science in biology. This paper argues, however, that these characterisations are a product of a particular interpretation of what sequencing is, what I call 'thin sequencing'. The 'thin sequencing' perspective focuses on the determination of the order of bases in a particular stretch of DNA. Based upon my research on the pig genome mapping and sequencing projects, I provide an alternative 'thick sequencing' perspective, which also includes a number of practices that enable the sequence to travel across and be used in wider communities. If we take sequencing in the thin manner to be an event demarcated by the determination of sequences in automated sequencing machines and computers, this has consequences for the historical analysis of sequencing projects, as it focuses attention on those parts of the work of sequencing that are more centralised, fast (and accelerating) and automated. I argue instead that sequencing can be interpreted as a more open-ended process including activities such as the generation of a minimum tile path or annotation, and detail the historiographical and philosophical consequences of this move., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Genome data, the core of the 2008 proclaimed big data revolution in biology, are automatically generated and analyzed. The transition from the manual laboratory practice of electrophoresis sequencing to automated DNA-sequencing machines and software-based analysis programs was completed between 1982 and 1992. This transition facilitated the first data deluge, which was considerably increased by the second and third generation of DNA-sequencers during the 2000s. However, the strategies for evaluating sequence data were also transformed along with this transition. The paper explores both the computational strategies of automation, as well as the data evaluation culture connected with it, in order to provide a complete picture of the complexity of today's data generation and its intrinsic data positivism. This paper is thereby guided by the question, whether this data positivism is the basis of the big data revolution of molecular biology announced today, or it marks the beginning of its data hubris.

This review commemorates the 40th anniversary of DNA sequencing, a period in which we have already witnessed multiple technological revolutions and a growth in scale from a few kilobases to the first human genome, and now to millions of human and a myriad of other genomes. DNA sequencing has been extensively and creatively repurposed, including as a 'counter' for a vast range of molecular phenomena. We predict that in the long view of history, the impact of DNA sequencing will be on a par with that of the microscope.

From 1987 and during the following 20 years, a few research teams exploring bacteria and archea genome sequences uncover the prokaryotic adaptative immune system made of the CRISPR sequence and associated cas genes. First believed to be similar to the eukaryote RNA interference system, CRISPR-Cas turned out to be unique and of an amazing genetic complexity. The comparative studies of CRISPR arrays and of cas, and later of microbiotes metagenomes allowed to propose an evolution scenario for these systems. The results demonstrate the importance of a naturalistic approach, without a priori, for the understanding of living organisms., (© Société de Biologie, 2018.)

Determining the order of nucleic acid residues in biological samples is an integral component of a wide variety of research applications. Over the last fifty years large numbers of researchers have applied themselves to the production of techniques and technologies to facilitate this feat, sequencing DNA and RNA molecules. This time-scale has witnessed tremendous changes, moving from sequencing short oligonucleotides to millions of bases, from struggling towards the deduction of the coding sequence of a single gene to rapid and widely available whole genome sequencing. This article traverses those years, iterating through the different generations of sequencing technology, highlighting some of the key discoveries, researchers, and sequences along the way., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Twenty years ago, the publication of the first bacterial genome sequence, from Haemophilus influenzae, shook the world of bacteriology. In this Timeline, we review the first two decades of bacterial genome sequencing, which have been marked by three revolutions: whole-genome shotgun sequencing, high-throughput sequencing and single-molecule long-read sequencing. We summarize the social history of sequencing and its impact on our understanding of the biology, diversity and evolution of bacteria, while also highlighting spin-offs and translational impact in the clinic. We look forward to a 'sequencing singularity', where sequencing becomes the method of choice for as-yet unthinkable applications in bacteriology and beyond.

Echinoderm genome sequences are a corpus of useful information about a clade of animals that serve as research models in fields ranging from marine ecology to cell and developmental biology. Genomic information from echinoids has contributed to insights into the gene interactions that drive the developmental process at the molecular level. Such insights often rely heavily on genomic information and the kinds of questions that can be asked thus depend on the quality of the sequence information. Here we describe the history of echinoderm genomic sequence assembly and present details about the quality of the data obtained. All of the sequence information discussed here is posted on the echinoderm information web system, Echinobase.org., (Copyright © 2015 Elsevier B.V. All rights reserved.)

The Genetics Society of America's George W. Beadle Award honors individuals who have made outstanding contributions to the community of genetics researchers and who exemplify the qualities of its namesake as a respected academic, administrator, and public servant. The 2015 recipient is John Postlethwait. He has made groundbreaking contributions in developing the zebrafish as a molecular genetic model and in understanding the evolution of new gene functions in vertebrates. He built the first zebrafish genetic map and showed that its genome, along with that of distantly related teleost fish, had been duplicated. Postlethwait played an integral role in the zebrafish genome-sequencing project and elucidated the genomic organization of several fish species. Postlethwait is also honored for his active involvement with the zebrafish community, advocacy for zebrafish as a model system, and commitment to driving the field forward., (Copyright © 2015 by the Genetics Society of America.)

