scholarly journals Mutation signatures reveal biological processes in human cancer

2016 ◽  
Author(s):  
Kyle Covington ◽  
Eve Shinbrot ◽  
David A Wheeler
Keyword(s):  
Sparse Matrix ◽  
Human Cancer ◽  
Replication Errors ◽  
Repair Processes ◽  
Relative Contribution ◽  
History Of ◽  
Mutational Processes ◽  
Insight Into ◽  
Mutational Process ◽  
Non Negative Matrix Factorization

Replication errors in the genome accumulate from a variety of mutational processes, which leave a history of mutations on the affected genome. The relative contribution of each mutational process has been characterized by non-negative matrix factorization and has lead to deeper insight into both mutational and repair processes contributing to cancer. However current implementations of NMF have left unresolved some specific patterns that should be present in the mutation data and have not generated signatures designed for classification. Here, we use a variant of NMF, termed non-smooth NMF, to generate sparse matrix factorizations of somatic mutation profiles present in 7129 tumors. nsNMF factorization revealed 21 mutational signatures. We found three APOBEC mutational processes clearly segregating with the published APOBEC enzymology and trans-lesion repair processes. We discovered several signatures differed between geographic locations even between closely related tissues.

scholarly journals Mutational signatures associated with tobacco smoking in human cancer

2016 ◽  
Author(s):  
Ludmil B. Alexandrov ◽  
Young Seok Ju ◽  
Kerstin Haase ◽  
Peter Van Loo ◽  
Iñigo Martincorena ◽  
...  
Keyword(s):  
Tobacco Smoke ◽  
Tobacco Smoking ◽  
Human Cancer ◽  
Mutational Signatures ◽  
Cytidine Deaminases ◽  
Endogenous Clock ◽  
Cancer Types ◽  
Tobacco Carcinogens ◽  
Mutational Processes ◽  
Mutational Process

ABSTRACTTobacco smoking increases the risk of at least 15 classes of cancer. We analyzed somatic mutations and DNA methylation in 5,243 cancers of types for which tobacco smoking confers an elevated risk. Smoking is associated with increased mutation burdens of multiple distinct mutational signatures, which contribute to different extents in different cancers. One of these signatures, mainly found in cancers derived from tissues directly exposed to tobacco smoke, is attributable to misreplication of DNA damage caused by tobacco carcinogens. Others likely reflect indirect activation of DNA editing by APOBEC cytidine deaminases and of an endogenous clock-like mutational process. The results are consistent with the proposition that smoking increases cancer risk by increasing the somatic mutation load, although direct evidence for this mechanism is lacking in some smoking-related cancer types.ONE SENTENCE SUMMARYMultiple distinct mutational processes associate with tobacco smoking in cancer reflecting direct and indirect effects of tobacco smoke.

scholarly journals Hidden Markov Models Lead to Higher Resolution Maps of Mutation Signature Activity in Cancer

2018 ◽  
Author(s):  
Xiaoqing Huang ◽  
Itay Sason ◽  
Damian Wojtowicz ◽  
Yoo-Ah Kim ◽  
Mark D.M. Leiserson ◽  
...  
Keyword(s):  
Markov Models ◽  
Hidden Markov ◽  
Biological Knowledge ◽  
Sequential Dependencies ◽  
Replication Time ◽  
Tumor Level ◽  
Genomic Regions ◽  
Mutational Processes ◽  
Insight Into ◽  
Mutational Process

AbstractKnowing the activity of the mutational processes shaping a cancer genome may provide insight into tumorigenesis and personalized therapy. It is thus important to uncover the characteristic signatures of active mutational processes in patients from their patterns of single base substitutions. However, mutational processes do not act uniformly on the genome and are biased by factors such as the genome’s chromatin structure or replication origins. These factors may lead to statistical dependencies among neighboring mutations, calling for modeling approaches that can account for such dependencies to better estimate mutational process activities.Here we develop the first sequence-dependent models for mutation signatures. We apply these models to characterize genomic and other factors that influence the activity of previously validated mutation signatures in breast cancer. We find that our tool, SigMa, can accurately assign genomic mutations to mutation signatures, yielding assignments that are of higher likelihood than those obtained with models that assume independence between signatures and align better with current biological knowledge. Our analysis resolves a controversy related to the dependency of APOBEC signatures on replication time and links Signatures 18 and 30 to oxidative damage.Modeling the sequential dependencies of mutation signatures leads to improved estimates of mutation signature activity both at the tumor-level and within specific genomic regions, yielding higher resolution maps of mutation signature activity in cancer.

