Your Ads Privacy ChoicesIMDb Text description provided by the architects. The Brazilian architecture office Biselli Katchborian Arquitetos, led by the architects Artur Katchborian and Mario Biselli, is responsible for the new retrofit and expansion project of Etapa School, in a building originally designed in 1984 by the Brazilian architect Paulo Bastos in São Paulo (Brazil).  In addition to the search for new natural light entrances, better clarity, and good institutional communication, the proposal took advantage of the 15 meters gap between Palestina Street and Mascote Avenue (located on the east side of the town) to create two accesses. The project program school consists of 2 blocks, with the largest one dedicated to classrooms and laboratories and the smallest dedicated mainly to administrative functions. © Nelson Kon“We took the use of the lot to the maximum allowed by current legislation, adding two floors to the administrative block. In this way, it was possible to accommodate the project's extensive program, which ranges from kindergarten to high school. In this block, designed in a square plan, the central void was expanded, flooding all the floors with natural light”, says Artur Katchborian, architect and partner of Biselli Katchborian.  © Nelson KonIn addition to the existing indoor court, the project created two more uncovered courts, reactivating the access to the building's roof. The retrofit process in this case was highlighted due to new rules regarding safety and accessibility: the installation of elevators, the renovation of emergency stairs, and several other elements that needed to be adapted. © Nelson KonThe access to the school underwent major changes: the embarkation and disembarkation area was expanded and the main access gained institutional clarity, taking place through the administrative block at the level of the indoor patio. which extends from the facades to the internal environments unifies the blocks and establishes the educational institution's visual identity You'll now receive updates based on what you follow Personalize your stream and start following your favorite authors If you have done all of this and still can't find the email These little Phrygian caps were the mascots of Paris 2024 Inspired by the iconic Phrygian cap—a symbol of freedom—the Phryges were a vibrant tribe of red characters with a rich history The Phrygians have stood shoulder to shoulder with the French people throughout all the key moments in the nation’s history; today they are convinced that sport can change everything Our mascots aimed to play a role in the lives of French people encouraging everyone to bring more sport into daily life And who better to lead this sporting revolution for Paris 2024 than these spirited little Phrygian caps The Phryges are based on an item of clothing that is a symbol of freedom and has been a part of French history for centuries After featuring on certain flags in Latin America before becoming widely popularised by French revolutionaries the Phrygian cap has now become a familiar image in France the Phrygian cap can be seen on French national icon Marianne depicted in busts at town halls across the country and on stamps and is also covered in the national curriculum in schools as the Phrygian cap was present at major events in French history Records in the French National Archives show Phrygian caps worn during the construction of Paris’ Notre-Dame cathedral in 1163 Always thoughtful and an astute strategist she embarked on adventures only after carefully weighing all the pros and cons she knew the importance of evaluating every parameter to achieve her goals The Olympic Phryge led the movement of all who participated in sport Did you recognise the running prosthetic she proudly wears Her passion is to blaze a trail; some might say she is fearless but one thing is certain: she hates being bored and loves to try new things and regardless of whether she competes as part of a team or on her own With her mindset of being the perfect supporter celebrating athletes in all arenas and all the Games venues and partying to celebrate victories or get over defeats Did you recognize the running prosthetic she proudly wore Her passion was blazing trails; some might say she was fearless but one thing was certain: she hated boredom and loved trying new things whether competing as part of a team or on her own celebrating athletes in all arenas and at all Games venues and partying to celebrate victories or recover from defeats." the Phryges knew that any revolution required preparation Our two heroes spent the last two years working to get France and its people active Hosting the Games was a once-in-a-lifetime experience so no one wanted to miss out on the celebrations the Olympic Phryge and Paralympic Phryge shared one message: sport can change everything and our connection to nature—it was time to welcome more sport into our lives!" El domingo 18 de junio de 2023 falleció Daniel Mascote Reyes el dejo atras recuerdos invaluables y una impresión duradera en todas las personas con las que entró en contacto que era de ascendencia mexicana y nació el 4 de mayo de 1995 en Rome representó una hermosa fusión de culturas  Valerie Grace Reyes y Silvina Rose Reyes sus dos queridas hijas que fueron la alegría de su vida asumiendo amorosa y devotamente los deberes de la paternidad La compasión de Daniel se extendió a sus sobrinas y sobrinos lo que resultó en recuerdos perdurables de la pesca Atesoraba estos tiempos con su familia y buscaba constantemente  Daniel fue un oasis de consuelo y fortaleza para sus padres quienes ahora están de duelo por la pérdida de su apreciado hijo confiando el uno en el otro para recibir amor y consejos  Daniel era un alma amorosa y desinteresada reconocida por su inquebrantable dedicación a sus seres queridos el tenia un amor contagioso por el baile y una preocupación genuina por el bienestar de quienes lo rodean por lo que ninguna fiesta era completa sin su presencia Era muy atento y hacia que todos se sintieran incluidos y cuidados  convirtiéndolo en una presencia invaluable en la vida de su familia y amigos Gustavo Reyes y Michael Hernández son los portadores del féretro y soportarán el peso de la ausencia física de Daniel mientras recordándolo y el impacto que tuvo en sus vidas Los familiares y amigos están invitados a asistir a la visita domiciliaria de varios días que tendrá lugar del  del lunes 26 de junio de 2023 al jueves 29 de junio de 2023 Este tiempo permitirá que los seres queridos se reúnan ofrezcan apoyar y compartir sus recuerdos de Daniel  Se llevará a cabo una misa fúnebre el viernes 30 de junio a las 10:30 a lo que permitirá a todos los que conocieron a Daniel unirse al recuerdo y celebración de su vida Después del Entierro al cementerio Oaknoll Memorial Gardens para el Rosario Este tributo final permitirá que las personas se despidan por última vez y encuentren consuelo en los recuerdos que compartieron con Daniel  Daniel Mascote Reyes será recordado por su amor inquebrantable y devoción a su familia Su amor por la vida y energía contagiosa dejarán una huella imperecedera en el corazón de cualquiera que tuvo la suerte de conocerlo Que su espíritu descanse en la paz eterna y que su familia y amigos encuentran consuelo en los maravillosos recuerdos que guardan durante este momento difícil Home / Adrian Mascote By the time Adrian Mascote returned to NIU in 2014 he already had a healthy taste of the real world He and his wife Jessica built a life for themselves and their three daughters Adrian was working full-time at a warehouse in DeKalb he concluded his family was healthy and they were financially stable It was time to return to the campus he left in 2010 after the birth of his first child enrolling in 15 credit hours in the fall term “I’m focused and I’ll do anything to get this done.” When he felt overwhelmed he’d tell himself I’m not the first person to do this That reminder– plus a burning desire to get his family ahead — kept him going He and his fellow students in Professor Mahesh Subramony’s consulting class worked with Caterpillar to develop an executive on-boarding program Part of that program is being used by Caterpillar today Mascote is ready to on-board his own career and an emphasis on human resource management career opportunities are not likely to pass him by this time Area officers made several warrant arrests over the weekend 39-year-old Adam Gore of Streator was picked up in the 100 block of South Park Street in that city He was wanted for failing to appear to answer to a charge of violating an order of protection Gore is in the La Salle County jail in lieu of a thousand dollars to bond out 30-year-old Miguel Mascote of Streator was visited by police at home and taken in for failing to appear on a charge of driving while his license was revoked Your browser is out of date and potentially vulnerable to security risks.We recommend switching to one of the following browsers: IL — Joliet police say a 27-year-old resident was arrested early Sunday morning after he tried to run another motorist off the road on the city's east side near Joliet Central Officers later tracked down a pair of suspects and Jose Mascote was arrested on charges of aggravated assault driving while license suspended and resisting arrest was released on an I-Bond on charges of obstructing a peace officer That's when a patrol officer was flagged down by another motorist "The motorist was being followed by two males in a Chrysler Town and Country minivan," police spokesman Dwayne English announced "Officers learned that the minivan attempted to run the victim off of the roadway and was throwing items at the victim’s vehicle." Police saw the minivan near Cass and Scott but the driver chose not to stop and kept driving recklessly at excessive speeds The minivan headed on Joliet Street and then eastbound on Clinton Street and that's when the officers lost sight of the fleeing vehicle Joliet police found the vehicle in a grassy area near Joliet Central High School The driver and passenger of the minivan tried running away Officers identified the driver as Mascote and the passenger as Barbosa Get more local news delivered straight to your inbox. Sign up for free Patch newsletters and alerts. Andre Lima earned himself a tasty $25K before leaving the UFC Apex and headed straight to a tattoo parlor to get the teeth marks permanently imprinted onto his arm earning himself another $25K from the boss The UFC Vegas 89 prelim fight between Andre Lima and Igor Severino ended unceremoniously in the second round when Severino was disqualified after seeming to bite Lima in the clinch It wasn’t until the post-fight interview that viewers saw the extent of the bite with an almost perfect circle of teeth marks being shown on Lima’s arm – albeit still raised in victory Lima had an impressive showing and now moves to 8-0 as a professional with five wins coming by way of KO In the immediate aftermath of the disqualification