One late afternoon in the beginning of January 1986, bicycling from the lab over the hill to the small village of Fulbourn, the idea for an alternative DNA sequencing technique came to my mind. The basic concept was to follow the activity of DNA polymerase during nucleotide incorporation into a DNA strand by analyzing the pyrophosphate released during the process. Today, the technique is used in multidisciplinary fields in academic, clinical, and industrial settings all over the word. This technique can be used for both single-base sequencing and whole-genome sequencing, depending on the format used.In this chapter, I give my personal account of the development of Pyrosequencing(®)-beginning on a winter day in 1986, when I first envisioned the method-until today, nearly 30 years later.

The development of mass spectrometric methods in peptide and protein chemistry in the author's laboratory is reviewed, from the first determination of the amino acid sequence of small peptides in the late 1950s to its use for the determination of the primary structure of large proteins by a combination of mass spectrometry and DNA sequencing in the late 1980s. This article is part of a Special Issue entitled: 20years of Proteomics in memory of Viatliano Pallini. Guest Editors: Luca Bini, Juan J. Calvete, Natacha Turck, Denis Hochstrasser and Jean-Charles Sanchez., (Copyright © 2014 Elsevier B.V. All rights reserved.)

The concept of 'Fifth Business' is used to analyze a minority standpoint and bring serious attention to the role of scientists who play a galvanizing role in a science but for multiple reasons appear less prominently in more common recounts of any particular development. Biochemist Ray Wu (1928-2008) published a DNA sequencing experiment in March 1970 using DNA polymerase catalysis and specific nucleotide labeling, both of which are foundational to general sequencing methods today. The scant mention of Wu's work from textbooks, research articles, and other accounts of DNA sequencing calls into question how scientific collective memory forms. This alternative history seeks to understand why a key figure in nucleic acid sequence analysis has remained less visibly connected or peripheral to solidifying narratives about the history of DNA sequencing. The study resists predictable dismissals of Wu's work in order to seriously examine the formation of his nucleic acid sequence analysis research program and how he shared his knowledge of sequencing during a period of rapid advancement in the field. An analysis of Wu's work on sequencing the cohesive ends of lambda bacteriophage in the 1960s and 1970s exemplifies how a variety of individuals and groups attempted to develop protocol for sequencing the order of nucleotide base pairs comprising DNA. This historical examination of the sociality of scientific research suggests a way to understand how Wu and others contributed to the very collective memory of DNA sequencing that Wu eventually tried to repair. The study of Wu, who was a Chinese immigrant to the United States, provides a foundation for further critical scholarship on the heterogeneous histories of Asian American bioscientists, the sociality of their scientific works, and how the resulting knowledge produced is preserved, if not evenly, in a scientific field's collective memory., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Genomics is a relatively new scientific discipline, having DNA sequencing as its core technology. As technology has improved the cost and scale of genome characterization over sequencing's 40-year history, the scope of inquiry has commensurately broadened. Massively parallel sequencing has proven revolutionary, shifting the paradigm of genomics to address biological questions at a genome-wide scale. Sequencing now empowers clinical diagnostics and other aspects of medical care, including disease risk, therapeutic identification, and prenatal testing. This Review explores the current state of genomics in the massively parallel sequencing era., (Copyright © 2013 Elsevier Inc. All rights reserved.)

Nucleic acid sequencing is the mainstay of biological research. There are several generations of DNA sequencing technologies that can be well characterized through their nature and the kind of output they provide. Dideoxy terminator sequencing developed by Sanger dominated for 30 years and was the workhorse used for the Human Genome Project. In 2005 the first 2nd generation sequencer was presented with an output orders of magnitude higher than Sanger sequencing and dramatically decreased cost. We are now at the dawn of 3rd generation with nanopore systems that are being developed for DNA sequencing. Meanwhile the field is also broadening into applications that complement 1st, 2nd and 3rd generation sequencing systems to get high resolution genetic information. The REvolutionary Approaches and Devices for Nucleic Acid analysis (READNA) consortium funded by the European Commission under FP7 has made great contributions to the development of new nucleic acid analysis methodology., (Copyright © 2012 Elsevier B.V. All rights reserved.)

DNA sequencing using reversible terminators, as one sequencing by synthesis strategy, has garnered a great deal of interest due to its popular application in the second-generation high-throughput DNA sequencing technology. In this review, we provided its history of development, classification, and working mechanism of this technology. We also outlined the screening strategies for DNA polymerases to accommodate the reversible terminators as substrates during polymerization; particularly, we introduced the "REAP" method developed by us. At the end of this review, we discussed current limitations of this approach and provided potential solutions to extend its application., (Copyright © 2013. Production and hosting by Elsevier Ltd.)

