Apologies for not getting to this earlier. Our in-house GC is est fit to answer this; however, as far as I am aware, CLIA only requires that we keep samples until the analysis is complete and results are returned to patients. They recommend that one keeps this as long as possible. The other thing is the difference between a report and raw data. I believe that we are supposed to hold onto reports for 21 years, some states have slightly different regulations but that's different from raw data. We are also a physician-ordered LDT while 23andme is FDA approved so there are differences there as well.
Great question and something that I should have clarified. We look for mutations that are either considered pathogenic or likely pathogenic under the guidelines of the American college of medical genetics and genomics when considered with the other medical history of the patient. This is what we return to patients. This is considerably different than a "risk score" as you have pointed out. Other companies, like Color, use the physician ordered model to offer that sort of information for cancer risk and cardiovascular conditions. We focus on primarily on mutations associated with rare conditions. In principle, we could offer these other things as our test captures much of that information and we are looking to add this to the analysis in case patients are interested.
I think this is really well put and something that we haven't considered (letting users download their data and then re-upload later). As long as we could ensure the data hasn't changed it could work. Unfortunately, we can't do anonymous testing because it is physician-ordered. I should say that some of this identifiable information is super important for the analysis.
Really appreciate it! As a quick comment, we work with a physician network that has physicians licensed in all 50 states and they review the medical information of all of our patients. This way we don't put the burden on our users.
YC was immensely helpful for us in a lot of ways. Definitely happy to go into more detail offline but two things I really liked were that there are so many companies in the healthcare space now that have come out of YC and regulation is a hugely scary aspect of the field and getting advice from them on how to navigate many things saved me so much time and headache. YC also very much redefined how I personally think about an MVP and it's usually a lot more minimal than I initially realise. As the community grows bigger, a lot of this will become even better. I almost wish we were slightly further along when we started as a lot of the prolems that companies in our batch were facing are starting to affect us now that we're not in set-up mode. The key thing for me is that we have to make sure we do right by patients above all and I have to integrate that with all of the other advice that sometimes conflicted in my head.
Really great suggestion. We haven't tried accepting this yet but naively, I would imagine they should be. I wish I could give a more concrete answer but I will further look into the details and ask our in-house GC.
So it's important to note we don't test for diseases but rather variants which may be the etiology. I'm not an expert in this condition by any means but a quick search says we still don't know the candidate genes for this and many have been excluded which would be problematic for our test.
It sort of determines how the FDA chooses to regulate. This was one of the issues that came up with 23andme in the beginning. The FDA chooses not to strictly regular physician-ordered lab-developed tests and thus the physician-ordering is sort of a key piece. Right now, we only accept saliva (and soon a cheek swab) that's sent in via one of our kits. Unfortunately, at the moment, we are not exploring doing sequencing on other samples.
At the moment, we are currently outsourcing genetic counseling. We simply don't have the capacity at the moment to bring that in-house. Very happy to discuss further over email (harley@probablygenetic.com). One thing to consider is that for many of these other companies that are doing genotyping or panels, a lot of the analysis can be automated. For exome and genome testing, this is not currently the case and there is plenty of space to develop IP in that regard.
Invitae is definitely one of the most impressive companies in the entire genetic testing space. There are many companies that can offer exome testing, but as far as we are aware, in almost all other cases, you still need your own physician to order and you would be surprised how many patients struggle to get their doctors to order genetic testing, especially because in many cases insurances are not reimbursing. Our test is in CLIA-certified and CAP-accredited lab and is physician-ordered. It's important to note that we do not make medical diagnoses we simply provide the report that you can take to your doctor and have them interpret in the context of your other medical history and information. In essence, it's a very similar service but in our case patient-initiated. The report is signed out by a clinical lab director in connection with our sequencing and bioinformatics partners.
Great question. Right now the major difference is the D2C (patient-initiated, physician-ordered) aspect. Invitae is starting to offer this to some extent but they mainly seem focused on cardiovascular and cancer. Unlike those companies, we don't consider ourselves a testing company. For most patients in the rare disease space, understanding the underlying genetic cause is really only the first step in the process and then most need tons of help navigating the healthcare space afterwards. We started with the test, mainly because of the access and affordability issue patients were having. Many of our patients have requested tools for longitudinal phenotypic data collection, connections with all of the relevant advocacy groups, further genetic counselling, efficient ways to test family members, and detailed, patient-readable information content about their variant. We try to provide everything these patients need (aside from medical advice of course) as the healthcare system isn't currently set up to help rare disease patients.
Yes, we do allow users to access their raw DNA. We will make VCF, BAM, and FASTQ files available if requested. We map the entire exome at 100x coverage which covers all genes.
Thanks so much for the comment. That's a really great way to describe the distinction! In terms of genetic counseling, for post-test purposes, we won't release positive results until the patient has booked a session with one of the genetic counselors where the results are released. In the case of negative results, we give the patient the option to discuss with a counselor but do not make it mandatory. In both cases, the counseling is included in the cost of the service. For pre-test counseling, the way it currently works in our service is that when users request a test, they have to fill out a detailed medical intake questionnaire which is then reviewed by both a genetic counselor and a physician. Right now, it is up to the discretion of the genetic counselor that reviews the information whether they feel like they should reach out to the patient and discuss how this may impact them or whether they have requested the appropriate test. If demand increases significantly for pre-test counseling, this is definitely something we will able to add moving forward.
I think that's a really good point. In fact, for many lab tests where the results are completely "cut-and-dry", this suggestion totally makes sense. For us, one thing we consider is that the diagnostic yield for these types of sequencing tests is only ~40%-50% in the best case. We know from the literature that if we perform a reanalysis 6 months-1 year, the chances that we find something in patients that don't have a result increases quite substantially as does how we interpret known variants. Thus, continual reanalysis is very important to many of the patients that we work with. Unfortunately, it's too expensive to resequence every time we need to run such a reanalysis algorithm.
Thanks so much for the comment! In order to offer this testing and give back a result report that can really be used by a doctor, it should be physician-ordered, processed in a CLIA-certified and ideally, a CAP-accredited lab, have the lab report signed out by a clinical lab director, and ideally (for ethical reasons) offer genetic counseling to patients. From the bioinformatics perspective, the bioinformatician should be trying to take in all of the medical information we know about the patient and apply this to the analysis. This is what we offer. In contrast, with Dante labs, you basically send them your sample and get back raw data and some very basic reports. If you bring these to a doctor, the recommendation might be to just get another genetic test via a lab that follows all of the procedures as stated above so a person may end up doing it twice if they go that route. Ours offers the complete end-to-end solution that you would get in the healthcare system while Dante labs is really just a way to access your raw DNA.
Great question. We use a CLIA-certified and CAP-accredited lab, and we must keep the specimen through the completion of the testing and result reporting. If there is any sample remaining after testing, we will hold onto it longer in case we need to run a validation or other tests as recommended, but we will, of course, have it destroyed at the request of the patient. It's recommended that we keep them for as long as they are stable.
Based on the total flux, and photometry, usually they will assume a model for the star formation history. Sometimes a single burst, a constant star formation rate, an exponentially declining star formation rate, or maybe a combination of multiple bursts. The strength of the Balmer Break and the UV slope can be good indicators but even in this case, there are large uncertainties. I haven't read the paper but this is how it's often done in general. Of course, the type of stellar populations you use, impacts from dust, and the fact that star formation histories are rather complicated can impact accuracy.