win, Lima revealed that Dana White had awarded him an additional $25,000 in bonus money due to the manner in which the fight ended Yet that’s not where the story of the already-infamous ‘bite bonus’ ended – with Lima leaving the UFC Apex and heading towards a tattoo parlor to get the marks permanently inked on his skin Posting footage of the tattoo on social media Lima hilariously had the bite mark emblazoned with the words If Lima thought that the tattoo might have gained him a few more fans, he certainly couldn’t have imagined it earning him another post-fight bonus with Dana White sharing: “I was going to give him 25K “It was so insane I had to make it permanent! A debut to remember! Thanks boss @danawhite ! Ready for many more!” commented Lima. View this post on Instagram A post shared by Mascote (@andremascote__) Igor Severino was reportedly cut from the organization even before the UFC 89 Vegas broadcast had concluded This, according to a text conversation with Kevin Iole shared online by the veteran reporter, in which Dana White said that the issue has also been raised with the Nevada State Athletic Commission: “Those were two up-and-coming undefeated fighters. If you get frustrated and want out of the fight, there are plenty of ways to do it, but the worst thing u can do is bite your opponent. Now, you get cut and lose the biggest opportunity of your life.” “Not to mention, he’s going to have real problems with the NSAC,” said White. natural pet food via a subscription service Courtesy of Mascote FitBrazil, the biggest pet food market in Latin America and third worldwide is leading the region in some global pet food trends Brazilian producer Mascote Fit is a newer company participating in the local natural dog food segment The company is appealing to consumers differently from its competitors providing a fresher and more human experience to dogs Mascote Fit believes natural food is superior to any other type of dog nutrition nearly 50% of dogs suffer cancer during their lives can prevent up to 40% of cancer cases in dogs said “real food” (as he calls natural dog food) is a key element for better health and longevity He added that the company created its menus with the support of veterinarians and nutritionists to fulfill 100% of the nutritional requirements of pets Watanabe explained that the experience offered by Mascote Fit is different from other companies as it follows a subscription-based service to help monitor the results for pets over time the company uses only natural ingredients that cook gently with steam to ensure the nutrients are well-preserved Delivery is as often as the consumer requests: weekly Watanabe's perception of the Brazilian pet food market overall is positive as the pandemic boosted stray dog adoptions and the dog population in general his company grew 300% in the pandemic period Watanabe added that Mascote Fit’s food is tailor-made as recipes are optimal for each life phase (senior dogs while the packaging contains the precise quantity of calories that the dog (or cat) requires every day The company even prints a picture of each dog or cat on the package to engage with customers Brazilians are the biggest dog lovers in the region “Local consumers buy strollers for dogs and birthday cakes,” he said “We have daycares and other services for dogs that point toward an increasing humanization of pets in Brazil.” Relative to the market size of the nascent dog food segment Mascote Fit currently produces four tons a month there are bigger competitors in the market; the major local natural dog food player produces more than 40 tons per month foreshadowing a further increase in the natural dog food market in years to come By submitting this form, you acknowledge that use of your data is governed by our Privacy Policy. you agree to receive texts or calls regarding your subscription or other WATT products and services Please call +1 (847) 400-5960 for custom support | The victims who died in the crash have been identified by KHP as Armando David Mascote was transported to an area hospital with suspected serious injuries ORIGINAL STORY | The Kansas Highway Patrol said five people were killed in a two-vehicle crash on Interstate 70 near Maple Hill Sunday morning a Ford F-150 pickup truck was eastbound in the westbound lanes A person in the truck and four people in the van were killed At least one person suffered critical injuries I-70 WB was re-routed to Highway 24 for several hours Report a typo 2015 at 3:34 pm CT.css-79elbk{position:relative;}A Joliet man was charged with sexually abusing a 16-year-old girl David Mascote was arrested Wednesday and taken to the Will County jail “deputies were informed of a possible sexual assault on a 16 year old female victim,” the sheriff’s department said in a press release the assault had occurred in” Mascote’s car following a “family party.” Detectives secured a warrant for Mascote’s arrest the same day he was taken into custody Go take a look at our Facebook page. And make sure you read these fantastic stories as well: Andre Lima earned a $50,000 bonus for winning his UFC fight Saturday night Lima celebrated the unusual win by flexing the arm with the bite mark then later going to a local tattoo studio and permanently memorializing the rare victory bonus Bonuses are awarded at nearly every UFC event for categories such as Fight of the Night and Performance of the Night — given to the evening’s flashiest knockouts or submissions — but Bite of the Night appears to be an all-time first Tonight's BOTN 💰💰 #UFCVegas89 pic.twitter.com/Ngttbbryr8 — UFC (@ufc) March 24, 2024 was not only disqualified but later released from the promotion for his antic The 20-year-old Brazilian sunk his teeth in Lima around the 3-minute mark of the second round After Lima jerked back and showed referee Chris Tognoni his arm a Nevada State Athletic Commission doctor was brought into the octagon to examine Lima’s arm UFC President Dana White told MMA reporter Kevin Iole in a text message that he was cutting Severino “Those were two up-and-coming undefeated fighters,” White told Iole “If you get frustrated and want out of the fight but the worst thing u can do is bite your opponent you get cut and lose the biggest opportunity of your life he’s going to have real problems with the NSAC.” White initially gave Lima a $25,000 bonus for the unusual victory then doubled the bonus to $50,000 when the fighter went out to get the tattoo A post shared by Mascote (@andremascote__) Lima had the words “I got f—— bit bonus” inked around the teeth marks (Photo: Chris Unger / Zuffa LLC via Getty Images) There was no quit in the Joliet Central girls soccer team Coming off four straight losses and going on the road in their most recent game But Juli Calderon scored her first high school hat trick and they came roaring back with five straight goals to defeat Shepard 5-1 on Monday evening The win not only matched the Steelmen (2-4) victory total from last season (2-13-1) it showed their resolve "We had to just give it our best and not put our heads down," Calderon said they were and the five goals were the most by a Joliet Central team since a 10-0 win over Rich Township on March 25 "It really was a group effort," Joliet Central coach Stephanie Phillips said "We played a better second half and kept the same mindset no matter what the score is." which lost to the Steelmen 2-1 last year on March 17 in the Windy City Ram Classic Tournament March 20 by the score of 2-1 against Oak Forest So when Megan Kempczynski took a nice run and scored into the right corner off an assist from fellow senior Ximena Delgado with 23:47 left in the first half "It was a give-and-go," Kempczynski said of her second tally of the season "It was great and we felt really good But then our communication just wasn't there We fell apart in the middle and they were able to get some goals." 1-0 on March 14 against Oak Forest at Glenbard East as part of the Windy City Ram Classic when sophomore Victoria Davila scored with 17:36 left to play in the game made sure they got on the board as she scored off an assist from senior Liz Gutierrez in front with 13:25 left in the first half Joliet Central senior midfielder Sara Mascote had some good opportunities but couldn't connect took charge for the last 20 minutes of the game Calderon chipped a shot from the right side It went off the keeper's hands and settled just inside the left post for a 2-1 advantage with 19:53 to play Calderon then completed her first high school hat trick as she blasted in a restart from 28 yards out with 16:51 remaining.  "It felt great," Calderon said of getting her first high school hat trick "We just told each other to push more and not keep our heads down." who has just committed to continuing her career at the University of St who recently committed to Joliet Junior College and Jacqueline Morales helped make sure of that.  So did senior goalkeeper Madison Schlismann who Phillips said "kept us in the game" with some nice saves Junior Gisselle Rangel also played well on defense and junior Emma Schlismann alternated between defense and center midfielder That paid dividends when Emma Schlismann scored on a nice run with 8:12 to play. Davila dented the back of the net as she took an assist from Calderon and scored with 2:24 left to round out the scoring The Astros had a penalty kick opportunity with 1:10 remaining that went wide left "Juli has been solid and has been on varsity since she was a freshman," Phillips said of Calderon "She's someone to be on the lookout for." who played soccer at Lemont and has been a coach at Joliet Central for the past nine years is looking forward to some of the Steelmen's upcoming games in the Southwest Prairie Conference They were off for the rest of this week but host Minooka on Thursday and travel crosstown to play Joliet West on Thursday and Joliet West next and we are looking to compete with them," said Phillips "The girls really stepped up (against Shepard) This team is very united and all get along with each other © 2024 Joliet Township High School Igor Severino's life isn't the same as it was one week ago As of now, the 20-year-old ex-UFC fighter doesn't know if it'll ever be even similar after he bit opponent Andre Lima during their March 23 fight at UFC on ESPN 53 in Las Vegas The highly unusual and flagrant foul disqualified him from the bout and made international headlines far beyond the combat sports bubble "It's been crazy – some crazy days," Severino told MMA Junkie as he spoke on the incident for the first time publicly since it happened I was fighting in the best promotion in the world Severino's face appeared all over social media as the video went viral His accounts were flooded with comments and messages Severino remained out of the public eye and ear over the past six days until now as he processed why and how he did what he did Severino said he still hasn't figured it all out "I come from humble beginnings," Severino said I left my