Model organisms became an indispensable part of experimental systems in molecular developmental and cell biology, constructed to investigate physiological and pathological processes. They are thought to play a crucial role for the elucidation of gene function, complementing the sequencing of the genomes of humans and other organisms. Accordingly, historians and philosophers paid considerable attention to various issues concerning this aspect of experimental biology. With respect to the representational features of model organisms, that is, their status as models, the main focus was on generalization of phenomena investigated in such experimental systems. Model organisms have been said to be models for other organisms or a higher taxon. This, however, presupposes a representation of the phenomenon in question. I will argue that prior to generalization, model organisms allow researchers to built generative material models of phenomena - structures, processes or the mechanisms that explain them - through their integration in experimental set-ups that carve out the phenomena from the whole organism and thus represent them. I will use the history of zebrafish biology to show how model organism systems, from around 1970 on, were developed to construct material models of molecular mechanisms explaining developmental or physiological processes., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

This detailed review provides a history and update of the complex field of cancer genetics. Using examples of progress such as the development of imatinib for chronic myeloid leukemia (which stemmed from the recognition of the Philadelphia chromosome in the 1960s), Michael Stratton, Director of the Sanger Institute in Cambridge is confident that we are now entering the end game of cancer genome sequencing. This has led to other drug therapies, based on knowledge of the molecular changes in some cancers, lung and breast cancers for example.

The sequence of the human genome has dramatically accelerated biomedical research. Here I explore its impact, in the decade since its publication, on our understanding of the biological functions encoded in the genome, on the biological basis of inherited diseases and cancer, and on the evolution and history of the human species. I also discuss the road ahead in fulfilling the promise of genomics for medicine.

In the past ten years the development of next generation sequencing technologies brought a new era in the field of quick and efficient DNA sequencing. In our study we give an overview of the methodological achievements from Sanger's chain-termination sequencing in 1975 to those allowing real-time DNA sequencing today. Sequencing methods that utilize clonal amplicons for parallel multistrand sequencing comprise the basics of currently available next generation sequencing techniques. Nowadays next generation sequencing is mainly used for basic research in functional genomics, providing quintessential information in the meta-analyses of data from signal transduction pathways, onthologies, proteomics and metabolomics. Although next generation sequencing is yet sparsely used in clinical practice, cardiology, oncology and epidemiology already show an immense need for the additional knowledge obtained by this new technology. The main barrier of its spread is the lack of standardization of analysis evaluation methods, which obscure objective assessment of the results.

Contemporary culture views DNA through a strange temporal logic: on the one hand, technologies of DNA identification and sequencing testify to fundamental transformations in the way we understand biology, anthropology, law, and medicine—we live in "the DNA age"; and on the other, these technologies have revealed as much about the past as they have about the present or future, gesturing backwards to scenes of conception, crime, and evolutionary branching. The essay shows how this double temporal logic operates within William Gibson's electronic poem Agrippa. It concludes that the poem's stanzas form a metaphorical DNA fingerprint that reveals Gibson's life to be, paradoxically, a novel repetition of his father's and grandfather's lives.

Eric Davidson's work from 1969-2006 illustrates a period in the study of gene regulation that marked a transition from the gene to the genome and from theory-driven to data-intensive science. To make sense of this transition, I address Davidson's work during a first, predominantly theoretical, episode and contrast it with a later chapter in his research devoted to sequencing the California purple sea urchin genome and, more recently, to the computerized analysis of sea urchin development. By comparing these two approaches I offer some thoughts on how work configuration and material organization in the study of metazoan gene regulation have changed over the past forty years.

The dialectic discourse of the 'gene' as the unit of heredity deduced from the phenotype, whether an intervening variable or a hypothetical construct, appeared to be settled with the presentation of the molecular model of DNA: the gene was reduced to a sequence of DNA that is transcribed into RNA that is translated into a polypeptide; the polypeptides may fold into proteins that are involved in cellular metabolism and structure, and hence function. This path turned out to be more bewildering the more the regulation of products and functions were uncovered in the contexts of integrated cellular systems. Philosophers struggling to define a unified concept of the gene as the basic entity of (molecular) genetics confronted those who suggested several different 'genes' according to the conceptual frameworks of the experimentalists. Researchers increasingly regarded genes de facto as generic terms for describing their empiric data, and with improved DNA-sequencing capacities these entities were as a rule bottom-up nucleotide sequences that determine functions. Only recently did empiricists return to discuss conceptual considerations, including top-down definitions of units of function that through cellular mechanisms select the DNA sequences which comprise 'genomic-footprints' of functional entities., (Copyright © 2010 Elsevier Ltd. All rights reserved.)