The Subaltern Speak- A Study On The Culture Of The Arunachalis With Special Reference To Mamang Dai’s The Legends Of Pensam

2019 ◽  
Vol 5 (4) ◽  
pp. 14-20
Author(s):  
Ms. Cheryl Antonette Dumenil ◽  
Dr. Cheryl Davis
Keyword(s):  
Special Reference ◽  
Small World ◽  
Natural World ◽  
Arunachal Pradesh ◽  
North East India ◽  
North East ◽  
Shared History ◽  
History Of ◽  
And Gender ◽  
Insight Into

North- East India is an under veiled region with an awe-inspiring landscape, different groups of ethnic people, their culture and heritage. Contemporary writers from this region aspire towards a vision outside the tapered ethnic channel, and they represent a shared history. In their writings, the cultural memory is showcased, and the intensity of feeling overflows the labour of technique and craft. Mamang Dai presents a rare glimpse into the ecology, culture, life of the tribal people and history of the land of the dawn-lit mountains, Arunachal Pradesh, through her novel The Legends of Pensam. The word ‘Pensam’ in the title means ‘in-between’,  but it may also be interpreted as ‘the hidden spaces of the heart’. This is a small world where anything can happen. Being adherents of the animistic faith, the tribes here believe in co-existence with the natural world along with the presence of spirits in their forests and rivers. This paper attempts to draw an insight into the culture and gender of the Arunachalis with special reference to The Legends of Pensam by Mamang Dai.

Collected Documents on the History of the Pskov Orthodox Mission: A Recent Publication

2018 ◽  
pp. 306-312
Author(s):  
Veniamin F. Zima ◽  
Keyword(s):  
Personal Data ◽  
Prisoners Of War ◽  
Inner Life ◽  
Great Patriotic War ◽  
Occupied Territories ◽  
History Of ◽  
Underground Resistance ◽  
The Baltic ◽  
The Church ◽  
Insight Into

The reviewed work is devoted to a significant, and yet little-studied in both national and foreign scholarship, issue of the clergy interactions with German occupational authorities on the territory of the USSR in the days of the Great Patriotic War. It introduces into scientific use historically significant complex of documents (1941-1945) from the archive of the Office of the Metropolitan Sergius (Voskresensky) of Vilnius and Lithuania, patriarchal exarch in Latvia and Estonia, and also records from the investigatory records on charges against clergy and employees concerned in the activities of the Pskov Orthodox Mission (1944-1990). Documents included in the publication are stored in the archives of Moscow, St. Petersburg, Estonia, Lithuania, Leningrad, Novgorod, and Pskov regions. They allow some insight into nature, forms, and methods of the Nazi occupational regime policies in the conquered territories (including policies towards the Church). The documents capture religious policies of the Nazis and inner life of the exarchate, describe actual situation of population and clergy, management activities and counterinsurgency on the occupied territories. The documents bring to light connections between the exarchate and German counterintelligence and reveal the nature of political police work with informants. They capture the political mood of population and prisoners of war. There is information on participants of partisan movement and underground resistance, on communication net between the patriarchal exarchate in the Baltic states and the German counterintelligence. Reports and dispatches of the clergy in the pay of the Nazis addressed to the Metropolitan Sergius (Voskresensky) contain detailed activity reports. Investigatory records contain important biographical information and personal data on the collaborators. Most of the documents, being classified, have never been published before.

Prostate Carcinogenesis: Insights in relation to Epigenetics and Inflammation.