home as a teenager to come over to train and to get here to see all of this go away and in the way it did It makes me very emotional and sad about it to Mick (Maynard) – everyone in the organization – and the fans Sorry to everyone who was watching that on TV Severino said he reached into his memory bank but came up empty-handed as to why he chomped his opponent's left tricep during a takedown attempt along the fence He said he has no recollection of the sequence or its surroundings and was shocked when he watched the tape back Severino mentioned that a strike earlier in the fight may have caused insensible behavior "I remember everything that was happening until I got hit with something really hard," Severino said "I watched the video later and I thought it was an elbow the action is not reflective of his character He added there have not been prior issues in the way he's carried himself in any of his past fights "You can talk with anyone that we've fought with or anyone who has promoted one of my fights," Severino said "I've always fought with respect and laid it down in the cage I've never done anything outside the barriers of the sport It's been Severino's dream for years to fight in the UFC He said fighting is how he provides for his family So why bite an opponent given the circumstances Severino struggled to calculate the math in hindsight or you could say I was winning," Severino said "There was nothing that could justify me biting." The bite caused punishments from multiple directions. Severino was disqualified in the bout by referee Chris Tognoni as Lima sported a deep bite mark (which he tattooed on himself hours later) UFC CEO Dana White announced Severino was cut the Nevada Athletic Commission (NAC) has since withheld his purse Severino said he understands and accepts that punishment should come from the incident but also doesn't agree with the notion his MMA career – or prospects of a second UFC shot down the line – should be killed He also finds the commission's purse withholding somewhat severe I think that's one of the worst things that could've happened so I'm not even sure if I'll get paid anything I'm not sure what they're even going to decide because this money isn't even for me It's for my whole family that depends on me It's how I'm able to take care of my sick family members It's all that I have to make a means to live." Severino revealed another layer of response that irked him deeper than the rest – one that was difficult for him to speak about without emotion flowing out received threatening messages after the incident Severino broke down crying when he spoke about his inability to truthfully give his mother proper reassurance "They have been going after my loved ones," Severino said My mother doesn't have anything to do with it My family doesn't have anything to do with it What I did was wrong but it was far from a crime They're treating me like I'm the worst person in the world crying about people threatening her and saying all kinds of stuff to her and about her I had to try to calm her down and tell her everything is going to be OK I don't know if everything is going to be OK I don't even know if I have a career after this." While the majority of messages and comments were negative various fighters and teammates defended Severino's character on social media Lima spoke out in Severino's defense during multiple interviews following the incident and advocated for his disqualified opponent to get a second UFC opportunity Lima even went as far as to say he'd give Severino a rematch "He had every right to condemn me and to surf the wave of this moment he's extending his hand to me," Severino said He's saying he would even offer me a rematch I can't express how much admiration I've gained from him Someone who was so honorable and so graceful toward me I just wish him the best things in the world If he ever needs a sparring partner for one of his fights he can call me any time and I'll be available even if it doesn't end up changing anything with my situation with the UFC and this sport it already means more than any other thing He could be trampling on me and he's doing the opposite People who should be with me are trying to bash me That shows the nature of the person that he is I wish he has the best of luck in his life because he seems to be a great person." While it might take time for the public perception to reconstruct Severino hopes the UFC and other promotions don't view him with a closed mind going forward Severino doesn't want an isolated mistake to be his entire story and is determined to do whatever it takes to prove he deserves a road to redemption but I wish I had a chance to redeem myself," Severino said "I don't want to be defined as a 20-year-old kid who bit a guy in the cage and was banned from the sport Everyone that knows me knows that's not the kind of person that I am I really don't want to be defined as the kid who bit his opponent and ruined his life I know things look pretty bad for me right now and I just want people to see the person that I am to see that's not who I am as a fighter or as a person Please give me a chance to come back and redeem myself Please let me show you all who I really am." MMA Junkie reached out to the NAC for comment on the purse withholding, but the commissioning body declined to comment. The NAC has temporarily withheld purses or partial purses in the past, including $2 million from Khabib Nurmagomedov for jumping on Conor McGregor in 2018. Nurmagomedov was eventually paid back $1.5 million of that It's expected a potential fine and/or suspension for Severino will be discussed at a NAC meeting in the coming months Lima was awarded a $50,000 "Bite of the Night" bonus from White as a result of the unusual circumstances and follow-up tattoo This story was updated April 2 at 3:20 p.m ET to reflect the NSAC's declination for comment on the matter Metrics details Copy-number aberrations (CNAs) and whole-genome duplications (WGDs) are frequent somatic mutations in cancer but their quantification from DNA sequencing of bulk tumor samples is challenging Standard methods for CNA inference analyze tumor samples individually; however DNA sequencing of multiple samples from a cancer patient has recently become more common We introduce HATCHet (Holistic Allele-specific Tumor Copy-number Heterogeneity) an algorithm that infers allele- and clone-specific CNAs and WGDs jointly across multiple tumor samples from the same patient We show that HATCHet outperforms current state-of-the-art methods on multi-sample DNA sequencing data that we simulate using MASCoTE (Multiple Allele-specific Simulation of Copy-number Tumor Evolution) Applying HATCHet to 84 tumor samples from 14 prostate and pancreas cancer patients we identify subclonal CNAs and WGDs that are more plausible than previously published analyses and more consistent with somatic single-nucleotide variants (SNVs) and small indels in the same samples These methods rely on various simplifying assumptions such as: only one tumor clone is present in the sample While these assumptions remove ambiguity in copy-number deconvolution it is not clear that the resulting solutions are accurate particularly in cases of highly aneuploid tumors available methods for inferring CNAs analyze individual samples losing the important information that multiple samples from the same patient share many CNAs that occurred during tumor evolution HATCHet separates two distinct sources of ambiguity in the copy-number deconvolution problem the presence of subclonal CNAs and the occurrence of WGDs and uses a model-selection criterion to distinguish these sources existing methods attempt to fit a unique value for the variables tumor ploidy and purity (or equivalent variables) to the observed RDRs and BAFs conflating different sources of ambiguity in the data We show that HATCHet’s inferred subclonal CNAs and WGDs are more plausible than reported in published analyses and more consistent with somatic SNVs and small indels measured in the same samples resulting in alternative reconstructions of tumor evolution and metastatic seeding patterns a HATCHet takes in input DNA sequencing data from multiple bulk tumor samples of the same patient and has five steps HATCHet calculates the RDRs and BAFs in bins of the reference genome (black squares) HATCHet clusters the bins based on RDRs and BAFs globally along the entire genome and jointly across samples p and q Each cluster (color) includes bins with the same copy-number state within each clone present in p or q HATCHet estimates two values for the fractional copy number of each cluster by scaling RDRs the identification of the cluster (magenta) with copy-number state (1, 1) is sufficient and RDRs are scaled correspondingly HATCHet identifies an additional cluster with identical copy-number state in all tumor clones Dashed black horizontal lines in the scaled BAF-RDR plot represent values of fractional copy numbers that correspond to clonal CNAs HATCHet factors the allele-specific fractional copy numbers FA, FB into the allele-specific copy numbers A, B there is a normal clone and 3 tumor clones HATCHet’s model-selection criterion identifies the matrices A and U in the factorization while evaluating the fit according to both the inferred number of clones and presence/absence of a WGD g HATCHet outputs allele- and clone-specific copy numbers (with the color of the corresponding clone) and clone proportions (in the top right part of each plot) for each sample Clusters are classified according to the inference of unique/different copy-number states in each sample (sample-clonal/subclonal) and across all tumor clones (tumor-clonal/subclonal) tumor ploidy and purity are composite variables that sum the contributions of the unknown copy numbers and proportions of multiple clones tumor ploidy and purity are not ideal coordinates to evaluate tumor mixtures as many different clonal compositions may be equally plausible in these coordinates particularly when more than one tumor clone is present or a WGD occurs (Supplementary Figs a simulation framework to correctly generate DNA sequencing reads from multiple bulk tumor samples with each sample containing one or more clones that share the same evolutionary history during which CNAs and/or WGD occur (Supplementary Fig We simulated DNA sequencing reads from 256 tumor samples (1–3 tumor clones) for 64 patients (3–5 samples per patient) half with a WGD and half without a WGD (Supplementary Fig We separated the comparison of methods into two parts in order to assess both the inference of CNAs and proportions we provided the true values of the main parameters inferred by each method to assess the ability to retrieve the correct solution without the difficulty of model selection we applied HATCHet jointly on all samples as well as separately on each sample (single-sample HATCHet) to quantify the contribution of the global clustering and the factorization model which capture the dependency