Fred Sanger, the inventor of the first protein, RNA and DNA sequencing methods, has traditionally been seen as a technical scientist, engaged in laboratory bench work and not interested at all in intellectual debates in biology. In his autobiography and commentaries by fellow researchers, he is portrayed as having a trajectory exclusively dependent on technological progress. The scarce historical scholarship on Sanger partially challenges these accounts by highlighting the importance of professional contacts, institutional and disciplinary moves in his career, spanning from 1940 to 1983. This paper will complement such literature by focusing, for the first time, on the transition of Sanger's sequencing strategies from degrading to copying the target molecule, which occurred in the late 1960s as he was shifting from protein and RNA to DNA sequencing, shortly after his move from the Department of Biochemistry to the Laboratory of Molecular Biology, both based in Cambridge (U.K.). Through a reinterpretation of Sanger's papers and retrospective accounts and a pioneering investigation of his laboratory notebooks, I will claim that sequencing shifted from the working procedures of organic chemistry to those of the emergent molecular biology. I will also argue that sequencing deserves a history in its own right as a practice and not as a technique subordinated to the development of molecular biology or genomics. My proposed history of sequencing leads to a reappraisal of current STS debates on bioinformatics, biotechnology and biomedicine.

FASTQ has emerged as a common file format for sharing sequencing read data combining both the sequence and an associated per base quality score, despite lacking any formal definition to date, and existing in at least three incompatible variants. This article defines the FASTQ format, covering the original Sanger standard, the Solexa/Illumina variants and conversion between them, based on publicly available information such as the MAQ documentation and conventions recently agreed by the Open Bioinformatics Foundation projects Biopython, BioPerl, BioRuby, BioJava and EMBOSS. Being an open access publication, it is hoped that this description, with the example files provided as Supplementary Data, will serve in future as a reference for this important file format.

Sequencing of human and other genomes has been at the center of interest in the biomedical field over the past several decades and is now leading toward an era of personalized medicine. During this time, DNA-sequencing methods have evolved from the labor-intensive slab gel electrophoresis, through automated multiCE systems using fluorophore labeling with multispectral imaging, to the "next-generation" technologies of cyclic-array, hybridization based, nanopore and single molecule sequencing. Deciphering the genetic blueprint and follow-up confirmatory sequencing of Homo sapiens and other genomes were only possible with the advent of modern sequencing technologies that were a result of step-by-step advances with a contribution of academics, medical personnel and instrument companies. While next-generation sequencing is moving ahead at breakneck speed, the multicapillary electrophoretic systems played an essential role in the sequencing of the Human Genome, the foundation of the field of genomics. In this prospective, we wish to overview the role of CE in DNA sequencing based in part of several of our articles in this journal.

DNA, one of the most famous molecules is 140-years-old. Its history has engaged three centuries of experiments, leading us to a point, where the Homo sapiens genome sequence is known. The "DNA breakthrough" is dated on 1953, when James Watson and Francis Crick proposed the model of molecular structure of DNA. But the origin of that great achievement goes back to 1869 and early efforts of Friedrich Miescher, the Swiss doctor, who isolated DNA (than termed nuclein) for the first time. Since that time wealth information on "nuclein", its functions, structure and usage has been collected and formed a basis for modern molecular biology, chemical biology and biotechnology. This article describes the events and circumstances of the most important DNA discoveries since its first isolation up to completing the human genome project and deep DNA sequencing techniques application.

Much of our understanding of human physiology, and of many aspects of pathology, has its antecedents in laboratory and clinical studies of hemoglobin. Over the last century, knowledge of the genetics, functions, and diseases of the hemoglobin proteins has been refined to the molecular level by analyses of their crystallographic structures and by cloning and sequencing of their genes and surrounding DNA. In the last few decades, research has opened up new paradigms for hemoglobin related to processes such as its role in the transport of nitric oxide and the complex developmental control of the alpha-like and beta-like globin gene clusters. It is noteworthy that this recent work has had implications for understanding and treating the prevalent diseases of hemoglobin, especially the use of hydroxyurea to elevate fetal hemoglobin in sickle cell disease. It is likely that current research will also have significant clinical implications, as well as lessons for other aspects of molecular medicine, the origin of which can be largely traced to this research tradition.

The procedures that allow identification have evolved during the time inevitably, as a consequence of ever new technologies that can simplify and widen their own application. Nevertheless, it is interesting to focus the attention on how, although time goes by and the use of complex tools, these techniques are based on principles already used by our predecessors and able to resist to the changes imposed by our age. Indeed, if DNA studies can be considered to be recent discovery, the other identification techniques find their reason in past ages; for example dactyloscopy science, identification through bones, forensic odontology that represent milestones of this discipline. Our study underlines that a few aspect of this science have been completely abandoned, some of them are used in the recent identification inquires, other represent a milestone in the development of this science.