2020 ◽  
Vol 20 ◽  
Author(s):  
Mirazkar D. Pandareesh ◽  
Vivek Hamse Kameshwar ◽  
Kullaiah K. Byrappa
Keyword(s):  
Prostate Cancer ◽  
Epithelial Mesenchymal Transition ◽  
Human Cancer ◽  
Control Cell ◽  
Diagnosis And Treatment ◽  
Epigenetic Changes ◽  
Mesenchymal Transition ◽  
Prostate Carcinogenesis ◽  
History Of ◽  
Clinical Potential

: Prostate cancer is a multifactorial disease that mainly occurs due to the accumulation of somatic, genetic and epigenetic changes, resulting in the inactivation of tumor-suppressor genes and activation of oncogenes. Mutations in genes, specifically those that control cell growth and division or the repair of damaged DNA, make the cells grow and divide uncontrollably to form a tumor. The risk of developing prostate cancer depends upon the gene that has undergone the mutation. Identifying such genetic risk factors for prostate cancer pose a challenge for the researchers. Besides genetic mutations, many epigenetic alterations including DNA methylation, histone modifications (methylation, acetylation, ubiquitylation, sumoylation, and phosphorylation) nucleosomal remodelling, and chromosomal looping, have been significantly contributed to the onset of prostate cancer as well as the prognosis, diagnosis, and treatment of prostate cancer. Chronic inflammation also plays a major role in the onset and progression of human cancer, via. modifications in the tumor microenvironment by initiating epithelial-mesenchymal transition and remodelling the extracellular matrix. In this article, the authors present a brief history of the mechanisms and potential links between the genetic aberrations, epigenetic changes, inflammation and inflammasomes that are known to contribute to the prognosis of prostate cancer. Furthermore, the authors examine and discuss clinical potential of prostate carcinogenesis in relation to epigenetics and inflammation for its diagnosis and treatment.

The History of the Judahite Bench Tomb

2018 ◽  
Author(s):  
Matthew Suriano
Keyword(s):  
Iron Age ◽  
Hebrew Bible ◽  
Cultural Practices ◽  
Seventh Century ◽  
Mortuary Practices ◽  
Iron Age Ii ◽  
Gradual Development ◽  
History Of ◽  
The Dead ◽  
Insight Into

The history of the Judahite bench tomb provides important insight into the meaning of mortuary practices, and by extension, death in the Hebrew Bible. The bench tomb appeared in Judah during Iron Age II. Although it included certain burial features that appear earlier in the Middle and Late Bronze Ages, such as burial benches, and the use of caves for extramural burials, the Judahite bench tomb uniquely incorporated these features into a specific plan that emulated domestic structures and facilitated multigenerational burials. During the seventh century, and continuing into the sixth, the bench tombs become popular in Jerusalem. The history of this type of burial shows a gradual development of cultural practices that were meant to control death and contain the dead. It is possible to observe within these cultural practices the tomb as a means of constructing identity for both the dead and the living.

Galileo Unbound

2018 ◽  
Author(s):  
David D. Nolte
Keyword(s):  
Free Fall ◽  
The Sun ◽  
Quantum Field ◽  
Many Worlds ◽  
Quantum Particles ◽  
Light Rays ◽  
History Of ◽  
And Control ◽  
The Universe ◽  
Insight Into

Galileo Unbound: A Path Across Life, The Universe and Everything traces the journey that brought us from Galileo’s law of free fall to today’s geneticists measuring evolutionary drift, entangled quantum particles moving among many worlds, and our lives as trajectories traversing a health space with thousands of dimensions. Remarkably, common themes persist that predict the evolution of species as readily as the orbits of planets or the collapse of stars into black holes. This book tells the history of spaces of expanding dimension and increasing abstraction and how they continue today to give new insight into the physics of complex systems. Galileo published the first modern law of motion, the Law of Fall, that was ideal and simple, laying the foundation upon which Newton built the first theory of dynamics. Early in the twentieth century, geometry became the cause of motion rather than the result when Einstein envisioned the fabric of space-time warped by mass and energy, forcing light rays to bend past the Sun. Possibly more radical was Feynman’s dilemma of quantum particles taking all paths at once—setting the stage for the modern fields of quantum field theory and quantum computing. Yet as concepts of motion have evolved, one thing has remained constant, the need to track ever more complex changes and to capture their essence, to find patterns in the chaos as we try to predict and control our world.

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