across samples Further details are in Supplementary Notes 1 and 2 a Average allele-specific error per genome position for the copy-number states and their proportions inferred by each method (here excluding THetA which does not infer allele-specific copy numbers) on 128 simulated tumor samples from 32 patients without a WGD and where each method was provided with the true values of the main parameters (e.g. HATCHet outperforms all the other methods even when it considers single samples individually (single-sample HATCHet) b Average allele-specific error per genome position on 256 simulated tumor samples from 64 patients and where each method infers all relevant parameters including tumor ploidy even when considering single samples individually (single-sample HATCHet) Box plots show the median and the interquartile range (IQR) and the whiskers denote the lowest and highest values within 1.5 times the IQR from the first and third quartiles c Average precision and recall in the prediction of the absence of a WGD and the presence of a WGD in a sample HATCHet is the only method with high precision and recall (>75%) in both the cases even compared to a consensus of the other methods based on a prediction for majority While Battenberg and Canopy underestimate the presence of WGDs (<20% and 0% recall) and cloneHD overestimates the absence of WGDs (<20% we observed a reasonable consistency between HATCHet’s profiles and those from single cells (Supplementary Figs Additional details of this analysis are reported in Supplementary Note 5 An important question is whether this difference is due to cancer-type specific or patient-specific differences in CNA evolution of these tumors or a consequence of differences in the bioinformatic analyses We investigated whether the HATCHet’s analysis would confirm or refute the discordance between these studies a HATCHet identifies subclonal CNAs in 29 samples while Battenberg identifies subclonal CNAs in all 49 samples b In the 29 samples where both methods identify subclonal CNAs HATCHet and Battenberg infer similar fractions of the genome with subclonal CNAs (dotted diagonal) while in the other 20 samples only Battenberg retrieves relatively high fractions of subclonal CNAs both HATCHet and Battenberg identify reliable subclonal CNAs that correspond to sample-subclonal clusters (magenta) with clearly intermediate positions in the scaled BAF-RDR plot (each point corresponds to 50 kb genomic bin) between those of sample-clonal clusters (black clusters with corresponding copy-number states) with clonal CNAs (dashed black lines) d The sample-subclonal clusters in c correspond to large genomic regions (magenta) with values of RDR (for 50kb genomic bins) clearly distinct from the RDR values of regions from sample-clonal clusters (black) Battenberg identifies extensive clusters of 50kb genomic bins with subclonal CNAs (green) such clusters are not clearly distinguished in the scaled BAF-RDR plot from the sample-clonal clusters (black with corresponding copy-number states) HATCHet infers only clonal CNAs in this sample f The sample-subclonal clusters in e correspond to large genomic regions (green) with values of RDR (for 50kb genomic bins) approximately equal to the RDR values of nearby regions from sample-clonal clusters (black) While it is possible that Battenberg has higher sensitivity in detecting subclonal CNAs than HATCHet the extensive subclonal CNAs reported by Battenberg in all samples is concerning This is because the inference of subclonal CNAs will always produce a better fit to the observed RDRs and BAFs but with a cost of increasing the number of parameters required to describe the copy-number states (model complexity) Battenberg models the clonal composition of each segment independently (Supplementary Fig and thus has 6× more parameters than HATCHet on this dataset (Supplementary Fig it is important to evaluate the trade-off between model fit and model complexity Battenberg does not include a model-selection criterion to evaluate this trade-off and it consequently infers a high fraction of subclonal CNAs in every sample (Supplementary Note 7) without fitting the observed RDRs and BAFs better than HATCHet (Supplementary Note 8) HATCHet uses a model-selection criterion to identify the number of clones; consequently in 20/49 samples HATCHet infers that all the subclonal CNAs identified by Battenberg are instead clonal (Supplementary Fig Since HATCHet fits the observed RDRs and BAFs as well as Battenberg (Supplementary Fig the extensive subclonal CNAs reported by Battenberg in these samples are equally well-explained as clonal CNAs we found that ReMixT’s inference of subclonal CNAs from the same dataset was more similar to HATCHet than Battenberg (Supplementary Fig Since both HATCHet and ReMixT outperformed Battenberg on the simulated data the similarity between HATCHet and ReMixT on this dataset suggests that Battenberg’s results are less accurate Further details of this analysis are in Supplementary Note 9 a HATCHet identifies subclonal CNAs in 15 of 35 samples while published analysis used Control-FREEC and excluded subclonal CNAs b In the lymph node metastasis sample Pam01_NoM1 HATCHet infers two distinct tumor clones (ellipses in lower right of plot with corresponding proportions) and a tumor purity of 69% Five sample-subclonal clusters (arrows) of 50kb genomic bins occupy intermediate positions between the other sample-clonal clusters (dashed black lines) in the scaled BAF-RDR plot and thus have distinct copy-number states in the two clones Control-FREEC copy numbers are shown on the right y-axis labels c In a second liver metastasis sample Pam01_LiM2 from the same patient one (red) shared with the lymph node sample Pam01_NoM1 starred) occupies an intermediate position in the scaled BAF-RDR plot and has distinct copy-number states in the two clones the five sample-subclonal clusters in Pam01_NoM1 (arrows) clearly overlap the sample-clonal clusters in this sample and thus correspond to clonal CNAs (dashed black lines) d In the liver metastasis sample Pam01_LiM1 HATCHet identifies a single tumor clone (white) that is shared with the lymph node metastasis sample Pam01_NoM1 in b The five sample-subclonal clusters in Pam01_NoM1 (arrows) correspond to clonal CNAs in sample Pam01_LiM1 but have different copy-number states than those in c The inferred low tumor purity (28%) of this sample results in a partial overlap of clusters that are clearly distinguished in higher purity samples in b and c e The five sample-subclonal clusters in Pam01_NoM1 (arrows) correspond to large genomic regions with values of RDR that are clearly distinct from the other sample-clonal clusters (dashed black lines) Genomic regions that are part of small clusters or have out-of-scale values are reported in gray Ranges of fractional copy numbers corresponding to the total copy numbers inferred by Control-FREEC in the previously published analysis are shown on the right y-axis labels additional analyses of RDRs and BAFs further support the subclonal CNAs identified by HATCHet (Supplementary Note 12 and Supplementary Figs We investigated whether HATCHet analysis would confirm or refute the different prevalence of WGDs reported in the previous studies a HATCHet predicts a WGD in all 31 samples from three patients (Pam02 published analysis used Control-FREEC and excluded WGDs HATCHet predicts a WGD and infers two tumor clones (ellipses in upper right of plot with corresponding proportions) with seven large tumor-clonal clusters (arrows with corresponding copy-number states) These clusters preserve their relative positions in the scaled BAF-RDR plot (each point corresponds to 50kb genomic bin) across samples and their fractional copy numbers correspond to sample-clonal clusters in each sample (dashed black lines) supporting the inference of a tumor-clonal CNA (i.e, unique copy-number state across samples) for each of these clusters Note that without a WGD three clusters (red dashed squares) would correspond to subclonal CNAs in all samples starred) are tumor-subclonal as they change their relative position across samples (Pam02_PT18 and Pam02_LiM4 vs supporting the inference of two distinct tumor clones in this patient The total copy numbers inferred by Control-FREEC in published analysis are shown on the right y-axis labels in the first scaled BAF-RDR plot a A genomic segment (cyan rectangle) harbors a somatic mutation which corresponds to either a somatic SNV or small indel Reads with variant allele (red squares) and reference allele (gray squares) are used to estimate the VAF (Top right) From T sequencing reads (gray rectangles) covering the mutation red area of posterior probability) on the VAF is obtained from a binomial model copy-number states and proportions are inferred for this genomic segment Given the numbers \({\tilde{c}}_{1},{\tilde{c}}_{2}\) of mutated copies in each of the two copy-number states the \(\overline{{\rm{VAF}}}\) of the mutation is computed as the fraction of the mutated copies weighted by the proportions of the corresponding copy-number states Assuming that an allele-specific position is mutated at most once during tumor progression (i.e. all possible values of \(\overline{{\rm{VAF}}}\) are computed according to the possible values of \({\tilde{c}}_{1}\) and \({\tilde{c}}_{2}\) A mutation is explained if at least one value of \(\overline{{\rm{VAF}}}\) is within CI b Over 10,600 mutations identified per prostate cancer patient on average HATCHet copy numbers (red) yield fewer unexplained mutations than Battenberg (blue) in all patients but A29 c Over 9,000 mutations identified per pancreas cancer patient on average HATCHet copy numbers yield fewer unexplained mutations in all patients than Control-FREEC we observed that nearly all mutations have low VAFs (Supplementary Fig consistent with low tumor purity as well as the presence of WGDs and/or higher ploidy in these samples SNVs/indels that occur after WGDs alter only one copy of the locus As lower VAFs are also observed in samples with higher purity (e.g. WGDs and high ploidy are the more likely explanation for the low VAFs consistent with HATCHet’s prediction of WGD in 3/4 patients (Supplementary Fig a CCFs of somatic SNVs and small indels in samples A10-C and A10-E of patient A10 computed from allele-specific copy numbers and proportions inferred by HATCHet (top) and Battenberg (bottom) HATCHet explains a substantial number of mutations that are unexplained by Battenberg; for example HATCHet infers a clonal CNA on chromosome 1p in A10-E and determines that the mutations at this locus (purple circle) are clonal (i.e. Battenberg infers subclonal CNAs at the same locus and determines that the same mutations are subclonal (CCF ≈ 0.3) b CCFs of somatic SNVs and small indels in samples A17-A and A17-F of patient A17 show groups of mutations that are explained by HATCHet and unexplained by Battenberg (only this subset of mutations is shown here for simplicity) HATCHet infers a clonal CNA on chromosome 8q in A17-F and suggests that mutations in that region (green circle) are clonal (CCF ≈ 1) while Battenberg infers subclonal CNAs and suggests that the same mutations are subclonal (CCF ≈ 0.5) c CCFs of somatic SNVs and small indels in samples A22-J and A22-H of patient A22 show a large group of shared mutations on chromosome 8p (cyan circle with CCF > 0 in both samples) HATCHet infers the same copy-number state (2, 0) in both samples Battenberg infers distinct copy-number states (1, 0) and (2, 0) in the two samples and suggests that the mutations are subclonal in both samples since the unexplained mutations are classified as subclonal in both samples based on Battenberg’s results these mutations are classified as clonal and are not evidence of polyclonal migration and in some cases assuming that copy numbers are the same in all tumor cells in a sample we showed the advantage of separating the two sources of ambiguity in copy-number deconvolution: ambiguity in fractional copy numbers vs ambiguity in the factorization of fractional copy numbers into integer-valued copy-number states HATCHet defers the selection of fractional copy numbers performing model selection in the natural coordinates of copy-number states and clone proportions a simulator for multi-sample tumor sequencing data that correctly accounts for different genome lengths of tumor clones and WGD we showed that HATCHet outperforms existing methods for CNA inference on simulated bulk tumor samples and produces more plausible inferences of subclonal CNAs and WGDs on two cancer datasets The increasing availability of DNA sequencing data from multiple bulk tumor samples from the same patient provides the substrate for deeper analyses of tumor evolution over time Algorithms that maximally leverage this data to quantify the genomic aberrations and their differences across samples will be essential in translating this data into actionable insights for cancer patients an algorithm to infer allele- and clone-specific CNAs and clone proportions for several tumor clones jointly across multiple bulk tumor samples We represent the accumulation of all CNAs in all clones by partitioning the L genomic positions of the reference genome into m segments with each segment s consisting of ℓs genomic positions with the same copy numbers in every clone a clone i is represented by a pair of integer vectors ai and bi whose entries indicate the number of copies of each of the two alleles for each segment we define the copy-number state (as,i, bs,i) of segment s in clone i as the pair of the two integer allele-specific copy numbers as,i and bs,i whose sum determines the total copy-number cs,i = as,i + bs,i we define clone 1 to be the normal (non-cancerous) diploid clone and thus (as,1, bs,1) = (1, 1) and cs,1 = 2 for every segment s of the normal clone We represent the allele-specific copy numbers of all clones as two m × n matrices A = [as,i] and B = [bs,i] we represent the total copy numbers of all clones as the m × n matrix C = [cs,i] = A + B the genome length \({L}_{i}=\mathop{\sum }\nolimits_{s = 1}^{m}{c}_{s,i}{\ell }_{s}\) of every tumor clone i is generally different from the genome length L1 = 2L of the normal clone We obtain DNA sequencing data from k samples of a cancer patient and we assume that each tumor sample p is a mixture of at most n clones with clone proportion ui,p indicating the fraction of cells in p that belong to clone i Note that 0 ≤ ui,p ≤ 1 and the sum of clone proportions is equal to 1 in every sample p We say that i is present in p if ui,p > 0 The tumor purity \({\mu }_{p}=\mathop{\sum }\nolimits_{i = 2}^{n}{u}_{i,p}\) of sample p is the sum of the proportions of all tumor clones present in p We represent the clone proportions as the n × k matrix U = [ui,p] We describe the details of these two modules in the next two sections The first module of HATCHet aims to infer the allele-specific fractional copy numbers FA and FB from the DNA sequencing data of k samples Further details are in Supplementary Methods 1 and 2 We introduce an approach to estimate FA and FB with rigorous and clearly-stated assumptions we assume there is a reasonable number of genomic positions in segments whose total copy number is 2 in all clones; this is generally true if a reasonable proportion of the genome is not affected by CNAs and hence diploid we assume there are two groups of segments whose total copy numbers are distinct and the same in all clones; this is also reasonable if some segments are affected only by WGD and tumor clones accumulate clonal CNAs during tumor evolution we scale the RDR rs,p of each segment s in every sample p into the fractional copy number fs,p and separate fs,p into the allele-specific fractional copy numbers \({f}_{s,p}^{A},{f}_{s,p}^{B}\) using the BAF βs,p The following theorem states that the assumptions above are sufficient for scaling RDRs to fractional copy numbers Theorem 1: The fractional copy number fs,p of each segment s in each sample p can be derived uniquely from the RDR rs,p and either (1) a diploid clonal segment \({s}^{\prime}\) with total copy number \({c}_{{s}^{\prime},i}=2\) in every clone i or (2) two clonal segments \({s}^{\prime}\) and \({z}^{\prime}\) with total copy numbers \({c}_{{s}^{\prime},i}={\omega }_{{s}^{\prime}}\) and \({c}_{{z}^{\prime},i}={\omega }_{{z}^{\prime}}\) for all tumor clones i and such that \({r}_{{s}^{\prime},p}({\omega }_{{z}^{\prime}}-2)\ne {r}_{{z}^{\prime},p}({\omega }_{{s}^{\prime}}-2)\) for all samples p this theorem states that the scaling is independent of other copy numbers in A and C as well as the clone proportions in U The second module of HATCHet aims to derive allele- and clone-specific copy numbers A, B and clone proportions U from the two values of allele-specific fractional copy numbers FA and FB that were estimated in the first module The first step of the second module is the inference of A, B, and U from each estimated value of FA and FB (Fig. 1e) Since the samples from the same patient are related by the same evolutionary process we model the fractional copy numbers jointly across the k samples such that FA = AU and FB = BU the problem that we face is to simultaneously factorize FA and FB into the corresponding allele-specific copy numbers A B and clone proportions U for some number n of clones Problem 1: (Allele-specific Copy-number Factorization (ACF) problem) Given the allele-specific fractional copy numbers FA and FB and the number n of clones find allele-specific copy numbers A = [as,i] B = [bs,i] and clone proportions U = [ui,p] such that FA = AU and FB = BU While the ACF problem is a mathematically elegant description of the copy-number deconvolution problem there are two main practical issues: first measurement errors in FA and FB may result in the ACF problem having no solution and second the ACF problem is an underdetermined problem and multiple factorizations of a given FA and FB may exist we do not solve the simultaneous factorization FA = AU and FB = BU exactly but rather minimize the distance between the estimated fractional copy numbers FA and FB and the factorizations AU and BU weighted by the corresponding size of the clusters we define the distance \(\parallel {F}^{A}-AU\parallel =\mathop{\sum }\nolimits_{s = 1}^{m}\mathop{\sum }\nolimits_{p = 1}^{k}{\ell }_{s}| {f}_{s,p}^{A}-{\sum }_{1\le i\le n}{a}_{s,i}{u}_{i,p}|\) where ℓs is the genomic length of the cluster s We also define the corresponding distance for FB Problem 2: (Distance-based Constrained Allele-specific Copy-number Factorization (D-CACF) problem) Given the allele-specific fractional copy numbers FA and FB a maximum total copy number \({c}_{\max }\) a minimum clone proportion \({u}_{\min }\) B = [bs,i] and clone proportions U = [ui,p] such that: the distance D = ∥FA − AU∥ + ∥FB − BU∥ is minimum; \({a}_{s,i}+{b}_{s,i}\le {c}_{\max }\) for every cluster s and clone i; either \({u}_{i,p}\ge {u}_{\min }\) or ui,p = 0 for every clone i and sample p; for every cluster s either as,i ≥ θ or as,i ≤ θ for all clones i; for every cluster s either bs,i ≥ θ or bs,i ≤ θ for all clones i We also derive an ILP formulation that gives exact solutions for small instances HATCHet uses one of these two algorithms to infer A, B, U from FA, FB Further details of this problem and methods are in Supplementary Method 4 perhaps increasing the sensitivity to detect small subclonal CNAs but with a danger of overfitting the data and overestimating n and the presence of subclonal CNAs; ignore the trade-off between subclonal CNAs (related to a higher number of clones) and WGD (related to a higher value of tumor ploidy) by not evaluating the presence or absence of WGD in the model selection Following the factorizations of the two values of FA and FB (corresponding to the cases of WGD and no WGD) HATCHet chooses the simplest solution that minimizes the total number n of clones across all samples Further details on the model-selection procedure are in Supplementary Method 5 HATCHet introduces an explicit model-selection criterion to select among different allele- and clone-specific copy numbers and clone proportions that explain the observed DNA sequencing data There are often multiple possible mixtures of allele-specific copy numbers that explain the measured RDRs and BAFs: for example segments with distinct values of RDR and BAF could be explained as either subclonal CNAs or clonal CNAs with high copy numbers It is difficult to distinguish these cases because the total length of the genome of each tumor clone is unknown HATCHet introduces a model-selection criterion which separates two distinct sources of this ambiguity: (1) the inference of allele-specific fractional copy numbers FA and FB which are not uniquely determined by the measured RDRs and BAFs; (2) the inference of the allele- and clone-specific copy numbers A, B and the clone proportions U HATCHet evaluates two possible values of FA, FB—corresponding to the occurrence of WGD or not—and defers the selection of a solution until after the copy-number deconvolution HATCHet performs model selection in the natural coordinates of the problem and evaluates the trade-off between inferring subclonal CNAs (and thus more clones present in a sample) or a WGD (Supplementary Fig when modeling a large number of distinct copy-number states Supplementary Table 2 lists the parameters used in HATCHet’s model-selection criterion and Supplementary Table 3 provides the default values of these parameters the expected proportion vs,i of reads in segment s that originate from clone i is equal to \({v}_{s,i}={\ell }_{s}\frac{{c}_{s,i}{u}_{i}}{\mathop{\sum }\limits_{j=1}^{n}{u}_{j}{L}_{j}}\) the fraction of the genome content from segment s belonging to the cells of clone i (Supplementary Method 1) 6c); (4) MASCoTE simulates each sample p by considering an arbitrary subset of the clones (always containing the normal clone) with random clone proportions and by mixing the corresponding reads using the read proportion \({v}_{i,p}=\frac{{u}_{i,p}{L}_{i}}{\sum _{1\le j\le n}{u}_{j,p}{L}_{j}}\) (Supplementary Fig Further details about this procedure are in Supplementary Method 6 We ran every method on the simulated samples by using the default available pipelines Details about the experimental setting of every method are described in Supplementary Note 1 Further information on research design is available in the Nature Research Reporting Summary linked to this article HATCHet is available on GitHub at https://github.com/raphael-group/hatchet. MASCoTE is available on GitHub at https://github.com/raphael-group/mascote The clonal evolution of tumor cell populations Emerging landscape of oncogenic signatures across human cancers The causes and consequences of genetic heterogeneity in cancer evolution Biological and therapeutic impact of intratumor heterogeneity in cancer evolution Pan-cancer patterns of somatic copy number alteration Absolute quantification of somatic DNA alterations in human cancer Dentro, S. C. et al. Characterizing genetic intra-tumor heterogeneity across 2,658 human cancer genomes. Preprint at https://doi.org/10.1101/312041 (2018) Genome doubling shapes the evolution and prognosis of advanced cancers Heterogeneity of genomic evolution and mutational profiles in multiple myeloma The evolutionary history of lethal metastatic prostate cancer Tracking the evolution of non–small-cell lung cancer Inferring parsimonious migration histories for metastatic cancers Allele-specific copy number analysis of tumors Allele-specific copy number profiling by next-generation DNA sequencing Sequenza: allele-specific copy number and mutation profiles from tumor sequencing data TITAN: inference of copy number architectures in clonal cell populations from tumor whole-genome sequence data FACETS: allele-specific copy number and clonal heterogeneity analysis tool for high-throughput DNA sequencing Copy-number analysis and inference of subclonal populations in cancer genomes using Sclust Control-FREEC: a tool for assessing copy number and allelic content using next-generation sequencing data THetA: inferring intra-tumor heterogeneity from high-throughput DNA sequencing data Quantifying tumor heterogeneity in whole-genome and whole-exome sequencing data in International Conference on Research in Computational Molecular Biology Phylogenetic copy-number factorization of multiple tumor samples High-definition reconstruction of clonal composition in cancer A renewed model of pancreatic cancer evolution based on genomic rearrangement patterns ReMixT: clone-specific genomic structure estimation in cancer Single-cell genome sequencing: current state of the science Intratumor heterogeneity and branched evolution revealed by multiregion sequencing Limited heterogeneity of known driver gene mutations among the metastases of individual patients with pancreatic cancer Monitoring chronic lymphocytic leukemia progression by whole genome sequencing reveals heterogeneous clonal evolution patterns PyClone: statistical inference of clonal population structure in cancer SciClone: inferring clonal architecture and tracking the spatial and temporal patterns of tumor evolution Reconstruction of clonal trees and tumor composition from multi-sample sequencing data Inferring the mutational history of a tumor using multi-state perfect phylogeny mixtures PhyloWGS: reconstructing subclonal composition and evolution from whole-genome sequencing of tumors Assessing intratumor heterogeneity and tracking longitudinal and spatial clonal evolutionary history by next-generation sequencing Scalable whole-exome sequencing of cell-free DNA reveals high concordance with metastatic tumors tHapMix: simulating tumour samples through haplotype mixtures Combining tumor genome simulation with crowdsourcing to benchmark somatic single-nucleotide-variant detection A community effort to create standards for evaluating tumor subclonal reconstruction CLImAT: accurate detection of copy number alteration and loss of heterozygosity in impure and aneuploid tumor samples using whole-genome sequencing data Copy number aberrations from Affymetrix SNP 6.0 genotyping data—how accurate are commonly used prediction approaches Chemoresistance evolution in triple-negative breast cancer delineated by single-cell sequencing Multiclonal invasion in breast tumors identified by topographic single cell sequencing Pancreatic cancer metastases harbor evidence of polyclonality Integrated genomic characterization of pancreatic ductal adenocarcinoma Principles of reconstructing the subclonal architecture of cancers Kleinheinz, K. et al. ACEseq-allele specific copy number estimation from whole genome sequencing. Preprint at https://doi.org/10.1101/210807 (2017) Phylogenetic quantification of intra-tumour heterogeneity in International Workshop on Algorithms in Bioinformatics Complexity and algorithms for copy-number evolution problems Calder: Inferring phylogenetic trees from longitudinal tumor samples High-resolution mapping of copy-number alterations with massively parallel sequencing Copy number variation detection in whole-genome sequencing data using the bayesian information criterion Carter, S., Meyerson, M. & Getz, G. Accurate estimation of homologue-specific DNA concentration-ratios in cancer samples allows long-range haplotyping. Preprint at https://doi.org/10.1038/npre.2011.6494.1 (2011) Correcting for cancer genome size and tumour cell content enables better estimation of copy number alterations from next-generation sequence data ART: a next-generation sequencing read simulator dbSNP: the NCBI database of genetic variation association mapping and population genetical parameter estimation from sequencing data VarScan 2: somatic mutation and copy number alteration discovery in cancer by exome sequencing Download references and David Wedge for assistance in running Battenberg on our simulated data We thank Gavin Ha for assistance in running TITAN on our simulated data This work was supported by a US National Institutes of Health (NIH) grants R01HG007069 and U24CA211000 and US National Science Foundation (NSF) CAREER Award (CCF-1053753) to B.J.R implemented the algorithms and performed the analyses Peer review information Nature Communications thanks the anonymous reviewers for their contribution to the peer review of this work Publisher’s note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations Download citation DOI: https://doi.org/10.1038/s41467-020-17967-y Anyone you share the following link with will be able to read this content: a shareable link is not currently available for this article Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research as the man killed early Sunday in a drive-by shooting in south Oklahoma City Galaviz and three other men were standing outside a residence on SE 43 west of High Avenue about 1 a.m Sunday when someone drove by and opened fire Witnesses told police two black men and two Hispanic men drove by in a white 1990s Chevrolet Suburban sport utility vehicle and fired shots at the victims The SUV had a blue stripe or panel on the bottom Wardlow said she couldn't say whether police recovered guns or drugs at the scene She said the possibility the shooting was gang-related is being investigated Police ask anyone with information to call the homicide tip line at 297-1200 Callers may remain anonymous and may be eligible for a cash reward US EditionUK EditionScottish SunIrish SunSearchMy Account Dana White loved Andre Lima’s reaction to the disappointing end to his fight at UFC Vegas 89 The Brazilian flyweight made his Octagon debut opposite countryman Igor Severino on the undercard of Rose Namajunas vs Amanda Ribas in Las Vegas During a seemingly innocuous wrestling exchange midway through round two Lima began yelling and signalling to veteran referee Chris Tognoni In an incident that evoked memories of Mike Tyson's 'bite fight' against Evander Holyfield in 1997 Severino was subsequently disqualified for biting his opponent The UFC commentators wondered aloud if the bite was accidental before Lima lifted his arm and showed the deep teeth marks Severino had left on his bicep and Laura Sanko all let out audible gasps after seeing the damage before agreeing that Tognoni had made the right call “Those were two up-and-coming undefeated fighters,” he told Kevin Iole. “If you get frustrated and want out of the fight, there are plenty of ways to do it. But the worst thing you can do is bite your opponent."Now, you get cut and lose the biggest opportunity of your life. Not to mention, he’s going to have real problems with the NSAC.” As Severino’s night went from bad to worse, Lima headed to a local tattoo parlour to get a permanent reminder of his weird first fight in the UFC. The UFC CEO was planning to give Lima a bonus anyway but he decided to double it after being impressed by his reaction to the ordeal “I was going to give him $25k,” White wrote alongside a picture of Lima’s tattoo on social media Lima wrote on his Instagram page: “It was so insane I had to make it permanent Despite not getting a highlight reel KO win the 25-year-old enjoyed a pretty perfect debut as he improved his record to 8-0 made a fan out of his new boss and earned a massive bonus Lima will celebrate for a little while before getting back in camp and preparing for a second UFC fight that will hopefully end in less controversial circumstances For exclusive MMA videos and interviews, follow the new talkSPORT MMA YouTube channel here ExpandMembers of the Streator 12-Year-Old All-Stars pose with their District 20 championship banner after defeating Ottawa American 5-0 on Sunday PERU – Through the opening scoreless four and a half innings of Sunday’s Major League Baseball District 20 championship game at Washington Park’s Bill Burris Field the Streator and Ottawa American 12U all-star teams struggled to get much going Streator finally found a way in the bottom of the fifth Ben Mascote’s double to start the inning sparked a five-run rally for Streator before he finished his complete game by striking out the side in the top of the sixth to put the finishing touches on a 5-0 victory and a trip to the state tournament at Sterling next weekend Streator wrapped up the tournament going 4-0 [ Photos: Streator vs Ottawa American 11-12 year old baseball championship ] “I was able to put my curveball on the outside corner a lot today,” said Mascote, who finished allowing just three hits, no walks and 11 strikeouts on 68 pitches. “I was trying to throw my fastball on the inside and then use my curve to hopefully get them to chase. I felt like I hit my spots really well today.” Ottawa American's Jack Markey catches a fly ball in the sun against Streator All-Stars during the District 20 championship game on Sunday, July 14, 2024 at Washington Park in Peru. (Scott Anderson) Mascote’s aforementioned double off Ottawa American starting pitcher Rocco Affrunti landed just inside the left-field line to start the outburst. “I had the mindset going up for that at-bat that I already had two strikes on me,” Mascote said. “I just wanted to make sure I swung at a good pitch. I got a pitch middle-in and was able to put the bat on it.” Then, after an out, Noah Rodriguez smacked an opposite-field liner to right that fell just out of the fielder’s reach to plate Mascote with what proved to be the game-winning run. “Oh yeah, that was me,” Rodriguez said after being reminded of his run-scoring double. “It was an outside pitch, and our coaches had just talked about concentrating on hitting the ball wherever it was pitched. I really wasn’t thinking about anything but that. I just wanted to see the ball and hit the ball. “Ben (Mascote) was as good as it gets for us on the mound. It seemed like whatever pitch in whatever location was called, he put it right where it needed to go.” Zae Moton followed with a double to left to move Rodriguez to third. After Joey Studnicki walked the load the bases, Bradley Matsko had a two-run single up the middle to make it 3-0. Marshall Volkman followed with a line-drive, two-run single to left to end the scoring. Streator All-Stars pitcher Ben Mascote fires a pitch to Ottawa American during the District 20 championship game Sunday, July 14, 2024, at Washington Park in Peru. (Scott Anderson) “Ben was as good as it gets for us on the mound. It seemed like whatever pitch in whatever location was called, he put it right where it needed to go.” Affrunti finished allowing seven hits and a walk, while striking out two. Donovin Dilley recorded a pair of strikeouts in relief and earlier in the game made a perfect throw from center field in the top of the fifth to get a runner going to third. Ottawa American received singles from Ethan Farabaugh, Mason Collins and Kentley Smith. Streator’s Brody Daugherity recorded a pair of singles. “Rocco pitched very well for us today. We couldn’t have asked much more from him,” Ottawa American manager James Markey said. “He was really solid, but so was their guy, and they just battled each other from the start. “It was going to come down which team could put the ball in play the most, and Streator was able to do that in the fifth. They found some holes and were able to move runners around. We just couldn’t seem to get anything going with the bats today, but credit [Mascote], he pitched a very good game against us.” Ottawa American pitcher Rocco Affrunti (top) reacts after striking out a Streator All Star player during the District 20 championship game on Sunday, July 14, 2024 at Washington Park in Peru. (Scott Anderson) Copyright © 2023 Shaw Local News Network This website is using a security service to protect itself from online attacks. The action you just performed triggered the security solution. There are several actions that could trigger this block including submitting a certain word or phrase, a SQL command or malformed data. You can email the site owner to let them know you were blocked. Please include what you were doing when this page came up and the Cloudflare Ray ID found at the bottom of this page. ExpandThe last mold team at Owens-Illinois in Streator poses for a recent photo. They are (left to right) Eugenio Mascote, Nick LeBeau, Randy Hatcher, Ryan Lohr and Rafael Mascote. (Bill Freskos) Mike Zavada spent decades working alongside generations of co-workers at Owens-Brockway Glass Container Inc. in Streator. After more than a century of glassmaking, the Owens plant closed, putting an end to its local operations and displacing 152 workers. Zavada, who spent more than 60 years at Owens-Brockway, knows the plant was more than just a provider of jobs to Streator, but also a part of its identity. “You knew everyone by name,” Zavada said of his co-workers. “There’s a lot of history here, and it’s hard to see it go.” “At one point, there were over 3,500 people working here,” said the lifelong Streator resident. “By the time I retired, that number had dropped quite a bit. We used to run 10 tanks. By the time I left, we were down to just two. It’s been slowly declining and I saw it all happen.” The city, which once boasted multiple glass factories, now has none. The Owens plant has long been a key part of Streator’s history and identity, and the glass industry provided generations of families with steady work. At its peak, the plant employed thousands, contributing to Streator’s reputation as the “Glass Container Capital of the World.” Streator Historical Society Board President David Reed said the rise of the glass industry in Streator can be traced back to the area’s unique natural resources and strategic location. “The glass industry became our bread and butter,” Reed said. “As the mining industry started to wind down, we had everything we needed: coal for heat, a railroad system for transport, and silica sand from Ottawa.” In its heyday, the city had multiple glass factories, including the Owens-Illinois plant, which was built in stages beginning in 1909. According to Reed, while the Owens plant expanded significantly between 1929 and 1935, Streator was home to several other glassmakers as well, including Streator Flint Glass and Thatcher Glass. At its peak in the mid-20th century, there were more than 3,000 employees across four factories. “The 1940s and 1950s were really the peak years,” Reed said. “There were a lot of factories operating, and a much higher percentage of the town worked in glass than in later years.” For Rafael Mascote, a more recent Owens employee, the connection to the glass industry also was personal. Mascote worked at the plant for nearly 10 years as a mold maker, and was inspired to work there after hearing stories about the plant from his father, who immigrated to the U.S. from Mexico in the 1960s in hopes of working at Owens. “I grew up hearing about the plant. My dad had a brother who worked there, but he never got the job himself,” Mascote said. “So when I was looking for work, I thought, why not apply? I ended up getting the job in 2015.” Like Zavada, Mascote witnessed significant changes during his time at Owens. When he started, the plant still was focused on producing beer bottles, but over the years, the product mix shifted toward liquor bottles. At one point, nearly all four production lines were dedicated to the liquor market, though by the time of the plant’s closure, beer bottles had made a resurgence. Mascote, who was part of a new generation of workers brought in to replace retiring employees, remembers how challenging it was to learn the trade as the factory transitioned to making more intricate bottle designs. However, he found the work fulfilling, especially when it came to building relationships with his coworkers. “It’s the people you work with that makes it all worth it and gives good memories,” Mascote said. “The camaraderie, the teamwork, I think that’s what I’ll miss the most. The pride all of us took in our job was special.” Owens-Brockway, part of the global Owens-Illinois company, informed the state of Illinois in late October it would be halting commercial production at its Streator plant by Nov. 18. (Derek Barichello) simple character or mascot does more than provide a recognizable face for a company It humanizes the brand and gives fans looking to purchase a service or product a point of connection yesterday’s brand mascots have become today’s virtual influencers now have their own social media profiles where they connect to fans directly and serve as the first touchpoint for the brand Virtual spokespersons provide the best of both brand mascot strategies and virtual influencer marketing They retain the brand’s classic mascot image while capitalizing on a modern virtual influencer’s high engagement rate they never risk scandals or “aging out” of their roles While Flo from Progressive may one day retire the GEICO Gecko will continue to connect with audiences for decades to come we’re exploring five iconic brand mascots who became virtual influencers that reinvigorated the company's online presence KFC had a unique idea: transform their beloved Colonel Sanders into a young The new Colonel revitalized KFC’s social media presence, making appearances with other notable virtual influencers such as Dagny from The Diigitals and Imma from Aww Tokyo Like any other influencer (real or virtual) the Colonel used his platform to promote products His signature hashtag “#secretrecipeforsuccess” is also a clever While the virtual influencer Conel is no longer active sexy Colonel Sanders has continued to appear in creative campaigns such as an anime-style dating simulator and a short Lifetime romance movie starring Mario Lopez as the new Colonel Another classic brand mascot who transformed into a virtual influencer is the GEICO Gecko. In our article about the famous reptile’s history we explain how the idea was born out of the simple mistake fans would make by mispronouncing GEICO as “gecko.” Fast forward 20 years and Martin (the Gecko’s first name) is now an advertising icon who has starred in over 150 commercials GEICO elevated the character by creating an Instagram account for the Gecko breathing new life into their online presence Followers and fans alike are now able to see this brand mascot in a casual light as he uses Instagram like any other person such as by sharing his homemade sourdough bread or a funny meme: The very first Barbie doll was released over 63 years ago in 1959 by Mattel. But today’s Barbie is no longer just a doll She’s a cultural icon and an invaluable character IP for the toy brand she began her “Barbie Vlogs” series and officially became a virtual influencer on YouTube Her videos give advice to her younger fans about how to handle life’s challenges and encourages them to be confident in themselves While the Barbie of the mid-1900s may have been known for promoting unrealistic standards of beauty 21st century Barbie has re-shaped her image into an excellent role model for her new generation of fans on YouTube Of all brand mascots, CB has undergone the most significant transformation one of the largest retail chains in Brazil similarly to how virtual icon Lu represents Magazine Luiza The image of a young boy with a signature pirate hat known as Bahianino was used by the brand for decades he transformed into the virtual influencer we know today: CB represents the Casas Bahia brand to over 10 million followers on social media He brings his own unique Gen Z flair by incorporating trap music brand mascots helped companies stand out on store shelves they stand out on social media where many consumers spend most of their time These new virtual mascots can outlive any social media platform and continue to represent their brands for decades to come If you’re a brand with a mascot, there’s still time to make the jump to social media, giving your mascot (and, in turn, your brand) new life online. If you are an established brand curious about creating a virtual influencer from an existing character, contact us for more information on the process—we’re here to help Type your email to view this free insights piece Subscribe to get our insights in your inbox She has loved virtual humans like Hatsune Miku since she was 13 Her years of writing and research are driven by her desire to understand how people connect with others virtually and what the future of self-representation online will look like is a girl who welcomed athletes and fans from around the world making her the first Paralympic mascot ever to have a visible physical disability Petra played an important role at the Games cheering on thousands of athletes who competed between 3-14 September 1992 who is also known for creating the Barcelona 1992 Olympic mascot Cobi and the EXPO 2000 mascot Twipsy Mariscal is an expert in product and industrial design and was selected to create the Olympic and Paralympic mascots following a design competition The design of Petra features Cubist art techniques while the designer also said he was inspired by a drawing by his daughter that “worked perfectly and explained the concept” of creating a mascot with long legs and no arms Mariscal has hoped that Petra would leave a legacy in the host city in addition to showing his respect for Lorenza Böttner a Chilean-German artist who underwent amputation of her arms as a child one day Lorenza Böttner came to the studio and said We then held a press conference to show how she went about her daily life,” the designer recalled Back in 2007, it was impossible to know that Android was going to blow up and become as huge as it is today. In fact, for quite some time, it was impossible to know if Android even existed, as Google kept quiet on the flood of rumors until it came time to officially unveil the mobile OS we imagine many things about Android changed and today Google’s Dan Morrill is giving us a look at a canned Android mascot he thought up in the rush before the company launched the first iteration of the OS we all know and love today Believe it or not, that guy you see above was almost Android’s mascot – a far cry from the Bugdroid that has worked its way into out hearts over the years. Morrill explains the creation of these robots, which have come to be called Dandroids, on his Google+ page these Dandroids were born out of a last-minute need to have a mascot for the internal developer launch of Android: but I took a much-needed break of a couple hours and spent some quality time with Inkscape to create these… things we were prepping for an internal developer launch (meaning we were going to ask Googlers to start fooling with the APIs and give us early feedback) and I had no eye candy for the slides we were putting together Even though the Dandroids experienced a period of popularity around Google’s offices that all came to a screeching halt when Irina Blok introduced the Bugdroid which would ultimately become Android’s mascot We have to be honest and say that we like ol’ Bugdroid a fair bit better than these Dandroids but it’s interesting to learn that these guys were almost the Android mascots nonetheless It would seem that Morrill put a significant amount of work into these as well Morrill says he found these images while cleaning out an old NAS so perhaps there are more fascinating tidbits from the early days of Android hidden away on that server let us know what you think of these Dandroids All I have to say is that was a close one… I kinda like the clever “Dandroid” name “It would seem that Morrill put a significant amount of work into these as well” and website in this browser for the next time I comment Δdocument.getElementById( "ak_js_1" ).setAttribute( "value" This site uses Akismet to reduce spam. Learn how your comment data is processed 2019 at 8:37 am CT.css-79elbk{position:relative;}This Joliet man now faces five criminal charges IL - The following people are the latest new inmates at Will County's Jail arrested by Will County Sheriff's Office on residential burglary charges arrested by Illinois State Police on narcotics charges arrested by Will County on charges of delivery of a firearm with no valid FOID arrested by Joliet Police on four charges of possessing drugs with intent to deliver them and one charge of possessing drug paraphernalia arrested by Will County Sheriff's Police on domestic battery charges remanded from court related to his 2017 criminal charges of criminal damage to a school arrested by Wilmington Police on domestic battery charges arrested by Will County on two charges of theft and one charge of burglary Pair of red triangular Phryges meant to represent floppy conical hats linked to French Revolution France’s mascots for the 2024 Olympic Games have been likened to a giant “clitoris in trainers”, with the French newspaper Libération hailing it as a revolutionary departure from the traditional phallic symbol of the Eiffel Tower When the two triangular red mascots, the Phryges were unveiled for the Olympic and Paralympic Games they were presented as the shape of Phrygian caps conical hats associated with the French Revolution The Paris organising committee said it was an opportunity to “embody the French spirit by offering something new” in a break from the traditional animal figure often chosen for the Olympics Read moreHe said “from an anatomical point of view” having a clitoris as the French Olympic mascot was “very good news” and meant that after years of taboo and lack of education the country had collectively “at last understood what one looks like” it’s not a bad thing that Paris lets go of its eternal phallic Eiffel Tower” in favour of a clitoris a new representation of the French capital that is “revolutionary and feminist” But in the inevitable social media debate around the clitoris-shaped mascots one secondary school teacher said their simplistic triangular design could reinforce society’s vague notion of the under-discussed part of the female anatomy suggesting biology teachers be brought in to redesign them Julia Pietri, a feminist writer and publisher who led a street-art campaign for more eduction on the clitoris said of the Paris mascot comparisons: “I find it amusing because I campaigned for a long time to raise awareness of the anatomy of the clitoris people can at least recognise the clitoris It shows it’s now in popular culture and that’s a win.” MascotaSISA: the club’s mascot!We welcome a new member of our red and white family SISA is a funny fly who lives at Mosquilivi and she is going to be around the stadium cheering for our team playing with the fans and annoying those who don’t cheer for the team Flies are closely linked to the history of the city of Girona and the Saint Narcís legend too It represents the defence of the city and the hope that a teamplayer and a fighter when defending the city and the team characteristics of Girona FC which are very well represented with her while Girona was besieged by French troops a group of french soldiers entered in Sant Feliu’s Church with the intention of destroying the bishop’s tomb large flies came out of his body and they attacked the French soldiers and their horses causing many deaths and making them run away from the city The fly of Sant Narcís represents this defence of the city and the fighting spirit The club began a survey to choose their new mascot where the members had the final decision A first survey was launched to choose which city legend would represent the mascot The fly of Saint Narcís was the clear winner with more than a 55% of the votes The club members decided that it represented the club and the city better than the other two legends the ‘lleona’ and the ‘cocollona’ It was time to name the mascot and the members had the opportunity to propose a name The majority part of the proposals were aligned with the name of SISA and therefore this is the name our mascot was called SISA will perfectly represent the values and feelings of the club and the city of Girona She will be another fan of the club and will cheer for our team to lead us to the victory Aydenn Mascote-Otero out-spelled all other comers on Friday morning as the Polk School District held their annual Spelling Bee at the PCCCA Mascote-Otero is a 6th grade student from Cedartown Middle School and was the alternate winner to take the top prize for the District Bee He will go onto represent the Polk School District in the Regional Spelling Bee on February 24 Rockmart Middle sent Graham Dooley and alternate Gavin Hendrix and Cedartown Middle also saw Febe Perez Tomas as a winner as well Check out additional photos shared by the Polk School District below: The District posted the results of the Bee on social media today as well Polk County’s Rotary Club sponsored the 2024 Spelling Bee for the Polk School District They thanked the caller and judges Andrea Sorrells and Rebecca Crymes for taking time out to provide their services for the Bee Comment * document.getElementById("comment").setAttribute( "id" "aeee769f2806949f99160d5f03bc2d38" );document.getElementById("dd5b412ef0").setAttribute( "id" Myrick Multimedia LAS VEGAS, NEVADA — Mixed martial arts (MMA) tattoos are getting even weirder UFC CEO, Dana White, immediately cut the 20-year-old Severino from the promotion and then rewarded Lima with some extra money as the first — and hopefully very last — “I got bit bonus." Lima emerged from the absolutely strange circumstance as a new star for how he handled the unfortunate situation he went to a local “Sin City” ink shop and got a tattoo of the bite impression .. Andre Lima got a tattoo of his bite pic.twitter.com/KMN4lRtLXN A post shared by Mascote (@andremascote__) White saw Lima's insane bite tattoo and gifted Lima even more money A wild turn of events gets commemorated …Lima already went and got a tattoo of the bite! pic.twitter.com/4kOXH6hc1Z Lima is undefeated (8-0) and one of the brightest young prospects to come off of season seven of Contender Series “Mascote” did not want Severino cut or fired from the UFC The legend grows For complete UFC Vegas 89 results, coverage and highlights, click HERE U of T mascot True Blue is a lovable critter with great moves Read More and even among robed graduates at Convocation Hall you’ll often spot a bright blue beaver wearing Varsity gear Meet True Blue: the official mascot of the University of Toronto and Varsity Blues The lovable critter with great dance moves attends plenty of campus events but he also appears at community functions such as the CIBC Run for the Cure Two work-study students alternate wearing the suit They undergo an audition process to test their theatrical and dance skills – and their inner class clown The identities of these students remain a well-guarded secret featuring a slimmer and more modern design that is easier to see out of His new look debuted at the Varsity Blues football home opener on August 30 Free shipping to mainland Portugal and the islands Deliveries in mainland Portugal between 24 and 48 working hours after payment confirmation 30 days for exchanges and returns from the moment the order is received